Tag Archive for: MRD Testing

What Is MRD-Positive Acute Myeloid Leukemia?

What Is MRD-Positive Acute Myeloid Leukemia? from Patient Empowerment Network on Vimeo.

What do acute myeloid leukemia (AML) patients need to know about MRD-positive AML? Dr. Catherine Lai from Penn Medicine discusses minimal residual disease (MRD). Learn about the meaning of MRD, complete remission, and MRD testing methods.

[ACT]IVATION TIP from Dr. Lai: “Ask if MRD testing can be done on your bone marrow biopsy at the time at which you or after you’ve had your chemotherapy.” 

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See More from [ACT]IVATED AML

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AML Clinical Trials Critical to Treatment Breakthroughs and Improvements

Transcript: 

Art:

Dr. Lai, what is MRD-positive AML?

Dr. Catherine Lai:

So, that’s a really good question. And to answer that question, I’m going to actually answer a different question, which is, What is the definition of complete remission? So the definition of complete remission is when we do a bone marrow biopsy, and we have less than 5 percent of those blasts or leukemia cells in the bone marrow, and that is also in the setting of a relatively normal immune system or normal other blood counts have improved, so that your neutrophil count is above 1,000, and your platelet count is above 100,000. So, MRD, which stands for measurable residual disease, means that you’re in complete remission, so you have less than 5 percent blasts, but you’re more than zero.

And we, in general, when patients who are MRD-positive, we know that if you were to do nothing, that those patients have a high likelihood of relapse. We know for the patients who are going to transplant, if you’re MRD-positive before transplant, those patients also have a higher likelihood of relapsing after transplant. And so we tend to monitor it if possible…the tricky thing is, is that there is not a standard way to measure MRD testing as of yet, the common approaches are right now are with either flow cytometry or with PCR or next-generation sequencing, if you have a particular targeted mutation that we can follow.

So your activation from that standpoint is to ask if MRD testing can be done on your bone marrow biopsy at the time at which you or after you’ve had your chemotherapy. 

How Do Lung Cancer Patients Benefit From MRD Testing?

How Do Lung Cancer Patients Benefit From MRD Testing? from Patient Empowerment Network on Vimeo.

MRD testing is another tool in the lung cancer care toolkit. Expert Dr. Christian Rolfo from Mount Sinai explains how MRD testing aids in patient monitoring, use of liquid biopsies in patient care, and updates about immunotherapy for early stage lung cancer.

See More from Best Lung Cancer Care

Related Resource:

How Can Specific Biomarkers Impact Lung Cancer Progression?

How Can Lung Cancer Disparities Be Addressed?

Lung Cancer Treatment Landscape Overview


Transcript:

Dr. Nicole Rochester: 

There are a few questions from our audience that I would love to present to you, and so one of them comes from MacKenzie and MacKenzie asked, “Can you speak about MRD testing and what that means for lung cancer?”

Dr. Christian Rolfo: 

Yeah, and that we were discussing briefly. So minimal residual disease is the…as I say, when we have an operation, we can have the opportunity to have completely resected a tumor, but we don’t know more than with the CT scan when the patient will recover. So we are without an answer believing every follow-up visit what has happened, seeing if it has gone. So we are trying to reduce this…reduce the anxiety first of all, to try to get the tools that are able to identify patients that they can recurrence, have a recurrence so liquid biopsies, one of them, and we have now the several methods that are trials and several data coming that there are some companies that actually they are a market for some of the options, we are still having validations, required validations, but we will certainly be there very shortly in time to identify these patients and to treat them in the proper time.

Dr. Nicole Rochester: 

Wonderful, and I think you just addressed a question that came in from Harold, which was., “Is liquid biopsy playing a role in monitoring disease recurrence in lung cancer?”

Dr. Christian Rolfo: 

Sure, we are actually tailoring treatments and checking the patients, and I have several, several experiences in patients that they’re monitoring over the time, and we have actually some of the vendors that are proposing this approach monitoring, liquid biopsy is a great tool because it’s minimally invasive, it’s just a blood draw, and we can continue. Not all the patients have the possibility in terms of they are not all cheaters, that is something we need to know DNA, so it’s the majority of them, we can do it in some minimal proportion, we cannot do it when there are also possibilities to follow them.

Dr. Nicole Rochester:  

And our last question from the audience comes from Laura, and she wants to know, “Are  immunotherapy combinations in the metastatic setting, expanding to treat earlier stage lung cancer?”

Dr. Christian Rolfo: 

Yeah, absolutely, we have actually an FDA approval for us, one of the immunotherapeutic drugs in patients after the resection of the disease with some characteristics, but we are there and actually we are having more and more clinical trials using in earlier stages so we will say in the other stage from the earlier stage from that is the neoadjuvant, and we call that when we are doing a treatment to reduce two months to be operated later on, so we have also some trials that are going there, but we have an approval already for the adjuvant setting that is after the surgery in some patients. 

Dr. Nicole Rochester: 

That’s wonderful. You’ve given us a lot of good news. A lot of hopeful news, Dr. Rolfo, it is time for us to wrap up. I want to thank you again for being here for sharing your expertise. 

How Can I Get the Best Lung Cancer Care?

How Can I Get the Best Lung Cancer Care? from Patient Empowerment Network on Vimeo.

How can lung cancer patients access optimal care? Expert Dr. Christian Rolfo from Mount Sinai and Dr. Nicole Rochester discuss the latest lung cancer treatments and research, lung cancer testing, equitable care, and patient-centered care for the best health outcomes.

See More from Best Lung Cancer Care

Related Resource:

Lung Cancer Treatment Landscape Overview

How Do Lung Cancer Patients Benefit From MRD Testing?

What Are the Latest Lung Cancer Treatment Updates?


Transcript:

Dr. Nicole Rochester: 

Hello and welcome. I’m Dr. Nicole Rochester, I’m a pediatrician, a professional health advocate, and your host for today’s Patient Empowerment Network program. We are so happy that you tuned in. How can you access the best possible lung cancer care? What do the latest combination therapies mean for you? Should you consider a clinical trial as a path to enhancing your lung cancer care? This Best Lung Cancer Care program focuses on providing actionable steps to achieving equitable care and connecting to patient-centered care on your path to empowerment. We are joined today by international lung cancer expert, Dr. Christian Rolfo, Professor of Medicine and Associate Director for Clinical Research in the Center for Thoracic Oncology at the Tisch Cancer Institute. Thank you so much for joining us today, Dr. Rolfo.

Dr. Christian Rolfo: 

Thank you, Dr. Rochester, for having me. It’s a pleasure to be here. 

Dr. Nicole Rochester: 

Wonderful. I’m looking forward to our conversation. Now, following this program, you will receive a survey and we would be thrilled to get your feedback because this helps inform future lung cancer programs we produce. Please remember that this program is not a substitute for seeking medical care, so please be sure to connect with your healthcare team regarding the best options for your care. Now, let’s delve into this very important topic, how can I get the best lung cancer care? And, Dr. Rolfo, we’re going to start with an overview of the lung cancer treatment landscape. We know that this landscape is rapidly changing and keeping up with the pace of developments could be a challenge not only for doctors, but certainly for patients and family members, so I was hoping that you could give us an overview of the current lung cancer treatment landscape.

Dr. Christian Rolfo:

In the last year, lung cancer treatment was changing radically. We have actually, including some of their new concepts as precision medicine or personalized medicine, that we have actually different therapies that are specifically for some group of patients, that they have specific alterations in their tumors. And when I’m talking about alterations I refer to mutations, genomic alterations that can be targeted nowadays with specific medications, and currently, some of them are actually, the majority of them are actually pills, for example. So it was changing radically and we are not using it like before chemotherapy for everyone. Another area of important interest was the introduction of immunotherapy, this is also an important tool for fighting cancer, and there you have a substance that are administered generally, all of them are intravenous, and this is the principle of that is to await from your own inner system, from the patient immune system, they are the tools to fight against the cancer, so it’s a very innovative way to approach cancer, and this is.

The good thing is that these two approaches targeted therapies, immunotherapy, and also still obviously the combination with chemotherapy in some of the case with immunotherapy, we can use not only metastatic patients, so in patients who have advanced disease, but also we can use in patients who have earlier stage that they were operated, for example, and we want to prevent that this patient is not going to a further process of cancer metastases, or there are several, several innovations. Then we have innovations that are coming also from local treatments and we call local treatments the one that, for example, surgery or radiation, we have new technologies also that are arriving there, and the combination sometimes with the medical treatment or systemic treatments that are going everywhere that is the description of systemic are helping these patients to have not recurrence and improving. Actually, lung cancer survival was really improving in the last years, and we are very excited by that because, unfortunately, it’s very still an aggressive disease that we were able to change with all this armamentarium the prognosis of these patients.

Dr. Nicole Rochester:

Wow, that’s a lot. I mean it’s exciting to hear that there are so many new developments on the horizon and that so much has happened just in the last year as it relates to therapy. What have we learned about drug resistance as it relates to non-small cell lung cancer? Are there any new developments in that area?

Dr. Christian Rolfo:

Yeah, obviously the patients of the…as I just commented, we have different patients with different needs and different scenarios, so we are now fragmenting a lot of the diseases and we have actually different diseases, and one big disease that is the lung cancer, so now we are treating patients in a different way. And some patients have, for example, patients who are under treatment with targeted therapies, they can develop mechanics of resistance that we can nowadays not only identify but also treat. 

So we can treat and change the recurrence of these patients. One of the tools that we are using for that is liquid biopsy, for example, that is this blood draw that we are going for the patients, and actually, we are trying to do this determination from the very beginning and also monitoring the patients after we have this information to see if we are able to determine the mechanics of resistance, see also the outcomes of some of the therapies and change the treatment when it’s necessary. In immunotherapy, we have alterations that are resistant or refractory, that is another way of definitions so refractory we say patients that are not responding during the treatment and resistance of patients that or simply patients that are after the treatment having a progression in a very short time, so we need to identify these two categories and try to treat them in different ways that we have armamentarium for that as well.

Dr. Nicole Rochester:

Wonderful, thank you for that. So you’ve mentioned a lot about updates, are there any other exciting updates that patients and families should know about related to lung cancer, maybe things that are in the works that we may hear about in 2023?

Dr. Christian Rolfo:

Yeah, I said, for example, liquid biopsy I was mentioning liquid biopsy, and we are focused obviously, and in patients that have advanced disease or when they have this disease that is already confirmed. But we are now moving the tools that we have to the dedication of cancer using liquid biopsy from the very beginning, so we can use a minimal residual disease that is patients after the surgery. And I think I hear answering one of the questions that we have in the chat that this minimal residual disease is the quantity of two more that sometimes we are not able to see in the images or is very tiny, and we have equivocal information, the possibility to discover the patients that after surgery, have the possibility to recurrence or have come back of the disease is really important. 

And also we are looking for early detection of lung cancer trying to identify patients with the high-risk populations that they are maybe having the opportunity to be in lung cancer screening because they are smokers, or because they have all the characteristics on top of this model that we can also use the liquid biopsy there. But one of the most important messages that I want to say, because I mentioned it here smokers and I want to remind you that we have a big proportion of patients around 20 to 25 percent of the patients that they never smoked and that they can develop lung cancer, so we have a motto, we say if you have a lung, you can have it because we want to break this stigma that lung cancer has the only patients who are smoking, obviously, smoking and tobacco are related highly with lung cancer. 

Dr. Christian Rolfo:

But also we have patients that are second-hand smokers or they have other causes of lung cancer, so we need to be aware and we need to try to get attention for that because, in this special population of non-smokers, we know that there is a special characteristic that we can treat them completely different, so it’s very important that we identify those patients as well.

Dr. Nicole Rochester:

I really appreciate you sharing that, Dr. Rolfo, because as I’m sure you know, there’s a lot of stigma associated with lung cancer and the assumption that if you have lung cancer, then that automatically means that you are a smoker, and not that we know that people who smoke, those are challenges, but to just acknowledge that not everybody with lung cancer is someone who is a smoker, and also that the approach, the treatment approach may be different, so I really appreciate you pointing that out.

Dr. Christian Rolfo:

And actually Dr. Rochester, you know this stigma was causing several domino effects. We have less funding for research, we have less support from the community sometimes like other tumors have, for example, breast cancer. So if we are looking specifically in lung cancer, the quantity of women that are dying or are going to a diagnosis of lung cancer, it’s very impressive, but actually it’s killing more people sometimes than other tumors. So we need to be very careful with this stigma because we need…and this is a call for action, now we need more funds, we need more support from the community, because this is a very important area that will need research.

Dr. Nicole Rochester:

Absolutely, so that brings me to the next section of our program, you’ve mentioned a lot of these therapies already, I just want to go a little bit deeper into exploring some of the lung cancer treatment strategies and also talk about clinical trials, so you talked about bio-markers. Can you expand a little bit on that? We know that no two lung cancers are the same. Can you explain to the audience how biomarkers help with lung cancer treatment and they can be so important? 

Dr. Christian Rolfo:

Yeah, we have different…as I say, we are looking at specific characteristics from the tumor when I’m referring to genomic alterations that I’m not referring to something that you can get from your family and bring to your descendants. So I’m talking about mutations that are occurring inside the tumors and only for the tumor, and so affecting only the subject that have this patient that has this alteration. So these biomarkers are an important way to identify populations that we can treat specifically, and I would like to be a little bit more specific on that. We have some of the alterations, for example, one of the mutations that we call EGFR or epidermal growth factor receptor mutation that is supported in different populations in different frequencies. 

For example, if we have patients that are with an Asiatic origin, we have there the possibility to have a…and I’m referring, for example, Chinese, Japanese, this area of the East Asia, we have a hyper-prevalence of these mutations in around 50 percent of the patients with lung cancer, non-squamous we’d say this is another characteristic of the tumor can have this specific alteration. If we are moving, for example, to Latinos, the pains of the areas of Latinos they are coming from, if you have Mexican or for example, Peruvian, they have also due to their ancestry, they are similar to the Asiatic population, 40 percent we’re going to white populations and Anglo-Saxons or Europeans, they have around 7 to 15 percent according to the different regions. 

African-Americans within 15 to 20 percent. So these kinds of alterations are giving us the opportunity to treat and we have nowadays inhibitors and that’s drugs that are from first, second and third generation, so we were evolving in January, this pharmaceutical in January to develop all drugs that are able to penetrate in the brain and acting not only in the tumor, but also in brain metastases. And patients who have this mutation, for example, are treated in first line, in front line, or the first treatment that they receive are pills, no chemotherapy. 

So for this reason, and that is something that is important because when we know that patients, when they start this journey of lung cancer diagnosis before they see an oncologist, they were struggling to get the diagnosis and then we’re passing through several doctors from the general practitioner or to the emergency room, going to CT scan and then a biopsy then a pulmonologist until they get the diagnosis, it’s a big period of time sometimes that we are very nervous because we want to each patient to have a treatment as soon as possible, and sometimes when they arrive to us, we say they need to wait until we have the results of these biomarkers.

So it’s difficult to understand, I put in the place of the patients and the families are really difficult to understand that I was passing a lot, I went here, I came here and I want your treatment right away, but this period that we are asking to wait is really important because we will have information that can change radically the treatment and the history of these patients. So one of the problems that we have in America is the lack of testing, so we have all the tools to test the patients, but if we are looking at some of the statistics, 50 percent of the patients have been tested…39 percent if we are moving to groups, for example, of African-Americans, so we need to be very careful that don’t push to get the treatment very quickly without having all the elements to this thing, which kind of treatment is the most adequate for the patient. 

Dr. Nicole Rochester:

That is such important information, and I really appreciate that, I appreciate it. That you put it in the perspective of the patients and family members. And that grueling, long wait, long time to diagnose this, and finally you’re in front of a specialist and the perception is that, Okay, now I’m going to get this treatment that I need, and then like you said to hear, now you have to wait a little bit longer, but also to understand that that wait is important to make sure that you get the treatment that is meant for your specific type of cancer, I think that is so incredibly important.

Dr. Christian Rolfo:

And believe me, we are trying to push as well from the that there are unfortunately technical times that we cannot overcome that are for testing and for having these results, and we can do that by like I said liquid biopsy, but also tissue biopsy, so we are sending the tissue that the patients gave for a biopsy in a biopsy or in a resection when they have surgery. We take these small biopsies and we send them for analysis and take longer sometimes, so it’s a pity, and we know but it’s the only way to go for the right treatment.

Dr. Nicole Rochester: 

So with regard to the biomarkers, you mentioned that these are kind of unevenly distributed among different populations depending on your origin, and so how does that play into the progression of the disease, what do we know about why patients with specific biomarkers have a different degree of disease progression?

Dr. Christian Rolfo: 

Yeah, so we know more or less that the characteristics, I mean more or less in terms of the evolution of the clinical characteristics of these patients, in terms of organ affection in case of progression, but what is most important of this is that we are able to continue to identify, and I say monitoring these patients with liquid biopsy for example, this is a good tool to understand or to understand it a bit better, which kind of mechanistic involvement. So because we have, for example, patients who were receiving the case that I was discussing before EGFR mutations and they received one graft from the very beginning, a third generation TKI is the one that is approved for the first line, and this patient has a progression.

 The possibility to have a mechanism of resistance is different, so we can have mutations that are coming in the same pathway, so in the same area, same kind of mutation, but different location, just to the people understand is the kind of line and we have the mutation that is here, the one that we are attacking, but we have another mutation that is in this area and it’s not covered by the track that is covering this mutation. 

Dr. Christian Rolfo: 

So we have nowadays drugs that are going to, in this area in clinical trials, or we have in other cases other areas of the task of mutations that have nothing to do with the original one. So we are activating another kind of pathway, or we are transforming the tumor from one kind of tumor to another kind of tumor, so for this reason, identify which kind of mechanism of resistance is in place can have an important or have important implications for how we are treating these patients, so we need to look at that to treat the patients.

Dr. Nicole Rochester: 

Wonderful. And speaking of resistance, we know that there are some patients who end up trying multiple therapies in order to treat their lung cancer, are there alternative treatment strategies for lung cancer patients who have failed all therapies? 

Dr. Christian Rolfo: 

Yeah, absolutely, we have research in lung cancer is never stopping in oncology generally, but in lung cancer it’s really exciting to see how this research is evolving and it’s arriving to the patients the meaning of the research when we are doing access to the patients, to the discovery of the finding that we have, and obviously, we have strategies in the clinical practice, but also we have the clinical trials. So clinical trials, and that is something we need to try to define very well because some patients believe that when we are going to clinical trials there are no more options or we don’t have any other options to do. We are sometimes using clinical trials even in the first line, so even in patients that are for the first time being treated. 

Because we know that some of the cases we are treating patients with from some standard of care and using drugs on top, we want to explore it, we can improve these outcomes that we already know. That could be also a clinical trial, that is also a clinical trial. So don’t take the participation in a clinical trial as the last option that you have, sometimes you will go to your doctor and the first time that you see a doctor for your first diagnosis, they can propose a clinical trial. 

And this is really valuable. What we really appreciate is the collaboration of the patients to be in clinical trials, because we need to remember that the drugs that we are using today were analyzing other patients before, so the treatment that you are receiving in a standard of care today were before a clinical trial, it’s really important how we can interact with the research and the clinical practice very easily, so we have also some options that are…for what we call early drug development, that there are some drugs that are in patients who are receiving the standard of care, and they have the opportunity to be treated in new drugs, and you can discuss…believe me there, and 

I know that there is a lot of questions about clinical trials but the clinical trial setting is really restrictive, it’s very well-coordinated, so you would be part of a very coordinated and structured things that they try to protect the patients in the first instance, and try to understand also how we can help the patients and the future generations. So that is really why we appreciate patients, that the contribution of patients that are giving to this clinical research because it’s helping to advance the knowledge for the new patients as well.

Dr. Nicole Rochester: 

And I really appreciate how you described clinical trials, and particularly your distinction about it’s not always this last-ditch effort that sometimes you all are using clinical trials as first line therapy. One of the common things is that clinical trials are tomorrow’s medicine today, and helping patients and families to understand that there’s value in being involved in clinical trials and that…and I think with COVID there’s a little more understanding, but certainly, we have a long way to go, and so I appreciate you sharing that. Do you have any specific examples of patients in your practice, and not names of course, but examples of…that have benefited from clinical trials?

Dr. Christian Rolfo: 

Absolutely, we have several of examples and actually FDA was doing a terrific job in the last year to try to get access quickly access to the drugs for patients, and some of this access that was granted was based in clinical trials that we’re starting for a phase one or phase two trials, so we are really doing a very rapid evolution of the drug development, and this is a revolution actually of the drug development because we have access very quickly. I can tell you that it was certainly in my career, several patients in clinical trials that they got benefits. Obviously, clinical trials are answering questions, so that is the way that we can answer questions scientifically and is the only way that we can advance in clinical therapeutics. 

Dr. Nicole Rochester: 

Wonderful. So I want to move into treatment access, we’ve talked a little bit today about some of the differences that we see in lung cancer with regard to the biomarkers, you and I know, and I’m sure that was in the audience, know that health disparities are widely reported here in the United States with really any all conditions, including lung cancer. So I’d love for you to talk a little bit, Dr. Rolfo about some of the challenges related to appropriate access to lung cancer care as it relates to different socio-demographic populations, and then how can we begin to address those disparities.

Dr. Christian Rolfo: 

Yeah, this is a topic that is really in my heart because I was coming with you before we start the communication, the recording of this. I was working in Europe before coming to the United States. I was shocked by the disparities that we see in some healthcare situations, so in my position before in Europe, we have a healthcare system that discovering for patients and we have, obviously, difficulties, but here I saw in some communities really underserved in terms of access to different service and healthcare is one of them. So we need to be conscious about that when we have patients that are struggling to get transportation, we have patients that are struggling to get approval for some drugs. 

So, there are a lot of areas that need to be addressed, disparity also in terms of language, we have also patients that are not understanding the doctors,  we have patients that are having difficulty when to get to the app information when we are saying, “Oh, you can see your report in your app,” so it’s not easy for some of them, we have generational gaps as well, these are disparities as well. So taking or being conscious of all these factors is making us take action and how we can take actions in our institutions, and in several institutions in the country, we have the support of an experienced team that is addressing that and teams are specific that are working for disparities. Some of them are social workers, some of them are advocate patients, so we have a big team of institutions that are helping to the patients to go for different scenarios, and even we have patients that are homeless, so how we treat patients in these conditions when we know that the patient is in a shelter, so if you have toxicity, what will we be doing. 

So all these things are taken into consideration, believe me, because it is like New York, you have a big disparity of or a big diversity, and we say of populations in one consultation morning, you can see all of them in your waiting room, so we need to try to address all this, and there are politics that are coming from us as a healthcare system, but there are also politics that they need to come from governmental politics, so try to use these…all the tools that we have at our disposal are important, and also we have a very good support of advocacy groups. 

Dr. Christian Rolfo: 

And this is something that I want to really profit their patient to say thanks because we have several, several advocacy groups that are doing a terrific job from testing to helping patients to go through this journey. So it’s really an important job, and obviously families, families are helping to these disparities and patients, so patients themself. So what I say always to the patient, raise your voice, empower yourself.

 Try to ask for your rights if you don’t understand your doctor… Ask again, if you want to have a second opinion, talk to your doctor, that is the most important thing. We are very open to help the patients, and that is our mission. So if I say to my patients, If you want to have a second opinion, please let me know, and I try to direct you to somebody who is an expert in the field and can help us to learn better your disease or your treatment, but I think it’s a situation that everyone is winning, especially the patient, but also ask for future patients understanding better every case.

Dr. Nicole Rochester: 

Well, as an independent patient advocate, myself, Dr. Rolfo, I always get super excited when physicians like yourself are talking about and emphasizing the importance of patients and families advocating for themselves, so I just want to reiterate a couple of things that you said just to make sure that our audience heard it very clearly and asking questions is one of the things that you said that is, I believe one of the most important ways that we can advocate for ourselves and for our family members in healthcare settings, and I really appreciate that you offer advice around second opinions.

A lot of people feel that they are sending their doctor if they ask for a second opinion, but a confident doctor like yourself and a good doctor is going to encourage that, particularly if the patient or family just needs that extra reassurance, so I just really appreciate that you brought that up. Before we wrap up, there are a few questions from our audience that I would love to present to you, and so one of them comes from MacKenzie and MacKenzie asked, can you speak about MRD testing and what that means for lung cancer?

Dr. Christian Rolfo: 

Yeah, and that we were discussing briefly. So minimal residual disease is the… As I say, when we have an operation, we can have the opportunity to have completely resected a tumor, but we don’t know more than with the CT scan when the patient will recover. So we are without an answer believing every follow-up visit what has happened, seeing if it has gone). So we are trying to reduce this…reduce the anxiety first of all, to try to get the tools that are able to identify patients that they can recurrence, have a recurrence so liquid biopsies, one of them, and we have now the several methods that are trials and several data coming that there are some companies that actually they are a market for some of the options, we are still having validations,  required validations, but we will certainly be there very shortly in time to identify these patients and to treat them in the proper time.

Dr. Nicole Rochester: 

Wonderful, and I think you just addressed a question that came in from Herald, which was is liquid biopsy playing a role in monitoring disease recurrence in lung cancer?

Dr. Christian Rolfo: 

Sure, we are actually tailoring treatments and checking the patients, and I have several, several experiences in patients that they’re monitoring over the time, and we have actually some of the vendors that are proposing this approach monitoring, liquid biopsy is a great tool because it’s minimally invasive, it’s just a blood draw and we can continue. Not all the patients have the possibility in terms of they are not all cheaters, that is something we need to know DNA, so it’s the majority of them, we can do it in some minimal proportion, we cannot do it when there are also possibilities to follow them.

Dr. Nicole Rochester: 

Excellent, and our last question from the audience comes from Laura, and she wants to know, “Are immunotherapy combinations in the metastatic setting, expanding to treat earlier stage lung cancer?”

Dr. Christian Rolfo: 

Yeah, absolutely, we have actually an FDA approval for us, one of the immunotherapeutic drugs in patients after the resection of the disease with some characteristics, but we are there and actually we are having more and more clinical trials using in earlier stages so we will say in the other stage from the earlier stage from that is the neoadjuvant and we call that when we are doing a treatment to reduce two months to be operated later on, so we have also some trials that are going there, but we have an approval already for the adjuvant setting that is after the surgery in some patients.

Dr. Nicole Rochester: 

That’s wonderful. You’ve given us a lot of good news. A lot of hopeful news, Dr. Rolfo, it is time for us to wrap up. I want to thank you again for being here for sharing your expertise. In closing, is there any takeaway that you want to leave with our audience today regarding lung cancer and advocating for themselves.

 Dr. Christian Rolfo: 

I will say that, first of all, thanks for the opportunity and it was a pleasure to discuss with you and I’d write to the population and say, Try to ask for your rights as a patient, so ask for your rights, be proactive in terms of your disease, you are the main actor here,  we are tools of trying to help you to arrive to the destination, but the good important thing is to create a good relation with your doctor, and to create a good relation with your doctor is part of the trust from both sides, so having an open communication… Open communication with the family as well. Sometimes we are smuggling or hiding things as a patient for our families to don’t help them, and vice versa that is not helping in this process, absolutely. And if you want, if you have that asking if you’re never deserving, so this is what we are here and all the team is here to help you.

Dr. Nicole Rochester: 

Wonderful. Well, I just want to echo what Dr. Rolfo said about asking questions about being an active member of your medical team, the doctors are there to assist you, but you are ultimately the expert for your disease for your body, so I just wanna thank you again deferral for being here for sharing such important information thank you all again for tuning into this patient empowerment network program. If you’d like to watch this webinar again, there will be a replay and you will receive an email when that recording is available, and remember, following this program, you will receive a link to a survey, please fill out that survey. Let us know what was helpful so that we can serve you better in the future to learn more about lung cancer and to access tools to help you get the best care no matter where you live. Visit powerfulpatients.org/lung cancer. I’m Nicole Rochester, thank you so much for joining us. 

How Will I Know if My AML Treatment is Working?

How Will I Know if My AML Treatment is Working? from Patient Empowerment Network on Vimeo.

During acute myeloid leukemia (AML) treatment, specific tests help to gauge a patient’s treatment response. Dr. Pinkal Desai details how diagnostic tests are used in monitoring the efficacy of an AML therapy

Dr. Pinkal Desai is Assistant Professor of Medicine at Weill Cornell Medical College and a hematologist specializing in acute myeloid leukemia (AML) at Weill Cornell Medicine. Learn more about Dr. Desai, here.

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What Is the Patient’s Role in Making AML Treatment Decisions?

What Is the Patient’s Role in Making AML Treatment Decisions?

Transcript:

Katherine:                  

Once a patient has started treatment, how do you know if it’s working? How do you gauge that?

Dr. Desai:                   

When a patient begins treatment, whatever their regimen is, for the most part, it takes about a month to get into remission. So, initially, with any treatment we would use, the blood counts will actually go down. Everything is down, down, down. That’s important, and it’s good, actually, because if we can’t wipe out these cells, then we’re not going to. The patient’s not going to go into remission. It’s good that these blood counts drop and they keep like that for a month.

After a month, generally, is the first look on an average to see where it is, and that kind of depends on the regimen. For intensive chemotherapy, we take a look in the middle, like Day 14, to see did we wipe out all the leukemia? And can we modify treatment so that whatever might be left behind will clean out? For lower intensity treatments, it’s about a month. So, that’s the first sort of real look at whether a patient is in remission.

And again, when I say, remission is a morphologic criteria that we see the blast count are less than 5 percent, and the cells are – the normal cells are back to what is considered within normal limits or normal for that person’s age. And the idea, at that time, is to not only just confirm remission, but like I was saying, how good is the remission.

So, that’s where MRD testing comes into play. You want to see what you want to find, even if it’s by small numbers, what is the percentage of leukemia that’s left behind. 0.01 percent, 0.001 percent. This is important.

The goal is to ultimately get that down to zero, and that’s how we use it during induction, even when they’re going through consolidation, we’re episodically monitoring with bone marrow or blood testing for some of these molecular mutations that is there continued response from where we started off? And once the treatment is done, we are still, we’re seeing these patients on a regular basis, sometimes doing bone marrow biopsies at regular intervals, to again make sure that there is continued response. And can we see something different, or is there an emerging population of cells that are worrisome, and how do we modify our treatments to try to kill these cells?

Measuring My Myeloma With MRD Testing: What Is My Disease State?

Minimal residual disease (MRD) testing is a big topic of interest for many myeloma patients and care partners. What exactly is the role of MRD testing in myeloma, and is it worthwhile?

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Watch as Cherie Rineker, a myeloma patient, Dr. Elisabet Manasanch, an oncologist at MD Anderson Cancer Center and Tiffany Richards, an advanced practice nurse, discuss how myeloma is being measured to accurately define myeloma disease states.


Transcript:

Andrew Schorr:
Hello, and greetings from Southern California. I’m Andrew Schorr with Patient Power. Welcome to this Patient Empowerment network program. This should be very helpful over the next 90 minutes for all of you living with multiple myeloma. And some people, thank God, now have been living a long time. And we’re going to be discussing measuring my myeloma with MRD testing, what is my disease state. So, testing has come a long way, and we’re going to hear the latest.

Okay. Are you ready to go? All right. Now, let’s go to Houston, Texas. We have a lot of people to meet. And one of them is a physician who is a specialist in multiple myeloma. She is at the MD Anderson Cancer Center in Houston. And that’s Dr. Elisabet Manasanch. So, Dr. Manasanch, thank you so much for being with us. She’s going to pop herself on there. And thank you so much for being with us. And we’re going to learn a lot more about myeloma testing, as we go. Also, I want to have someone else join us from MD Anderson. She’s been on our programs before. She’s a nurse practitioner specializing in multiple myeloma. And that is Tiffany Richards. Tiffany, welcome to our program. Hi, Tiffany.

Tiffany Richards:
Hi.

Andrew Schorr:
Okay. And then, of course, on every program, we always have a patient. And some of you in the myeloma community have been following Cherie Rineker from Houston, who has been living with myeloma since 2012. Not too long ago, nine months ago, had CAR T-cell therapy. But she’s been through so many treatments, and she’s in Houston as well. Cherie, welcome to our program. Cherie is going to pop herself—hi, Cherie, welcome back.

Cherie Rineker:
Hi, Andrew. It’s great being with you again.

Andrew Schorr:
Okay. So, let’s hear a little bit of Cherie’s story because, for any patient going through, you want to know how are you doing. And then, we’re going to learn from the doctor and from Tiffany more about MRD testing or testing in general. And then, we’ll take your questions, of course. So, first, Cherie, to start with, you were diagnosed back in 2012. And I think you were traveling at the time, is that right?

Cherie Rineker:
No. I was actually going to school to become a natural esthetician before getting very sick.

Andrew Schorr:
In your professional background, I know you’ve been a triathlete. You’ve been a very active woman.

Cherie Rineker:
Yes.

Andrew Schorr:
And you’ve done a lot of different things. You’ve been a massage therapist but particularly active. So, it started with pain in your arm and your side, right?

Cherie Rineker:
Pain in my side, pain in my ribs and my sternum, in my back. I was a massage therapist, so I kept self-massaging myself
with tennis balls that I would lay on trying to find the right spot. And it just would go to different places. It would never ease up. It was just slowly getting worse and worse.

Andrew Schorr:
And this went on for like six months, you were going through all sorts of problems and fatigue.

Cherie Rineker:
Right, right. Yeah. Slowly, the fatigue was getting worse and worse, to the point that my daughter was 6, at the time, and I would still pick her up, and I couldn’t do that anymore. And I had a hard time climbing up the stairs to my apartment. I ended up having low grade fevers and a lung infection that just didn’t want to go away. And I was being tested for all kinds of things. Everything came up negative. This little word, cancer, started creeping in my mind. And that’s what it ended up being.

Andrew Schorr:
And you have lesions on your bones, right?

Cherie Rineker:
They were all over my rib cage, all over my spine and my scalp, on my pelvis, yes.

Andrew Schorr:
How old were you, at the time of diagnosis, Cherie?

Cherie Rineker:
I was 44 years old. But I really believe that I had some form of myeloma for years, because I remember at 40 feeling very fragile, in my bones. And I asked my gynecologist, if I could get a bone density test. And he asked me if I was still having regular periods. I said yes, and he said you’re fine, don’t worry about it. And I think that maybe they could have found something, at that time, already.

Andrew Schorr:
I have a question for Tiffany just while we’re talking about diagnosis. So, Tiffany, she was a pretty young woman. Often, we think of people older with myeloma. But really, there is an age range, isn’t there?

Tiffany Richards:
There is. Certainly, the median age is about 69 years of age. But we do see patients who are younger being diagnosed with myeloma.

Andrew Schorr:
Okay. So, Cherie, you had your diagnosis. It’s a shocker. So, since 2012, you’ve been through a whole range of treatments.

Cherie Rineker:
Yeah. They started out they were going to do surgery on my spine. I had plasmacytomas on T3 and T4, one at one end to the spinal canal, so they were worried I was going to be paralyzed. The surgery was too tricky, so they chose for radiation. And after that, I moved from Tempe, Arizona to Houston, Texas to be closer to MD Anderson and went through nine months of induction chemo, which we changed up I think three or four times. And the side effects got worse and worse. So, we went ahead with bone marrow stem cell, my first one, in August 2013, even though I still had 80 percent of my lung and my bone marrow. And four months later, I chose for a second stem cell transplant, which only brought my numbers down to 20 percent. And then, I’ve been on continuous chemo through December of 2017, when I told Dr. Lasky I am done with chemo. It was destroying my immune system. And I was just very sick. And that’s when I started searching for a CAR-T trial.

Andrew Schorr:
Oh, man. So, you’ve been through it. There are some people who have done pretty well with transplant. Some people even have had oral therapies or infused therapies. But for you, you kept running through them.

Cherie Rineker:
Yes. And I found out later I had translocation (11;14), which is not supposed to be very aggressive myeloma. But Dr. Lasky said mine was just very stubborn. And it just didn’t do good with medicine. I would have short responses, and then, I would relapse again. And that’s how I went through the 13 different regimens.

Andrew Schorr:
And so, you had testing many different times. But the news often came back not so good.

Cherie Rineker:
Yeah. Some months, it would go better than others. And I would have a graph, in my bathroom sink, just for positive affirmation. And seeing that go down to zero, my first one, I think based on that analogy, I was supposed to be in complete remission August of 2013, which, obviously, didn’t happen. And it was just so devastating every time to see the numbers go down for a bit and then, creep back up again. And going up, Dr. Lasky often said that sometimes happens. But after so many relapses, I knew, as soon as those numbers went in the wrong direction that meant I had become refractory, and I had relapsed.

Andrew Schorr:
All right. So, just for our audience, CAR T-cell therapy that some people have heard about for this blood related cancer and for some others now, too, remains experimental, in some areas. And some lymphoma is approved, but not yet in myeloma. But you entered a trial. And, so far, over nine months now, it’s worked out, right?

Cherie Rineker:
Yes. I got my CAR T-cells back on March 12. It’s my fourth birthday now, after my birth and two stem cell transplants. And I went through a serious cytokine release storm for about a week and then, came out and started feeling better than I had in years real quick. And about three weeks later, I had my first complete remission, negative, no Bence Jones in my urine, no kappa light chains, ratio good. And then, the first bone marrow biopsy showed complete negative. They couldn’t find any myeloma.

Andrew Schorr:
And you’re going to go back for another check up soon where we hope that that still goes that way. And I should just mention, some people have seen some things we’ve posted along the way, and Cherie has, too, where I was thrilled when Cherie sent me a picture. And having been really almost at death’s door, she was out gardening, right, Cherie?

Cherie Rineker:
Yes. I do everything now. I’m back to teaching yoga and meditation. I’m doing reflexology again. I’m going to the gym, for the last month, trying to get strength in my body and my bones and my muscles. I have weened myself off all opioids. So, my medicine cabinet that was just bursting at the seams before, now, just has three little things that Valtrex, we, I guess, have to be on indefinitely and a couple of other little things. But, yeah, I feel healthier than I did probably one or two years prior to my diagnosis. So, it’s really incredible.

Andrew Schorr:
This is maybe the new age of myeloma care, with a much broader range of treatments than we’ve ever had before. And for someone like Cherie where so many other treatments that have worked for some of you who are watching were not working for her. And Doctor, I’m sure, when you hear this story, that makes you feel great that medical science has advanced, in this way.

Dr. Manasanch:
Yes. It’s great that we can use our own cells to treat diseases, including cancer. I do think that, of course, these therapies are some of the major advances that we’ve had over the last five years. In fact, when the CAR-T cells were starting, I was a fellow at the National Institutes of Health. And the first patient that got one of those infusions was a patient with, actually, leukemia. And I was on-call that night, and I was called because the patient was getting a cytogram release, so I had to send this patient to the ICU. And the patient, subsequently, did all right, but this was many years before this was going to be done in myeloma.

And then, I remember very well, when I left NIH to come here, that was in 2014, one of the days I was leaving, I kind of ran into Dr. Korkendorfer who is really the person, the scientist, that has developed this in myeloma with targeting the BCMA antigen. So, he really should have a lot of credit for this. He’s the one that really started the identification of this target that now is used in many other therapies, as well in clinical trials, not just for CAR T-cells. And he kind of was waving to me and saying, “You know, I’m going to be starting this BCMA CAR T-cell study here. So, send me some patients.” So, this was back in 2014, of course. This therapy seemed to work very well. Unfortunately, most patients still do relapse from these therapies.

And so, this just means to us that we have to keep fighting to improve these therapies. So, these are still first generation of these therapies. I think that we can improve on them. And I think there’s a lot of research going on on that. Still there are some patients, like Cherie was saying, that are years out and doing well. So, I know that is not like this or everybody. But the hope is still there that we can improve on these therapies.

Andrew Schorr:
Okay. So, that brings us to testing. So, Tiffany, you’ve been working in myeloma for a number of years. You’ve done a lot of programs. The testing keeps getting better, right? But patients are saying to you, “How am I doing, how am I doing?” Like Cherie had the picture on the wall of the bathroom charting herself. Tell us about how testing is changing and this whole term of minimal residual disease. What does that mean?

Tiffany Richards:
Yeah, it’s a good question. So, when I started working here at Anderson 14 years ago, the light chains had recently been introduced. And we were starting to incorporate them into our response assessments. But, predominantly, we were looking at SPEPs and UPEPs. But, certainly, the light chains would give us an early indicator, if a patient was starting to relapse.

And then, over time, the response criteria have improved to now that we have minimal residual disease. And how I explain it to patients, I’m sure you’ve seen the slide with the iceberg. And patients, I think, relate to that. And I explained it to them that we pushed the iceberg far down below the level of detection that, with the most testing that we have, we can’t detect the iceberg anymore.

Andrew Schorr:
Okay. But that detection of cancer cells has become super sensitive now, right?

Tiffany Richards:
Yes.

Andrew Schorr:
So, okay, Dr. Manasanch, help us understand how are we assessing MRD? So, if you are working with a Pathology Department or whoever, what tests are they doing to determine whether a patient has been treated successfully, basically?

Dr. Manasanch:
So, we’re very fortunate here at MD Anderson because we have a fantastic flow cytometry lab. And so, we have minimal residual disease testing by flow cytometry. And that’s just sending aspirate of bone marrow, so just the blood and the aspirate, when you get a bone marrow biopsy done, and sending it for analysis through a special machine that really can look very carefully at the markers around the surface of the myeloma cells. And by looking at these markers, we can determine whether the plasma cells are normal or abnormal. And we can determine how many, in that specimen, are plasma cells and then, how many are normal and how many are not normal.

And so, if we do find any that are not normal, then, that’s what we call minimal residual disease in a patient that has been treated. So, if you have multiple myeloma, and you have been treated for multiple myeloma, it is very common to do not just the blood studies and the 24 hour urine but also to do a bone marrow biopsy. And when you do the bone marrow biopsy, usually, that’s when you take a sample for analysis. Now, that’s what we do here at MD Anderson. Basically, we can detect one cell in hundred thousand, which is the sensitivity people are always talking about 10 to minus 4, 10 to minus 5, 10 to minus 6. So, ours here, with our flow cytometry testing, is 10 to minus 5, which is quite good. And it’s probably almost the best that you can get with flow cytometry, in the bone marrow. And so, we get the result within a few days. And so, we’re very lucky with that.

Now, there is also another technique. There’s a company called Adaptive Biotechnologies. And they have a test that is FDA approved. It’s called clonoSEQ. And they have different versions. And the most recent one, actually, is quite potent. And they can detect cells one in a million. So, I’m not sure, Cherie, if I may ask you, in the test that you had done, did you have the clonoSEQ test done, with flow cytometry?

Cherie Rineker:
I just emailed my oncologist, the trial oncologist, about that. And he said that I was MRD negative, with the clonoSEQ
was 10 to the negative 6.

Andrew Schorr:
Yeah. Because it’s very difficult to get the 10 to minus 6. So, the level of sensitivity is, basically, how many cells can you detect, in a sample of millions of cells, how many can you detect that are abnormal with myeloma. And so, with flow cytometry, it’s very difficult to get to one in a million. So, that’s why I suspected that’s probably done with the clonoSEQ assay. So, that test, basically, is available. The doctor has to send a sample to that company, Adaptive. And then, what I’m not very clear on is how the billing is done. Now, for here at MD Anderson because we already have an assay that is set up, it really doesn’t cost extra to patients to do. We really do it through flow cytometry. And so, that’s really what we’re doing at MD Anderson right now is flow cytometry minimal residual disease. It works pretty well. We know, from many studies, that it is predictive of how long a remission will last, in most patients.

However, each patient is so different that this is something that, whether, in your particular case, you need minimal residual disease or not is something that really has to be addressed with every patient because every patient is a little bit different. And one of major limitations of minimal residual disease is that it comes from the bone marrow. And the bone marrow is a blind biopsy, right. And so, people can have other things in other places, and we don’t see them. Now, it seems that, for most patients, it still works pretty well. But if you have a collection of plasma cells somewhere else that is not in that specific location where we do the bone marrow, that’s not going to show up. And so, that’s one of the limitations of this. And what we try to do with that is you can combine some imaging with the bone marrow test. And that even has a better prediction probably. So, you can do like a whole body MRI or a whole body PET CT. And then, you can look to see are there any lesions, anything that we’re not looking at the bone marrow. But I’m definitely having minimal residual disease negative but one to one million, which is a very good sensitivity,
after CAR T-cell therapy is excellent. It’s fantastic.

Andrew Schorr:
Oh, good. So, you got a second opinion here, Cherie.

Cherie Rineker:
And I will say I had the PET scan done as well. So, my only concern is because I relapsed so many times and so fast, how durable is this one? Will this one pop back, too? So, there’s some fear attached still.

Dr. Manasanch:
But that’s so difficult to tell because every patient is so different. Every patient is so different. And this is where it’s very easy to take a study and say 50% of these patients did this, 50% did this. But when you have that patient in front of you, it’s so hard to predict the individual rates because you mentioned, for example, I your case, all you had was this translocation (11;14), which really doesn’t signal this that this is going to happen. But it happened. And so, it’s so hard, when patients say how long am I going to live. I don’t think that we can tell. We can say, based on average, for your case, maybe this is what could happen. But really, no one knows.

So, each case is very, very individual. It’s very different. You really have to look at all of the things carefully. So, it has to be very careful analysis of each case. And so, this is why we run into surprises. But, overall, it is true that, if you have—no matter what type of myeloma you have, if you have a complete remission with minimal residual disease negativity that seems to pretend a good prognosis, in terms of the time that you stay in remission. And so, that’s important. And that usually translates into people living longer, the more you stay in remission. That’s usually how it goes. But, again, that’s a generalization. And every patient is very different. So, it’s just hard to do case by case.

Andrew Schorr:
And I want to ask Tiffany, so, Tiffany, you have patients come to you for follow-up care. And tests have been ordered along the way. And you’re going over the results with them. So, if it were me, and I had this, in my condition, chronic lymphocytic leukemia, where Dr. Wierda was also there at MD Anderson said, “You know, you’re not MRD negative.” And I was kind of crestfallen. And I said, “What does that mean?” He said, “You’re going to need treatment again sometime,” kind of like what the doctor was just saying, “but we don’t know when.” And for me, it was many years, actually, for that particular condition. But tell us how you described that because I’m sure you’ve seen people disappointed or feeling pretty good. So, how do you manage that, with your patients, Tiffany?

Tiffany Richards:
Yeah. I usually try to set expectations, right from the beginning, when a patient first comes in because all patients want to have a CR. And they all want to have the deepest remission possible. That being said, I tell them upfront that the majority of patients may not get there. But that I have patients who have never achieved a complete remission. And they’re living 20 years later. So, I always tell patients that, at the end of the day, we have statistics. And we use those to formulate our treatment plans. But they’re their own unique case. And, if you don’t get to that MRDnegative status that it’s not the end of the world, that it doesn’t mean that all hope is lost and that this is the worst thing on earth. So, I try to set that expectation right from the beginning, so that, if they don’t get it, they’re somewhat prepared for that, and that they don’t leave feeling super, super disappointed.

Andrew Schorr:
I want to remind our audience, if you have a question, and some people, certainly, have sent them in, just send it in to
myeloma@patientpower.info. Now, Doctor, let me ask you this. So, here’s the thing. You’ve got all of these variables. So, it sounds like the testing is one indication. But what are the other things you’re looking at? It seems almost like a constellation for you, as a practitioner, to know how is somebody doing. Or even, if you’ve had a certain treatment, how is that treatment going. So, tell us what else you look at. So, the MRD testing to the 10 to the whatever, 5 or 6, as you can, what else? How do you assess how somebody is doing?

Dr. Manasanch:
Well, so, the first things that we do is we have what we call our myeloma labs. And the myeloma labs include something called electrophoresis. That’s a test that looks at each patient’s individual paraproteins. Those are the proteins that the myeloma makes. So, most myelomas, about 80 percent to 85 percent make what we call—they make an immunoglobulin. And those immunoglobulins, they actually have two parts. They have a heavy chain and a light chain.

That’s how immunoglobulins are structured. And those immunoglobulins usually fight infections. But the immunoglobulin that the myeloma cells make does not fight any infection. In fact, I’m just going to go in there and say that we have some exciting research here where we’re going to be looking at whether these paraproteins target in myeloma. So, we don’t know what they target. In a healthy patient, an immunoglobulin is supposed to target an infection or something that is foreign to us. And, usually, it’s viruses, bacteria, and so on.

But in myeloma patients, we don’t know. And we’re trying to look into that to see what is going to happen with the etiology of myeloma. Now, that’s what we look at in the blood, so those immunoglobins, those paraproteins. About 10% or 15 percent of patients, they don’t have the heavy chain. So, they have only one part or two parts of the structure of immunoglobulin. Instead of having the heavy chain and the light chain, in the immunoglobulin, they just have the light chain.

So, when I say this, it may sound a little complicated, but it’s really very easy. Most myeloma patients, they have an immunoglobulin G. So, we look to see how much of the immunoglobulin G is in the blood. Some patients will have immunoglobulin A, some will have immunoglobulin M. Maybe one percent of patients will have immunoglobulin E or an immunoglobulin D as in David. Those are very rare, but we see them. So, that’s usually most patients, myeloma express some of those. So, that’s a nice way you can correlate how much tumor you have, how much myeloma you have, by how much of this protein is in the blood.

Usually, most of the time, you can correlate that pretty well. So, the higher the level is in the bone marrow, the higher it is also in the blood. And so, usually, with a simple blood test, you can already know a lot about the patient’s myeloma, if the levels are very high or not. So, the first thing we look at, again, is this electrophoresis.

And that tells us how much of those immunoglobulin are in the blood. And then, we have, also, the light chains, which are kappa and lambda. So, we look at those. Those are the second part of the immunoglobulin. And, again, about 15 percent of the patients, they don’t have the heavy chain. They don’t have the immunoglobulin G or D or M. They just have the light chain, kappa or lambda. So, patients that have the whole protein, the whole paraprotein, the whole immunoglobulin, both the heavy part and the light chain part, we look at that through electrophoresis. And that’s very useful. And that’s how we determine the response.

So, you have the patient that has an immunoglobulin G kappa myeloma, that’s what the myeloma is making. And they start with a number of four. So, even if that number goes from 4 to 2, that’s a partial response. If it goes from 2 to 0.4, that’s a very good partial response.

And if it goes to 0 that could be a complete remission. So, really, most of what you need to measure like partial response, very good partial response, is really just the paraprotein. If you have a light chain myeloma, then, you have to look at the light chains in the blood. So, you don’t look so much at this paraprotein and the electrophoresis, but you look at the light chains. So, basically, you need, for someone who has the regular myeloma like most people have that has both heavy and light chain, you just look at the electrophoresis. And that can tell you a lot already. And that’s just one test.

Then, if you want to know about complete remission, once you reach that zero, then, you have to look at something called immunofixation that tells you the type of paraprotein. You have to look at the light chains. Also, you have to look at the variations in the light chains in the blood. And you have to look also at the urine. So, usually, that’s what we do with each patient.

So, there’s a lot of tests involved in this. So, the urine, the best test to measure the urine, in myeloma, is still a 24-hour urine that measures how much of the Bence Jones protein, which is the myeloma protein in the urine, varies. And that can be done quite easily, although it’s a little bit cumbersome for patients. And you look at that. So, only once you reach your complete remission, once the numbers in the blood are negative, the numbers in the urine are negative, then, usually, that’s when we say, okay, we’re going to do a bone marrow biopsy.

And then, if the bone marrow biopsy is negative, the bone marrow is normal, then you can do your MRD testing, your minimal residual disease testing. And that’s how the levels of remission. However, it gets a little bit tricky because you can have a patient that has still some paraprotein in the blood. So, the blood markers are positive. The urine markers are positive. And then, you do your bone marrow, and you do your minimal residual disease testing, and that is still showing a little bit of the—sorry, that is, basically, negative.

So, you can have an MRD-negative test. And you can have patients having some paraprotein in their blood. Okay. The main explanation for this is because the paraproteins, the IgG kappa mainly, takes a very long time to disappear from the blood. So, you may actually be looking at the bone marrow, and you don’t see any myeloma in the bone marrow, and that’s actually a good thing. What it likely means, for most patients, is that, with time, what they’re seeing in the blood will go away. So, it does seem that the IgG kappa tends to linger in the blood.

So, if you have patients here that have IgG kappa, and they have a minimal residual disease testing in the bone marrow, and that is not normal, and they still have a little bit of their IgG kappa in the blood, then, it is likely that this will actually go away with time.

Whereas, if the MRD testing is positive, it is a little bit more difficult. So, it can give you chances. But, basically, there are a lot of tests that we use.

Andrew Schorr:
Wow. So, I want to say, first of all, thank you for that because ladies and gentlemen watching are living with myeloma. Now, you hear how complicated this is to really understand, maybe not for Dr. Manasanch, but for some, particularly community oncologists around the country, around the world, to really help you get a clear picture of what’s going on with you. And this whole thing about lingering of some of these paraproteins where you’ve had an MRD negative test, I’d say, oh, I have an MRD-negative test. And then, if this other one came up, I’d say, oh, my God, could you explain the linger. And it’s maybe not such a big deal, right?

Dr. Manasanch:
It doesn’t have to be a big deal. And, usually, it still is a good thing, if you have still a little bit of protein in the blood and they myeloma.

And then, the bone marrow is normal, and the flow MRD or the clonoSEQ is negative that usually, probably, means that it’s just taking you a little bit longer to clear that protein from the blood.

Andrew Schorr:
Wow. So, Tiffany, the doctor rattled off a whole bunch of testing and light chain, heavy, light. If somebody is diagnosed with myeloma, and I’m sure this—Cherie, you’ve sort of gone to school learning this, over the years, but it is overwhelming to try to understand this. Obviously, you have to have a healthcare team you trust. How do you help people through this? Because they want to know how am I doing.

Tiffany Richards:
Right. That’s a good question. I think you’re looking at your patient in front of you. So, you’re going to tell them what they need to know, what our goal for them is. So, if they don’t have light chain—if they have a regular myeloma, you’re going to talk about their M protein and what we want to see their M protein go to.

And so, you’re not having to like go through everything all at the same time. Usually, the physician I work with will explain the iceberg discussion to the patient, at their initial visit. But, obviously, there’s a lot of information that’s given to patients, at that point in time. And so, you’re really just trying to take it—I try and take one step at a time, with patients because I find that they get very overwhelmed with information overload. And so, trying to break down that information, I think, is useful for patients, rather than giving it to them all at one time and just reiterating to them, at each visit.

Andrew Schorr:
Good, thanks. So, Dr. Manasanch, what do you tell patients? So, again, you’ve said, well, we’re going to do this test, or we’re looking at these proteins or light chains. How do you help people work with you to have confidence that maybe things are working?

Dr. Manasanch:
Well, I know it seems complicated, but it’s really very easy. The way we have our results, at MD Anderson, is it comes through the paper sheet that has all of the results there very clearly. And you can really point out, okay, this is your result. This is the number. This is your starting point. So, I just say this is your starting point. This is your number. Now, we want this number to go to normal. For the M protein or paraprotein, the normal number is 0. So, we would like the number to go to 0. That’s what we would like. Now, not everybody goes there. What does it mean? Well, for some patients, even if they don’t get there, it doesn’t matter.

They still do really well. For some patients, they don’t. Do I know, when I look at the patient? I cannot know. So, then, I don’t think that it’s very important because I pay a lot of attention to the things that I know that will impact.

So, whereas it is true that, for most patients, it is better for these M protein or these paraprotein to go to 0, there are some patients, as Tiffany said, that it never goes to 0, and they’re still doing great. And they don’t need anymore treatment. Some of them, they have the same number, zero point something, for years without treatment. So, it’s very difficult to say. So, I think it’s very important. The way I explain it is that we want this number to go to 0 if possible. If it doesn’t go to 0, then, we’ll talk about what to do, at that time, and whether we need to do something for your case or not because everybody is different.

And the people that have light chain disease, which is measured through the light chain test, then, I just go and say, okay, this is the light chain. This is what you have. We want this number to go to normal. Normal is around 10 to 20, something like that. We want this number, which is the ratio, to go to around 1, 1, 2, 3, something like that. And that’s our goal. That’s what we’re going to try to accomplish.

And then, when this number—I don’t go and explain all of this and MRD in the first visit because it’s too much. It’s just a lot. And patients with myeloma, they become your friends because the come to see you really every month. You see them all of the time. So, you have so many opportunities to talk about those things in follow ups that I just say the goal is to get you better, get those numbers reduced. And then, we’ll go and see from there. And then, in subsequent visits, then, we discuss, okay, well, guess what. This number is close to 0. Or we’ve done already a few months of treatment.

How about we do a bone marrow biopsy, and we look at minimal residual disease. And then, I discuss that. So, that’s usually how I do it. We break it down a little bit. And I don’t go into so much detail. But the patients always have all of their results. I usually give all of the results to my patients, so they can process them. They can look at them. They can become familiarized with them. I think it’s very important for patients to know what they’re looking at, what results they need to be aware of. And so, I certainly point to that probably at every single visit for every patient.

Andrew Schorr:
Okay. Cherie, what were some of the test results that you were following closely for you to feel how you were doing?

Cherie Rineker:
So, for me, I never had an M spike. And so, I guess that means I didn’t have the heavy light chain. Did I get that
correct?

Dr. Manasanch:
Yes, that is correct.

Cherie Rineker:
Okay. So, I never had an M spike. I believe my kappa light chain started out in the tens of thousands like 17,000, and my Bence Jones was around 8,000. And so, I was very afraid of chemo. I did my first month of lenalidomie (Revlimid), dexamethasone (Decadron) and bortezomib (Velcade). And my kappa light chain, actually, went up, after the first month. But we had a little accident at MD Anderson.

I had not put the lid good on the 24-hour urine. And my husband picked it up, and half of it ended up in his shoe, which got him very upset. But when we went to Dr. Lasky the next time, Dr. Lasky kind of gave me a high five on the Bence Jones. He said, “I don’t understand because your kappa light chain had jumped like 1,000.” He said, “But your Bence Jones went in half.” And I was very out of it. I was on a lot of medicine, at that time. And as an afterthought, I said, “Well, we did lose half the bottle of urine.” I told him the story. And I remember the look on his face went from, okay, this is a good thing to concern.

And looking back that little accident actually probably saved my life because being a holistic practitioner and being so afraid of chemo, probably had I known that both of the numbers had gone up, I probably would have said I’m not doing this anymore.

See, I’m right, and chemo is not good, and we’re going to stop it. So, the next month, the numbers slowly started coming down. They didn’t do a bone marrow biopsy for me. Well, they did one, and it was inconclusive. And then, they did another one, nine months later, before my stem cell transplant, which then showed 80 percent in the bone marrow. And I had asked Dr. Lasky what is a good way to go into the stem cell transplant. And he said, “We like patients to be between 0 and 5 percent.” So, needless to say, when I heard 80, I was pretty…

Andrew Schorr:
…you had quite a journey. So, we’re going to take some questions, in just a minute. Caroline has already sent one. Caroline, stand by and send them to myeloma@patientpower.info. So, Tiffany, some of the testing is to see what subtype of myeloma you have. Dr. Manasanch was talking about that.

Do you have this type of myeloma or that type of myeloma. So, some of the testing is related to that. So, is that sort of
step one is to see what’s your myeloma and how do we measure that? Is that where you sort of start?

Tiffany Richards:
Well, when you’re looking at an M protein, you do have to know what type of myeloma that they have. And a lot of patients, particularly patients who are active on blogs and support groups and stuff, always want to know what type of myeloma do I have. And so, the immunofixation will tell us what type of protein is being produced. So, whether it’s an IgA kappa or an IgG kappa, or in the case of a urine protein electrophoresis, it will tell us if it’s a kappa or a lambda. And then, we look at the M protein as well.

And I wouldn’t say there’s a Step 1 that we look at and then a step two because I think, when you’ve been doing this for so long, it’s more fluid than that. But that’s what patients want to know is what type of myeloma do I have.

Andrew Schorr:
Okay. And then, just to be clear about the MRD testing, which becomes more and more sensitive, is that really kind of later in the process to do the MRD test? Where does it fit in?

Tiffany Richards:
Yeah. So, usually, the MRD testing is not going to happen, until the patient is in a good remission. And so, generally, if the patient has achieved a complete remission, or if they have a small amount of residual protein, then, you may consider doing it. It really depends on the patient situation and where they are, in their journey.

Andrew Schorr:
Okay. What about do it more than once? Do you get a remission, but then, later somebody comes out of remission? And later, would you do it again?

Tiffany Richards:
Generally, for a patient who is not on a clinical trial, at this point in time, we may recheck it. But for the physician I work with, we, generally, won’t recheck it because, at this point in time, it’s not like we would change—so, if a patient is on maintenance, lenalidomide, for example, and they achieved an MRD negative, and now, they’re MRD positive, but everything else is still looking okay, their numbers aren’t changing, we wouldn’t necessarily change treatment, at that point.

And so, it’s really going to be patient dependent. Sometimes, you’ll get them once a year, but, again, we don’t necessarily change treatment because a patient went from an MRD negative status to an MRD positive status.

Andrew Schorr:
Okay. Doctor, do you have a comment about that, about how often do do MRD or when?

Dr. Manasanch:
Right now, if you are on a clinical trial, the clinical trial, basically, tells you when you’re going to test for this. If you’re not on a clinical trial, I’ll tell you when I do it. And I think also, a lot of physicians do it at MD Anderson, which is usually before our stem cell collection.

So, newly diagnosed patients, they come in. Okay, yes, we confirm this is myeloma. This needs to be treated. They get treated. The response rate for the treatment of multiple myeloma right now, with the therapist that we use at MD Anderson, the response rate is 100 percent. So, basically, everyone, maybe 1 patient in 300 doesn’t respond. So, we can say response rate is 100 percent. So, all of them are going to respond or almost all of them. And then, we get ready. Most of the times, most patients actually, in our center, about 80% of newly diagnosed patients choose to do an upfront autologous stem cell transplant, which means that they need their cells collected.

And they proceed to get high-dose melphalan (Alkeran), which is the medication that is given with that transplant process. And so, we check the bone marrow to make sure that, actually, we’re not going to pick up a lot of bad cells with the stem cells.

We check the bone marrow because we also want to have a good response, whatever response you have, usually, before a transplant. The marrow transplant outcome, again, for most patients, but generalizations do not apply so well to individual patients and their cases. So, every patient is different. But, usually, we check the bone marrow biopsy, before we do the stem cell collection. And then, the bone marrow biopsy, after treatment, usually includes a minimal residual disease testing. So, that’s definitely something that we kind of consent to do at MD Anderson.

After that, it really is physician dependent. And it’s also patient dependent. So, all of us have a patient who wants to have a bone marrow biopsy every year and have minimal residual disease testing and seeing is it coming out of remission or not. Right now, there is no evidence coming from a clinical trial that that’s going to add any benefits.

So, for example, doing a bone marrow biopsy once a year to see the minimal residual disease, whether it’s positive or negative. We don’t have information on that. However, from our experience, I believe that we will be doing this in the future. So, patients will get minimal residual disease testing in the future. And that will determine what we do with treatment. Why? What Tiffany said. First of all, it’s common sense. It’s a little bit of common sense. But all of the studies, all of the evidence that we start having from clinical trials will be showing is that the earlier you know and the earlier you do, the patient seems to have better outcomes.

And that translates to smoldering myeloma, hopefully. So, now, I keep hearing more and more stronger voices about
maybe treatment of that. So, that’s a big area also in myeloma. Why?

Because, as Tiffany said, they use the paraproteins, the electrophoresis, the M proteins. And then, they have the light chains. And the chains are a little bit more sensitive. So, then, now, we don’t wait. So, the patient has a paraprotein, an M protein, of 0.0, and then, we don’t wait for that paraprotein to be 1, if the light chains are high. If a patient has the light chains are going up, we treat the patient, if they’re consistently going up. We don’t want for the paraprotein to be a certain number. So, I feel like a minimal residual disease would be something similar.

I feel like patients who will have the minimal residual disease, if they’re minimal residual disease is negative, they will have the testing done. And if we see that that starts to change, maybe the frequency of the MRD is increase. So, now, instead of doing your minimal residual disease testing every year, now, because it turned from negative to positive, now, we’re going to check it again in three months.

And guess what, if, in three months, that’s also higher, then, maybe you change the treatment, or maybe you start treatment. Now, that’s in the future. That’s what we are hoping to achieve, with all of this. And I think that a lot has done in the last few years. I believe that the Food and Drug Administration, the FDA, will actually approve minimal residual disease as an end point for clinical trials. So, basically, the response how drugs are going to get approved is not going to be just, if your remission is longer or if you live longer. But if you get drug A versus drug B, in a clinical trial, what is the percentage of patients that are minimal residual disease negative. This is going to happen. And so, right now, the use of MRD, I think, has either been limited to when we do our bone marrow biopsies in patients after treatment and the significance is prognostic. So, overall, for most patients, if you’re MRD negative, it’s better than if you’re MRD positive, again, for most patients. And that’s all that we can say right now, today, is prognosis. But in the very near future, I think that we will do things like changing treatment. Maybe we’ll do things like stopping treatment. I don’t know. But we have a lot of studies that are looking at this right now. And they will report, in the next few years. So, this is where all of this is going. And right now, MRD is limited, I think, it prognosis. If you want to know your prognosis. And then, if you’re MRD negative, and you have to have it tested every year, you can. There’s nothing against it. What do we do with the information, if it turns positive?
It’s a little bit ahead of the time where we have full answers. But it depends on the patient and the physician a lot.

Andrew Schorr:
Okay. This was a very complete answer. So, questions are pouring in. So, we’re going to start getting a lot of questions. Just so I understand, so the MRD testing today is only from the bone marrow, or can it be done from the peripheral blood, too, doctor?

Dr. Manasanch:
That’s a great question. Right now, it’s only from the bone marrow.

Andrew Schorr:
Okay. But that may change.

Dr. Manasanch:
That may change. We, actually, have a study here at MD Anderson that I hope is going to be starting by the end of the year, which is going to be looking at something called the single cell assay, looking at, basically, each myeloma cell in the blood and doing very complete analysis, anomic analysis, something called proteomic analysis, looking at how the different cells are a little bit different. I think that, in the future, we probably will be able to do a blood test. We are not close to it yet. So, I don’t think, as I tell you, MRD, FDA approval for regulatory trials, I think, it will be soon. MRD testing, for the treatment decisions, soon, sooner rather than later. Maybe a test in the blood, maybe not so soon. So, maybe a few years.

Andrew Schorr:
You need a crystal ball. Okay. So, Tiffany, I think we’ve been talking about when MRD testing is typically done or when could it be done. And then, so Matt says, “What about the cost?” So, how do you guide people. Where does the cost come in, Tiffany? What are the costs of MRD testing?

Tiffany Richards:
Yeah. So, I know that Medicare will now pay for MRD testing, but that doesn’t necessarily…

Andrew Schorr:
…you said they will pay for it?

Tiffany Richards:
Yeah, for the clonoSEQ, they will pay for MRD testing, Medicare will. Whether or not other insurers, I have not heard from any of our patients that they’ve had difficulty or that they’ve had denials or that they’ve had to pay out of pocket. So, I think, by and large, insurers are reimbursing.

Andrew Schorr:
Okay. Now, some of these questions, folks, I don’t have myeloma, so I’m not as well versed as some of you, but let’s do
this. Matthew asked, “If you have M protein 0.1 or 0.2, should you get MRD testing?” And otherwise, you have negative numbers. So, Doctor, he’s wondering, with a 0.1 or 0.2, the M protein, should he have MRD testing?

Dr. Manasanch:
It depends. So, a patient that has—so, just a generalization. A patient who has very little paraprotein in the blood, assuming this I like a regular myeloma, most of the myeloma types that have both the heavy and the light chain. And then, you have 0.1 and 0.2. So, the response for these type of patients is usually what we call a very good partial response. Why? Because most myeloma patients that have this type of myeloma, the M proteins or paraproteins, they’re in the range of 3 or 4 or 5 grams, when they start. So, by the time they reach 0.1 and 0.2, that’s already more than a 90 percent decrease. And that’s what we call a valuable partial response. So, if you have a patient—if you’re a patient, and you know that your response is a very good partial response, does it make sense to test for minimal residual disease for prognosis?

It makes sense, for what I mentioned. Actually, if we look at the patients who are in very good partial response, and we look at MRD positive or negative, the patients who are negative tend to do better, in terms of how long their remission will last. So, if you have—you are in very good partial remission, and you want to know if this test if the clonoSEQ or if the flow is going to find any myeloma cells or not, if it does not find any myeloma cells, if you do not have myeloma cells that the test can find, that’s usually better than if the test finds some for patients in very good partial response.

So, what happens is do you want to test for it in partial response. Well, let’s say it’s not 0.1 or 0.2, the protein is 1.5, it can still probably predict. But, at that range, most patients be positive. So, it really starts to make sense, when you have very little in the blood, very little protein in the blood, and a very good partial response or very good partial remission range or complete remission. That’s when you can actually discern. If you test diagnosis or if you test partial remission, most patients will be positive. So, you can test, but it’s going to tell you what you already know.

It’s positive. So, then, what’s the point. So, for this patient, if it is a very good partial response, if the response is a very good partial response, it makes sense to, basically, talk to your doctor and say, okay, is this something that we need to do or not. Because it’s only prognosis, it’s really just to know. It’s not going to—it’s probably not going to change.

Andrew Schorr:
I think Matthew wants to know, and I’d want to know, too, because you have those very low numbers. I think, to get our head on straight, wouldn’t you agree, Cherie, you want to know?

Cherie Rineker:
Yeah. Just for peace of mind.

Andrew Schorr:
All right. Let’s get to some more questions. So, Valerie wrote in. She said, “If I’m declared MRD negative, is there still a need to take maintenance therapy indefinitely?” So, Doctor, do you want to take that one?

Dr. Manasanch:
So, the first thing is that my first inclination to that answer is, right now, we’re November 19, 2018. So, as of November 19, 2018, today, yes, you have to continue, even if you are MRD negative because being MRD negative, all it means is that the test cannot find the cells. But we have a problem in myeloma. We have a big problem in myeloma. And in myeloma, we really cannot seem to cure it, for most patients. Which means we cannot get rid of it. It’s still there. So, our worry, when patients come out of therapy, especially if they’re doing well with their therapy, right, it doesn’t have a lot of side effects, and they want to come off of it just to come off of it or because you’re MRD negative, the problem is, okay, what’s going to happen.

So, I actually had plenty of patients to where complete remissions, MRD negative by our flow cytometry, and I’ve taken them off therapy because they’re older patients. And this is relapse because there’s really, it’s the discussion because they’re coming, and they’re not doing well.

They get admitted. They have infections. They are not doing well. So, then, okay, well, everything looks good. Let’s give a break. And the myeloma comes back. And then, you treat it again, and it goes into another remission. And then, it comes back again. So, being minimal residual disease negative, in relapsed myeloma, you still need to treat it.

Andrew Schorr:
Okay. There’s an elephant in the room here, though. Cherie, so with this 10 to the 6, you’re negative. The most sensitive test available. You’ve had the leading edge of treatment, CAR T, and yet, you’re hearing the doctor say we don’t think we are able to cure myeloma and that it may come back. So, you’re hearing this. What are you thinking?

Cherie Rineker:
Well, I belong to a CAR T Facebook group. And, sadly, there are people who have relapsed. There are people that have passed since relapse. And I have pretty severe post-traumatic stress syndrome, from everything that I’ve gone through from the many relapses. And so, I’ve noticed the further out I get, the worse my anxiety is getting actually not being on any treatment. So, hearing this, again, I feel that, at this point, maybe I want to go on maintenance. But I think it would disqualify me for the trials. And I want to be part of helping the CAR T research. At the same time, I can’t fathom the thought of having to go through another relapse.

And for me, even though the numbers are really small in the end, the plasmacytoma 9 centimeter, which popped out of nowhere, within a month, the cancer was so aggressive. So, would you recommend, doctor, that I should pursue a maintenance regimen?

Andrew Schorr:
But you’re in the trial though to see how long it lasts though, too.

Cherie Rineker:
Yeah.

Andrew Schorr:
Well, I think I’m just going to comment on this. First of all, I think Andrew’s question, so this maintenance usually applies to newly diagnosed patients, right. But I made my case with relapse because what happens, newly diagnosed patients, usually, the therapists we have now are so good. Most of the patients do really well, right. I think that this is the main thing of the webinar is patients with myeloma do really well right now. I think this has to be that, most patients do, okay? Once the myeloma has come back, and it has come back a few times, it just takes less time to come back.

So, my experience with doing minimal residual disease testing has been that. You can have somebody who has relapsed myeloma who is MRD negative. That does not mean that they’re always going to stay like that. But that also doesn’t mean it has to com back. I’m just saying that it can be either way. But for maintenance like after transplant or maintenance after your initial treatment, when you’re doing just continuous therapy, probably the right thing to do is to continue, even if you’re negative, continue that therapy because we really don’t know.

We don’t have data. There are studies now where, if you are MRD negative, they stop the therapy. And if you’re positive, they continue. Right? And, in fact, you’re negative, some patients stop, some continue. So, basically, we’re going to see, in the next few years, if you can stop it, if you’re MRD negative, if you can stop the maintenance. But right now, there’s no evidence, specifically, for your case, after CAR T. There is no evidence, right now, that starting therapy will make it last longer. So, probably , you don’t have to do anything. But for the newly diagnosed patients who go on the maintenance, they’re negative. Basically, that’s not affecting how we treat. It’s just an information. It seems like that’s a very good prognostic factor. But whether we have to stop the maintenance, that’s up in the air. And for most patients, I would probably say don’t stop it. Continue it. until we have at least some studies saying that, okay, if you’re negative, you can safely stop it. That’s what I would do. I’m just going to play a little bit devil’s advocate.

Andrew Schorr:
I would just say that, for me, just listening, there’s an old phrase don’t mess with success. Right now, you’re living your life. You’re going to go from—when you’re in a trial, part of the thing with the trial is to understand how long can you have this. Here’s a question we got in from Darrell. And, doctor, I think you answered this, but I just want to make sure. So, he said he did have a very successful CAR T, and all markers of disease in the bone marrow were zero. PET scan analysis, no evidence of rival disease. But the M spike, after 90 days, has remained 0.1. Is it possible, and I think he said this, that the M protein just takes a little while?

Dr. Manasanch:
It’s possible. It’s possible that maybe there are some cells that are making that M protein somewhere. But, again, as
long as the cells don’t get worse, who cares? If you have an M protein of 0.1, and that’s not making you sick, and it’s
going to stay 0.1 for 10 years, that’s not going to kill you. An M protein of 0.1, that doesn’t get worse. So, the key here
is, if you stay there, that’s okay. The problem is, if it goes from 0.1 to 0.2 to 0.4 to 1.0, That’s when we get into trouble.
If, for some reason, there is the balance of your body or immune system is just letting some cells be there and make a
little bit of protein, and that’s it, that’s great.

That’s all you need, to not get into trouble, with the myeloma. So, that’s possible, of course. You can have everything negative and a little protein, and the light chain is a little bit high. That happens. But it could just be that it’s just lingering a little bit longer. It could be that there are some cells making it that are not doing much. It just has to be followed.

Andrew Schorr:
Okay. Just to be clear, Darrell asked a follow up question. After CAR T, then, why not start a maintenance treatment,
even if you’re MRD negative? So, is that what is the protocol for the CAR T? Or what are you doing at MD Anderson?

Dr. Manasanch:
Well, that’s a very good question. I think that’s probably like the next generation of studies, with CAR T. So, right now, when we design clinical trials, you have to, basically, make an end point, right? So, what’s your goal, when you do a study? What do you want to prove? What are you trying to say about this?

And they do studies with CAR-T cells really mostly have two end points. One is safety. So, make sure that you’re going to give the cells. People are not going to die from toxicity. They’re going to actually going to be able to go through with this. And then, the second one is how effective is this, so what are the responses? How long does it take after a response for the myeloma to come back? So, those are the main things. So, if you do a CAR T, and then, you put a therapy right after, it’s very difficult to isolate the effect of the cell therapy. So, you, ideally, want to do a study with cell therapy that is just a cell therapy.

Now, once we have established that this cell therapy is safe, and the CAR Ts are safe, and they are effective, then, the
next generation of studies is you can add things to it. Usually, we have to build on things. So, you have to have a basis.
So, right now, there are already studies looking at comparing CAR-T cell to standard therapy.

So, for like patients that are not just relapsed after 10 lines of therapy, patients that have relapsed a little bit sooner, maybe like second lines, first or second relapse. You can get CAR T, or you can get another therapy. And then, basically, this is something that has to be studied. There is no data, right now, that I’m aware to do any therapy after CAR T cell. So, that’s why people don’t do therapies because we have not gotten to it yet. So, that’s a good question. Somebody is probably doing a study right now doing therapy after CAR T cell. But I have not seen any results from any studies like that.

Andrew Schorr:
Tiffany, here’s a question that came in. This person, they’re anonymous, don’t know if it’s male or female. I’m 55 years
old, and I’m MRD negative after 1.5 cycles of treatment. My doctor wants to do stem cell collection but possibly not yet the transplant. Does MD Anderson ever skip the stem cell transplant and just freeze the cells, just wait?

Tiffany Richards:
Yeah. Certainly, there are some patients that we do that that, if they are MRD negative that would be a possibility. But, again, I think that’s a discussion with your physician because there’s a lot of other factors that come into play, such as what are their chromosomes, are they high risk, standard risk, their level of presentation, what the PET looks like. And so, it’s really going to be patient dependent.

Andrew Schorr:
Okay. doctor, here’s a question, and maybe you can decipher this for me because I’m not that familiar with it. Nicole writes in what is your experience with the presence of only oligoclonal bands? Can it ever be a band sign? I’m nine months out from stem cell transplant. And the M protein went from 0.06 to the bands in the last one.

Dr. Manasanch:
So, oligoclonal means that it’s normal. It’s like your normal immunoglobulin. So, that’s usually a good sign. It means usually the sign of deep remission. So, that’s a good thing. What that means is you probably have a deep remission, which is usually either very good partial remission or a complete remission. And what it means is that you’re normal, you’re actually starting to have normal plasma cells in your bone marrow that are actually making normal immunoglobulins. And so, the pathologist, when they look at your electrophoresis and your immunofixation, they’re seeing that there are normal immunoglobulins. And they just say, okay, we see some bands in this test. And these are probably just normal bands. So, that’s a good thing to have.

Andrew Schorr:
Okay. Tiffany, so, we’ve been talking a lot about CAR T. And I just want to help everybody understand what it is because it’s been very much in the discussion of myeloma for people like Cherie who needed lots of treatment. How do you explain CAR T to people?

Tiffany Richards:
It’s a good question. What I explain to them is that because a lot of patients have already had stem cells, so they’re familiar with having their stem cells collected. So, I tell them it’s similar to that, but we’re going to collect your T cells. And T cells are a type of white blood cells. And those cells will then be collected and sent to the company where they will manipulate the T cells to go after the myeloma cells. And that they will get chemotherapy prior to having their stem cells reinfused. And then, their stem cells will be reinfused. So, a lot of patients, they’re pretty familiar with it because they’ve all had stem cells.
So, they get chemo. And then, I’m going to get the stem cells. And so, that’s usually how I explained it. I try to keep it pretty simple, for them, because it’s quite a complicated process.

Andrew Schorr:
Right, okay. And so, where are we now, Cherie? You went through it. And so, for you, it was kind of the leading edge because you, I don’t want to say you failed the treatments, the treatments had failed you. And so, this was really your last hope, right?

Cherie Rineker:
Yes, it was. The last time I remember going to MD Anderson and talking to my oncologist, and he said, “Well, we can now go to four different medicines, instead of the usual three.” And he’d had a couple of patients, and it seemed successful. And I just knew my trend. And, at that point, I needed monthly platelet infusions and filgrastim (Neupogen) shots constantly. So, it was both the chemo and the cancer were destroying my body. And I had heard about CAR T. And I said I’m done with chemo. I want to really pursue the CAR T, which, sadly, at MD Anderson, they started it I think a week after I had my cells returned to me. So, it’s been a 14 -our flight or $500.00 ticket to…

Andrew Schorr:
…there’s an element, as these trials open up. So, I just want to go—first of all, we do have time for a few more questions. So, send them to myeloma@patientpower.info. And I mentioned Caroline a long time ago. Caroline, I didn’t want you to feel lost. So, let me see if I understand. She says, “How will knowing disease state or using MRD measurement technology change treatment plans?” So, Doctor, I just want to understand. So, what do you do with the information? So, somebody says what’s the prognosis, is it changing what treatment you use or when, based on the MRD results?

Dr. Manasanch:
We don’t have any evidence to change treatments. So, these are all questions that need to be answered, in the next few years. So, the question of, if you are in complete remission, MRD negative, and then, you get another test done, and you go from negative to positive, do we start treatment, if you are not on treatment? If you were on treatment, do we switch it? All of those things, and how often do we test for it. We don’t have an answer for those questions. We really don’t have a guidance for that. So, it’s really just, when we test for it here, it’s just so because the technology is available.

And we know that it’s prognostic. So, we know that patients that are negative, they seem to do better. So, it’s nice to have the information, but there’s not much that we can do with it, right now, except just make someone happy telling them this is already negative. But there’s not much that you can do with information. And that’s why Tiffany was saying, Dr. Weber, ewe don’t do it, unless—we test after treatment.

And every time after treatment, we test for it. And if it’s negative, okay, we know that’s the best level of remission that we have. But what does it mean, in terms of treatment? We don’t know that. So, a lot of centers don’t even do MRD.

Andrew Schorr:
Okay. Yeah. So, that’s my next question. So, we have people all over the world watching. So, Cherie has been a patient of MD Anderson. She also went over to Nashville. They have a big center there. These are major centers. But a lot of people are treated at not such a good place or maybe not even with a hematologist/oncologist who has a big myeloma practice. And we’re talking about very sophisticated testing. We’re talking about 10 to the 5, 10 to the 6, super sensitive testing. And you’re saying well, what would we do differently?

So, should people watching, Tiffany? If somebody said to you, I live somewhere else in Texas, but I come to MD Anderson—but should the local level, in Lubbock or someplace, should I be lobbying for MRD testing? Tiffany, what do you say? I want to get the doctor’s response, too.

Tiffany Richards:
That’s a good question. It’s also a hard question because, for me, I always go back to, if you have a test, is it going to change what you’re doing? And while MRD status is good to know, I always also go to the flipside. If a patient is told they’re MRD positive, how are they going to feel, after that result. And then, if they’re in a community practice where they’re seeing an oncologist who maybe doesn’t see a lot of myeloma, and now, you have this patient who feels totally deflated because they’re MRD positive.

They go and they look on the internet. And they see, oh, my gosh, my prognosis is worse. And so, what happens, in that scenario? And so, I feel like we shouldn’t leave patients out there who are going to be feeling deflated, without being able to pick them back up and give them hope. And if they’re not in a place where that can occur, then, maybe it’s better not to do the testing. But, again, I think the patient’s situation and having the patient have that discussion with the oncologist is important. But I certain feel like a patient should be able to also have hope, if they do come back MRD positive.

Andrew Schorr:
Doctor, what do you say? Again, you do MRD testing, at certain points, because—and you’re also doing research with your colleagues around the world trying to figure out where does it fit in, and what do you do about it. But that’s not always happening, at the community centers. And they’re not doing that research. So, just for our worldwide audience now, what do you want to say about MRD testing? And I’ll just say for me, and I think, Cherie, you agreed, I want to know, personally.

Cherie Rineker:
Yeah.

Dr. Manasanch:
Most patients, when given the option, they prefer to know. I think, for patients though, one thing that we try to have a community of oncologists and practices. And our own techs actually send their samples here, so we test them here. And it just turned out to be something that was logistically not feasible to do. So, we’ve tried to do this, so that people that cannot come here, their oncologist can send the samples. And the physicians will be happy to do it. But, in terms of our lab, the volume and all of this, it’s just not practical.

So, this is not something that we could achieve. Now, for the community oncologists, community oncologists, usually, they don’t test. They don’t do advanced flow cytometry. So, minimal residual disease testing requires advanced flow cytometry, which is like a new generation where you have some machines that can test many cells, at the same time. You need to have some software that can do that. You need to have someone who is very experienced. If you don’t have a very experienced pathologist reading this test, they’re going to result in tests that are not correct. And that could be an issue.

And so, I think that, if you don’t have the technology to do it, it’s better just not to do it. I think that, when we start changing treatment with this, I think that everyone will open up to it more. I think that it’s very good that the FDA has approved the clonoSEQ test to test for minimal residual disease because I think that’s easy, so the community oncologists can send the samples to Adaptive Biotechnologies.

And they can test us and give our result back. And now, the advantage of—so, that’s, basically, what I would say to these patients. But let me just add something to that. So, basically, if you don’t have it, don’t worry about it. If you really want to have it, and your place doesn’t offer it, you have to go somewhere else because, if where you are, they don’t have it, it’s better that they don’t do it because it’s complicated to get set up. It’s not easy. But now, if you compare flow cytometry to sequencing, so that’s DNA sequencing, DNA sequencing seems to be better.

And so, this clonoSEQ test, the advantage of this test compared to flow cytometry is that, with this test, you can look at different populations of myeloma, within the same patient. So, if you send these tests on diagnosis, they’re going to tell you, okay, 80% of the myeloma has this. And then, the rest, 15 percent, looks like this, and 5 percent looks like this.

And it’s going to tell you that. Whereas the flow cytometry doesn’t tell you that. Now, this test can be done, the sequencing, can be done on almost any patient. Flow cytometry can be done in every patient. So, some patients may not be able to do the sequencing, with the new generation of the sequencing test, the clonoSEQ. Every time, they can read more and more patients. But those are the main limitations. The main limitations of flow cytometry is it cannot inform you on the biology of the myeloma, in terms of how many different myelomas are there, sub myelomas are there in the myeloma.

So, that test cannot inform you of that. But some patients may not be able to do it. Whereas the flow, you can do it in everybody, but it’s not going to tell you about the subpopulations of myeloma. So, those are two tests that are, basically, used for right now.

Andrew Schorr:
I take away as sort of the common man here a couple of things. One is, and we’ve said this on so many of our programs. Cherie, I’m sure you agree. First of all, if you’re living with myeloma, I, personally, think you may want to check in or get a second opinion at a major center, whether it’s MD Anderson or one of the others. And I like the full work up. The other thing that’s going on is the testing continues to advance. So, if I got you right, you’re talking about one person having almost little subsets of myeloma with their own blood, right? Not just one myeloma, but different types. So, it would be super sensitive. Then, the question is what does it all mean differently now that you know. This is like crazy-making. So, it’s kind of like, first of all, have a team that you trust. And recognize, thank God, wouldn’t you say, Cherie, that myeloma patients, in your wonderful example, are on a much longer journey now than ever before You’re such an example of that. And so, this discussion, you’re kind of flowing with your myeloma. Hopefully, it doesn’t come back, but if it does, the testing is going to be more sophisticated. The treatments are going to be more tailored.

Cherie Rineker:
Yes. If I may say, too, when I was first diagnosed, I found out I had multiple myeloma, which I was told was a tradable yet incurable disease, at 44, that’s pretty devastating news. I thought, if I get cancer, you’re going to treat it aggressively. I’m going to go bald for six months or a year, and then, my life goes on. That’s what I thought about cancer. So, to have something that continues on and on is pretty tough to live with. Hopefully, getting to an older age.

And for me, the journey has been both physical healing and emotional healing. And physically, I’ve gotten better and better through the years, now, thankfully, after CAR T especially. But, emotionally, too, that is a lifelong commitment and exercise of trying to stay in the now, trying to stay positive, trying not to have multiple myeloma at the forefront of my thoughts, in everything that I do. And I think MRD negative has played a huge role for me because it has given me some piece of mind that, even if I’m going to relapse, maybe it will be longer. And, hopefully, I’ll stay in remission long enough for another trial to come along for me.

Andrew Schorr:
Yeah. Well, we’ll pray for you exactly that. And I hope so. And I know many of the people watching, and I’ve met a lot of myeloma patients over the years, I’ve been doing these programs since the mid ‘90s.

And, certainly, we’ve lost some people. But so many people are doing better. And there was another treatment waiting for them. And there are others waiting for approval now or close to approval, as we head towards 2019. So, I think learning what’s the right testing, what does it mean, what treatments line up with that, when CAR T, understanding the longevity of that, or who does it work for. And I will just put in a plug for a big meeting coming up. The American Society of Hematology meeting is here in my home county, San Diego. You’ll probably go, Doctor, Tiffany, I’m not sure are you going this year. It would be great to see you.

And so, these studies we’re talking about, trying to answer these questions, it comes out at meetings like that. And there will be a lot of discussion. Who is CAR T right for? What more do we know about MRD testing? When do we do it? What do we do differently because of it? Doctor, did I get it right?

Dr. Manasanch:
Yes, yes, great.

Andrew Schorr:
So, we will be reporting, and my wife Ester and I will be doing some daily wrap ups on the Saturday, Sunday, and Monday of ASH. So, if there’s news about that, we’ll be talking about it. But I think here, we’ve given you a good baseline of where understanding is. So, as we get close to the end here, Tiffany, so people have been listening for 90 minutes. We have a couple of hundred people who have been listening and more. How do people get their head on straight on where this testing and the range of treatment fits better for them? Tiffany, so just help us. Like Cherie was saying, it’s the emotional part of it, with this moving target of myeloma.

Tiffany Richards:
I think I would just tell patients have a discussion with your team about if it’s appropriate for you, at this moment, or if it would be appropriate, in the future. And I think that all of the different response criteria in MRD, I think it’s one of those things that it’s not just going to—they’re not going to be able to really understand it, after just one discussion. I think it’s a continual discussion. And so, I would first say let’s just take it one step at a time. Are you in a very good partial remission? If you are, then, it would be a time to have that conversation about MRD testing or not. If you haven’t gotten to a very good partial remission, let’s just focus on getting you there, rather than looking at the whole entire process, all at the same time.

Andrew Schorr:
Yeah. It’s a lot. And I think, for the family members, often, not Cherie, and not when I was diagnosed with leukemia at 45, that for somebody where, if you’re in your 70s or maybe 80s, and you’re dealing with myeloma, you may have an adult child or a friend helping you make these decisions.

And you feel like you’re kind of drinking from the fire hose, as the treatments have become three, four treatments together, or CAR T, or tandem transplants, or all of these kinds of things, and then, all of the different tests. And the kappa, lambda, and M spike and bands and MRD, it’s a lot to drink in. And you don’t have to feel overwhelmed. How have you—Cherie, would you say knowledge is power? Or having the right healthcare team is part of it? How do you cope when, thank God, there’s more going on in myeloma than ever before?

Cherie Rineker:
Yeah. Knowledge is power, absolutely, a good team that I have at MD Anderson that has been phenomenal, friends’ support.

And knowledge can be a double-edged sword, too. When my last test results came in from MD Anderson, actually, last month, I was so scared to open it because having achieved MRD negativity now, I’m so afraid that the next test is going to show I don’t and that I’ll fall back in that whole thing again. So, like I said, the mental staying mindful and staying positive and just believing in your doctors and your team and knowing that there will be something else on the horizon that can prolong our lives.

Andrew Schorr:
Yeah. And I will tell you, there is a lot going on. But what you know now is you’ve got the little dog that wants your attention. And you’ve got your kids that want your attention. And you’re feeling good today, right?

Cherie Rineker:
Oh, absolutely. Absolutely. I’m beyond grateful. I truly believe that, for me, it was a miracle. I was in a wheelchair last year, and now, I’m out teaching yoga again, incredible.

Andrew Schorr:
Okay. I want to mention that, if you go on the Patient Power site but also on some of you on Facebook groups or whatever, Cherie has written a lot about it. Cherie, what’s the name of your book?

Cherie Rineker:
I have a book, “A Pilgrimage Without End, How Cancer Healed My Broken Heart.” And that kind of ends at when I, in 2016, when I started daratumumab (Darzalex). And I thought that was going to be the end, and I was going to be on that indefinitely. Since, a lot has happened, obviously. So, I’m working on another book now, “Pilgrimage Towards Health, Keeping Hope Alive.” So, I hope sometime in 2019 that will come out. And yeah, now, I’m just advocate and activist and take a lot of questions. Never the doctor questions but more the emotional support that I love to give.

Andrew Schorr:
And raising money for research.

Cherie Rineker:
Yes, I did, for MD Anderson last year, for my 50th birthday, yeah.

Andrew Schorr:
Thank you. Well, we’re so glad that things have worked out. So, doctor, just to wrap up then, this MRD testing that we’ve talked about a lot, along with the other test, is sort of a moving target, right? As is myeloma treatment algorithms, right?

Dr. Manasanch:
Moving target, yes.

Andrew Schorr:
Yes. So, the idea is that patients have the right team. And like you say, you see some patients every month. And it’s an active discussion, right? It’s an iterative discussion.

Dr. Manasanch:
Right.

Andrew Schorr:
So, put it all together though, Doctor. I always like to end this way. Are you hopeful? Because, in the end, what we want to take away as viewers is you’re our barometers. You and Tiffany are our barometers. Knowing what you know, and Tiffany, you said you’ve been doing it 14 years now, right?

Tiffany Richards:
Yeah, 14.

Andrew Schorr:
So, doctor, are you hopeful for those of us who are living with myeloma?

Dr. Manasanch:
Yes, of course. I think that—when I started doing multiple myeloma, all of my patients were doing great. So, this was like 2010, 2011. And it was on clinical trials at NAH with therapy that, at the time, was only given on clinical trials, from the therapy. Everyone was doing great. And I was thinking what is the big deal. Everyone is doing so great. How is this even possible? Like people didn’t used to do well. I think that people have to remember, studies coming out at 2003, the rates of very good partial response and complete remission with therapies, as of 2003, which is 15 years ago, was 10 percent.

And our rate of very good partial response and complete remission right now is, of course, if you do continuous therapy for a year, and most people are in very good partial response or complete remission. So, you went from 10 percent to most patients having it, so now, we’re doing great. I think that we need to figure out why, once we treat it, why it keeps coming back. And I think that’s something that we have not yet figured out yet. And there’s a lot of research trying to find out why. I think that patients will continue to do very well, definitely.

There’s a lot of hope, yeah, definitely. There are so many things that have been going on. There are so many new therapies that are working well. And, again, the self-therapies or the CAR, they’re just the first generation. There are people who are improving on them.

They’re adding things to it. And also, what happens if you give it to someone who has had 10 lines of therapy, but if you give it to someone without a diagnosis? What’s going to happen? We don’t know those things. What if you give it in patients before they develop myeloma? What’s going to happen then? Are you curing them? So, yeah, there are so many things that we can do, right? We don’t have enough—we need more manpower to do all of it. It’s a lot of work. We have a lot of work here, in our department. We have so many things that we want to do. And I think that it’s like the manpower because there’s so much to do.

Andrew Schorr:
Or woman power, there you go.

Dr. Manasanch:
Or women power, but there is so much to do.

Andrew Schorr:
Tiffany, I’m going to let you make the final comment. And that is 14 years there at MD Anderson, right?

Tiffany Richards:
Yep.

Andrew Schorr:
Working in myeloma.

Tiffany Richards:
Yep.

Andrew Schorr:
You’ve seen thousands of patients.

Tiffany Richards:
Yes.

Andrew Schorr:
If somebody comes to you today, obviously, you’ve got to figure out what’s going on. But would you say we can end on a hopeful message?

Tiffany Richards:
Oh, I definitely. So, when I first started 14 years ago, the drugs that were approved that we used—the drugs we had available was bortezomib, thalidomide (Thalomid), transplant, Vad, and melphalan. And that was what we had available to us. And
if you just look at the number of drugs that are now FDA approved for the treatment of myeloma, it’s really remarkable how many options that we have. And every day in clinic, it’s funny because we see these patients every month. And they really do become like part of your family. And I look, and I’ll be like, oh, my gosh, you came right around the same time that I started.
And I’m like oh, my gosh, that was 14 years ago. Wow. And so, there are most definitely reasons to hopeful. And if the
next 14 years are like the last 14 years, then, patients will do really, really well.

Andrew Schorr:
Okay. Amen. All right. I want to thank everybody with us from Houston, Texas today. Cherie Rineker, thank you so much. And all the best to you. Tiffany Richards, thank you. Elisabet Manasanch, thank you so much for being with us. We really explained this in detail. Remember, there will be a replay. And there’s a survey usually we have afterwards. Stay tuned for what we have coming up from ASH. I want to thank the Patient Empowerment Network for pulling all of this together. And I want to thank our financial supporters, Sanofi, Celgene, and AbbVie for supporting the myeloma community. I have a cough I get from a leukemia treatment. In Carlsbad, California, I’m Andrew Schorr. Thank you for joining us. And remember, knowledge can be the best medicine of all.


Please remember the opinions expressed on Patient Empowerment Netowrk (PEN) are not necessarily the views of our sponsors, contributors, partners or PEN. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Measuring My Myeloma With MRD Testing: What Is My Disease State?

Minimal residual disease (MRD) testing is a big topic of interest for many myeloma patients and care partners. What exactly is the role of MRD testing in myeloma, and is it worthwhile?  MRD testing refers to measuring the remaining amount of myeloma cells still in the patients system following therapy resulting in some actionable insights for your healthcare team.

Diagnosed with myeloma in 2012, Cherie Rineker, a young mother to a 13-year-old daughter, learned she was MRD negative two months following her CAR-T treatment. Having been near death, she describes hearing that she was MRD negative as a “miracle and dream come true”—she and her family were overjoyed.  It was in that moment, she felt she might have finally won a battle she has fought for so long. 

On Monday, November 19, 2018 @ 8:30 AM Pacific (10:30 AM Central, 11:30 AM Eastern), join Cherie, Dr. Elisabet Manasanch, an oncologist at MD Anderson Cancer Center and Tiffany Richards, an advanced practice nurse, for an in-depth conversation on how myeloma is being measured to accurately define myeloma disease states.

Join us to learn:

  • What are the advantages of MRD testing, and how is it done?
  • Is MRD testing here to stay?
  • What is MRD negativity vs. positivity?
  • Can MRD testing measure and define my type of myeloma?

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