Tag Archive for: American Society of Hematology

How MPN Researchers Collaborate to Advance Patient Care

How MPN Researchers Collaborate to Advance Patient Care from Patient Empowerment Network on Vimeo.

MPN specialist and researcher Dr. Gabriela Hobbs discusses how collaboration and data sharing among researchers around the world impact MPN treatment advances.

Dr. Gabriela Hobbs is a hematology-oncology physician specializing in the care of patients with myeloproliferative neoplasms (MPN), chronic myeloid leukemia, and leukemia. Dr. Hobbs serves as clinical director of the adult leukemia service at Massachusetts General Hospital. Learn more about Dr. Hobbs.

See More From MPN Clinical Trials 201

Related Programs:

Advancing MPN Research: How Clinical Trials Work

Advancing MPN Research: How Clinical Trials Work

The Risks and Benefits of Participating in an MPN Clinical Trial

The Risks and Benefits of Participating in an MPN Clinical Trial

How Driver Mutation Research Is Advancing MPN Treatments

How Driver Mutation Research Is Advancing MPN Treatments


Transcript:

Katherine:

I’d like to start by discussing your role as an MPN researcher. You’re on the front lines for advancements in the field. What led you to there, and why is it so important to you?  

Dr. Hobbs:

Many things in my life led me to becoming an MPN clinician. First, I wanted to be a clinical investigator since I was very little, and I read a Louis Pasteur book about – you know. And I was fascinated by the fact that you could be both a scientist and a clinician. And after that, I had phenomenal teachers and mentors. And I was really always drawn to patients with hematologic malignancies. I thought that that interaction was very intense and intimate.  

And I was honored to be a part of that interaction. And then from a research perspective and from a scientific perspective, I very clearly remember seeing when the first targeted therapy, Imatinib, was approved when I was an undergrad. And I just thought that was the most fascinating thing. And so, I’ve basically continued to feel that way as I’ve gone through my training, and I’m thrilled to be able to have actually become an MPN clinician so many years later.   

Katherine:

With the American Society of Hematology or ASH meeting taking place this month, it demonstrates how researchers work together around the world to advance care.  

Can you share with the audience how this collaboration works?  

Dr. Hobbs:

Yeah. So, the American Society of Hematology meeting – or the ASH meeting – is really one of my favorite events of the year.  

And it really highlights what you said. It is such a positive environment, and it’s so exciting to use that opportunity to talk to my collaborators from across the globe. And I really think that that’s where the scientific community shines because really all of us are actually trying to figure out how to work together and overcome sometimes a lot of obstacles – bureaucratic obstacles, regulatory obstacles – to make sure that we can share data, do it the right way. But really we always have one thing in mind.  

And that is to be able to advance the care that we give our patients. And so, that collaboration and really that collaborative environment is always very positive. And I always come back home very energized from that. And then just seeing all my colleagues presenting all the wonderful things that they are working on and getting updates on their research is just an exciting environment.   

 Katherine:

In your view, why is it essential to present and share data at these larger conferences like ASH? 

Dr. Hobbs:

So, for many different reasons. I mean, there are many different ways of presenting data that can be done through just publishing a paper. But the nice thing about conferences – and especially large conferences – is that you really get an opportunity to present work in progress. And some of these research projects may not end up turning into bigger projects or they may not become bigger trials. But all of them have at least an opportunity to learn something from them, whether or not they worked or they didn’t work.   

Oftentimes when things are published in journals, especially the high-impact journals, we are seeing trials that had positive results. But sometimes we don’t see those smaller trials that never went anywhere. And so, having a forum when we can discuss work that’s ongoing, discuss about projects that are maybe having issues, all those things actually really help us to change our research questions or develop new research questions based on what’s working and also really what’s not working. And so, having this large forum to present all of that data, I think, is really, really important to helping us design future clinical trials and projects. 

Updates in CAR T-Cell Therapy for Myeloma From ASH 2021

Updates in CAR T-Cell Therapy for Myeloma from ASH 2021 from Patient Empowerment Network on Vimeo.

Myeloma specialist, Dr. Omar Nadeem, shares the latest updates in CAR T-cell therapy from the 2021 American Society of Hematology (ASH) annual meeting. Dr. Nadeem discusses long-term study results and optimism for the future of CAR T-cell therapy.

Dr. Omar Nadeem is the Clinical Director of Myeloma Cellular Therapies Program and Director of Myeloma and Plasma Cell Pathways at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem, here.

See More from Thrive Myeloma


Related Programs:

The Latest in Myeloma Research: Updates from ASH 2021

The Latest in Myeloma Research: Updates from ASH 2021

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

How Could Clinical Trials Fit Into Your Myeloma Treatment Plan?

An Expert’s Hopeful Outlook on Myeloma Research and Treatment

An Expert’s Hopeful Outlook on Myeloma Research and Treatment 


Transcript:

Dr. Nadeem:

My name is Omar Nadeem, and I’m at the Dana Farber Cancer Institute in Boston, Massachusetts. I’m an instructor of medicine at Harvard Medical School, and I direct the myeloma cellular therapies program at Dana Farber.

Katherine:

Dr. Nadeem, you’ve joined us from the American Society of Hematology Meeting in Atlanta. Can you share any highlights in myeloma from the meeting?

Dr. Nadeem:

Yeah, it’s a very exciting time in myeloma therapeutics. We’re seeing a lot of new agents that are being reported at this meeting, showing very promising results.

Then we’re also fine tuning the way we treat myeloma patients by looking at different combinations in all lines of therapy, whether it be front-line or relapsed setting, to try to really understand which treatments are the best and then also more importantly, which treatments do we need to continue patients on, etcetera as they’re going through their myeloma journey. So, lots of updates with important trials at this meeting so far.

Katherine:

We’re hearing a lot about the promise of CAR T-cell therapy. Is there any research news in CAR T-cell for myeloma treatment?

Dr. Nadeem:

Yeah. So, we’ll have a presentation later today, actually, updated results of the CARTITUDE-1 study, which is looking at cilta-cel, which is an anti-BCMA directed CAR-T cell product.

And this trial is a phase-1/2 study looking at some patients with relapse in refractory multiple myeloma that has been reported previously to have a very, very high response rate and very high rates of MRD negativity.

So at this meeting, with just longer follow-up, which is what we’re looking for in terms of how long these responses last, we’re starting to see that the median duration of response is now almost 22 months, which is very impressive looking at the data and comparing it to some of the other CAR-T products that are either under study or the one that’s currently approved.

So, that looks very promising. And also notably, we had some concerns initially about toxicity with this particular product. But that really hasn’t been seen with longer follow-up. So, we’re not seeing a toxicity signal, particularly as it relates to neurological toxicity, with the longer follow-up. So, that presentation will be later today. We look forward to seeing the updates, but so far this looks very encouraging and this is what we anticipate to be the next product that’s available in the market for myeloma.

Updates from ASH: How Biomarker Testing Has Changed MPN Care

Updates from ASH: How Biomarker Testing Has Changed MPN Care from Patient Empowerment Network on Vimeo.

MPN specialist, Dr. Andrew Kuykendall, discusses how the identification of specific biomarkers in myeloproliferative neoplasms (MPNs), such as the JAK2 mutation, have moved research forward. Dr. Kuykendall shares promising findings that were released at the 2021 American Society of Hematology (ASH) annual meeting and how this may impact MPN care in the future.

Dr. Andrew Kuykendall is an Assistant Member at Moffitt Cancer Center in the Department of Malignant Hematology. Dr. Kuykendall’s clinical and research efforts focus on myeloproliferative neoplasms (MPNs), MDS/MPN overlap syndromes and systemic mastocytosis (SM). Learn more about Dr. Kuykendall, here.

See More from INSIST! MPNs

Related Programs

The Latest in MPN Research: Updates from ASH 2021

The Latest in MPN Research: Updates from ASH 2021

Which Gene Mutations Impact Myelofibrosis Treatment Options?

Which Gene Mutations Impact Myelofibrosis Treatment Options?

Which Tests Do You Need Following an MPN Diagnosis

Which Tests Do You Need Following an MPN Diagnosis? 


Transcript

Katherine:

How has molecular or biomarker testing changed the field of MPN care and treatment?

Dr. Kuykendall:

Well, I think, first and foremost just understanding – going back to 2005 and knowing that we have JAK2 mutations. I think that gave really a lot of clarity to the diagnosis and really understanding the biology of how the disease acted through the JAK-STAT pathway. And certainly, that led to the understanding of MPL mutations and then calreticulin mutations.

We’re still figuring out exactly how calreticulin mutations work. There was a great abstract, a preclinical abstract, this year talking about the impact of interferon on calreticulin mutations and how that may differ from what we see in the impact of interferon on diseases that are driven by JAK2 mutations.

Clinically, we see a little bit of difference in how those diseases respond and we may understand a little bit better about why that happens. Additionally, that’s kind of gone down to looking at these big next generation sequencing panels where we identify high-risk mutations and that can certainly change our understanding of the prognosis of these diseases.

We’re starting to get, at least in the AML world, we’re getting targeted agents that can potentially target some of these mutations such as IDH1 and IDH2 mutations that have specific inhibitors.

Those are mutations that occur in myeloproliferative neoplasm patients and convey a worse prognosis, so there are ongoing trials looking to see if we can use those IDH inhibitors in myeloproliferative neoplasms either in the chronic phase or maybe in the more accelerated advanced phase.

You know the big thing, this meeting, was actually looking at polycythemia vera patients and what’s the relevance of the JAK2 mutant allele burden. I think this is something we’ve talked about a lot as far as how significant this is. We know in chronic phase myeloproliferative neoplasms that that JAK2 mutation tends to be associated with more thrombotic complications.

There are more blood clots in the veins and the arteries. There were a couple great abstracts that looked at the really the implications of the JAK2 mutation and the fact that it is associated with more thrombosis, but maybe more venous thrombosis. That might be a big risk factor for venous thrombosis and it may be that cardiovascular risk factors, such as diabetes, hyperlipidemia that’s really what’s driving the arteriole thrombosis. It also looked at the variant allele fraction, the number of cells that have that JAK2 mutation.

One abstract showed that if you have over a 50 percent allele fraction, if more than 50 percent of the alleles have the mutation – a higher burden of that mutation that’s associated with an increased thrombotic risk even in low-risk polycythemia vera patients. Whether or not that’s enough evidence to really change the paradigm of how we treat low-risk patients is to be determined, but I think very interesting and provocative work. 

Expert Advice for Finding an MPN Clinical Trial

Expert Advice for Finding an MPN Clinical Trial from Patient Empowerment Network on Vimeo.

Dr. Andrew Kuykendall, an MPN specialist and researcher, shares tips for learning about available clinical trials. Dr. Kuykendall emphasizes the importance of seeking a consultation with a specialist and suggests questions to ask your provider about clinical trials.

Dr. Andrew Kuykendall is an Assistant Member at Moffitt Cancer Center in the Department of Malignant Hematology. Dr. Kuykendall’s clinical and research efforts focus on myeloproliferative neoplasms (MPNs), MDS/MPN overlap syndromes and systemic mastocytosis (SM). Learn more about Dr. Kuykendall, here.

See More from INSIST! MPNs

Related Programs

The Latest in MPN Research: Updates from ASH 2021

The Latest in MPN Research: Updates from ASH 2021

Updates from ASH: How Biomarker Testing Has Changed MPN Care

MPN Research and Optimism About Curative Therapies-2

MPN Research and Optimism About Curative Therapies

 


Transcript

Katherine:

How can patients find out about clinical trials? Are there specific questions that they should be asking their doctors about to participate in a trial?

Dr. Kuykendall:

Yeah. I think it’s tough. One way – there are a few different tools that I would recommend. One, if you’re very interested in just what trials are going on you can go to this national cancer trials, or NCT, network and try to understand online what trials are available. Clinicaltrials.gov is the actual website but that’ll show you the ongoing clinical trials that are there.

You can type in a disease state, so you can type in polycythemia vera or myelofibrosis or essential thrombocythemia, and it’ll give you a huge list of all the trials that are there. It can be kind of overwhelming because it’ll list all of the trials that have ever been done, but there are different ways that you can stratify those results and look for trials that are just recruiting that are active and that’ll taper down that list. And when you click on those trials there usually is at the bottom a list of participating centers that are there. So, you can see the different centers that are there. Overall, I think that that is a very broad way of doing it and somewhat complicated.

What I would ask is – and one of the things that we always push for is – while most of these myeloproliferative neoplasms can be treated quite easily in the community, meaning that the actual mechanisms of what’s being provided is not something that requires a specialized center. I think the understanding of the disease really does. We always recommend having someone in your corner who’s an expert. They don’t have to be the one who is most involved in your care but having someone in your corner who’s an expert.

That’s the person who’s going to know what trials are going on, what trials may be coming down the pipeline, where those trials may be occurring, and they might also tell you “Okay, here are the things that would prompt you to maybe want a trial.” I had a lot of patients that were surprised to realize there were trials available just because they had – they were getting six or seven phlebotomies a year. They were complaining about that but they figured that was just the ways things were. Lo and behold, there was actually a trial that was ongoing that was trying to reduce the need for those phlebotomies in otherwise low-risk patients.

You can always go to clinicaltrials.gov but also try to ask your doctor about hey is there, if you haven’t seen an expert, is there someone close by an expert that I can see for a second opinion just to understand the disease and ask about trials. Usually everyone’s okay with that and when you do see an expert, say “Hey, first of all what trials are right for me now and what in the future might be reasonable and how am I going to know and how often should I check in to see what things are available?” 

The Latest in MPN Research: Updates from ASH 2021

The Latest in MPN Research: Updates from ASH 2021 from Patient Empowerment Network on Vimeo.

MPN specialist, Dr. Andrew Kuykendall, shares the latest news from the 2021 American Society of Hematology (ASH) annual meeting. Dr. Kuykendall discusses the latest findings in MPN research, including an update on JAK inhibitors, advances in BET inhibitors, as well as a new therapy in development aimed at reducing phlebotomy in patients with polycythemia vera (PV).

Dr. Andrew Kuykendall is an Assistant Member at Moffitt Cancer Center in the Department of Malignant Hematology. Dr. Kuykendall’s clinical and research efforts focus on myeloproliferative neoplasms (MPNs), MDS/MPN overlap syndromes and systemic mastocytosis (SM). Learn more about Dr. Kuykendall, here.

See More from INSIST! MPNs

Related Programs

MPN Research and Optimism About Curative Therapies-2

MPN Research and Optimism About Curative Therapies

Expert Advice for Finding an MPN Clinical Trial

Expert Advice for Finding an MPN Clinical Trial

An Overview of ET, PV and MF Treatment Options

An Overview of ET, PV and MF Treatment Options 


Transcript

Katherine:

You’re joining us following the American Society of Hematology Meeting where cancer researchers came together to share their findings. Are there highlights from the meeting that patients should know about?

Dr. Kuykendall:

Yeah, absolutely. So, the meeting we just came from, the so-called ASH meeting, is really an annual meeting. Happens every December.

It’s really a chance for researchers to share their most exciting findings and really what they’ve been working on for the past few years, and certainly in the past year.

As a clinical researcher, I think I have always a keen interest in clinical trials that are going to give us some new data so we can see how things are working, but I think this is also a big meeting for pre-clinical studies for basic scientists who get to share what’s exciting in their labs. A lot of times that’ll give a preview of what’s to come maybe four, five years down the road what we’ll see on the clinical side. From the clinical side, which is more in my realm, there is certainly a few specific things to get excited about. Within the field of myeloproliferative neoplasms, we have polycythemia vera, ET – essential thrombocythemia, myelofibrosis.

And on the myelofibrosis side of things, I think we continue to get excited about just really the proliferation of drugs that are in late-stage clinical trials. This meeting was no different from that.

We started to get a little bit more clarity as far as this agent, pelabresib, which is a BET inhibitor which is being looked at really in a variety of different settings as a single agent in combination with ruxolitinib (Jakafi) and as an add-on to ruxolitinib as well.

This was another exciting need to get an update on where the data looks to be with pelabresib. Certainly, there’s an ongoing Phase III study in the up-front setting with that agent. We’re anxiously awaiting results too. Additionally, we’ve got more information regarding other JAK inhibitors that may be coming down the pipeline in the coming months to years with momelotinib and pacritinib.

Certainly, that’s always exciting to see the data come from there, especially when we get kind of further along in their trials, we start to get very isolated assessments of their data. Looking specifically at transfusion rates and the efficacy within the subpopulations that have unmet need. And so, I think that that’s always exciting.

I think polycythemia vera – this is a really big meeting for polycythemia vera. We obviously know that ropeginterferon (Besremi) just got FDA-approved in November.

We also started to see the updated data with rusfertide, or PTG-300, which is a hepcidin memetic that aims to reduce phlebotomy rates in patients that are requiring a ton of phlebotomies which, as we know, can be very impactful on quality of life having to get recurrent phlebotomies.

I think that those were the really big highlights, and the take-aways from this is really we are starting to see these agents move into the late-stage clinical trials.

AML Research Updates: News from ASH 2020

AML expert Dr. Jeffrey Lancet shares news from the 2020 American Society of Hematology (ASH) annual meeting. Dr. Lancet sheds light on headlines from the meeting including FLT3 inhibitor research, combination therapies with venetoclax, a promising inhibitor therapy, and shares his optimism about the future of AML treatment.

About the Guest:
Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

See More From INSIST! AML


Transcript

Katherine:

Hello and welcome, I’m Katherine Banwell. Today we’ll discuss the latest news from ASH 2020 and how AML patients can advocate for personalized care. Joining me is Dr. Jeffrey Lancet. Welcome, would you please introduce yourself?

Dr. Lancet:

Hi, sure. My name is Dr. Jeff Lancet. I’m at the Moffitt Cancer Center in Tampa, Florida where I am the Chair of the Malignant Hematology Department. We spend a lot of time treating patients and conducting clinical trials of Acute Myeloid Leukemia.

Katherine:

Dr. Lancet, the American Society of Hematology annual meeting just closed. What are the AML headlines from this year’s meeting?

Dr. Lancet:

Yeah, so as usual AML was a very busy area for clinical presentations this year at the ASH meeting focusing largely on novel and targeted therapies. I don’t believe that there were many practice changing delevelopments, per se, but rather discussions about many promising therapeutic strategies that are still under development and moving forward rapidly largely in the areas of targeted therapy, low intensity therapy, measurable residual disease, and things of that nature.

Katherine:

What does this research news mean for patients?

Dr. Lancet:

Well, I think that there is a lot to be encouraged about and maybe I’ll take the time to review some of the highlights in what was presented with respect to some of the novel therapeutic approaches that many of our patients can look forward to receiving in the not-too-distant future.

So we often talk about targeted therapy instead of, of course, one of the major targets over the years has been that of a mutated FLT3, which is one of the most common mutations in AML.

And at this meeting, we saw several presentations on clinical trials results utilizing Inhibitors of FLT3 with some emphasis on the most recently approved 2nd generation drug called gilteritinib.

There were, I thought, three major presentations focusing on gilteritinib. One was an update on a randomized phase 3 trial comparing gilteritinib plus azacitidine versus azacitidine alone in newly diagnosed unfit for induction chemotherapy patients with FLT3 mutations. Preliminary showing good tolerability and high composite complete response rates in the combination arm. 

There was another trial of gilteritinib plus venetoclax in relapsed refractory FLT3 mutated AML and what was interesting was that a very high percentage of patients achieved response with this combination of gilteritinib plus venetoclax. Many of whom were heavily pre-treated previously and many of whom had also got prior FLT3 inhibitor therapy during an earlier stage of the disease, so the combination of gilteritinib plus venetoclax in this more refractory setting was encouraging to see these promising responses.

And then we say some data reporting the effects of gilteritinib in combination with more traditional chemotherapy induction with a couple of studies demonstrating both high complete response rates, as well as high rates of mutation clearance of the FLT3 mutation. So those are very encouraging data that were presented with respect to the FLT3 mutated AML population. 

So another very important drug that reached the marketplace for AML recently is a drug called venetoclax, which is an inhibitor of a protein called BCL2. And this drug was recently FDA approved for use in combination with low-intensity chemotherapy drugs such as azacitidine or decitabine. And it seems as though the combination of venetoclax plus one of these hypomethylating agent drugs, azacitidine or decitabine, has resulted in very strong efficacy signals as recently published in the New England Journal of Medicine paper that reported on the results of the Phase 3 trial of venetoclax plus azacitidine.

So that has now become standard of care for older, less fit adults with newly diagnosed AML. The combination of venetoclax plus hypomethylating agent such as azacitidine. And naturally there’s been interest in really kind of taking it several steps further to advance the role of these combinations and to also look at additional drugs in combination with venetoclax plus hypomethylating agent therapy. So, we saw some of that at the ASH meeting this year.

One approach would be to take venetoclax and then to combine it with more intensive chemotherapy for perhaps more fit patients or younger patients that could undergo a more intensive program. So we saw presentations of venetoclax being combined with a drug called CPX-351 which is a novel liposomal formulation of two common chemotherapy drugs that had been approved a few years ago for secondary AML. And we also saw a combination strategy with venetoclax and a regimen known as FLAG-IDA, which is a commonly used induction regimen in Acute Myeloid Leukemia.

I think it’s important to recognize that although these trials they combine venetoclax with more intensive chemotherapy show signs of good efficacy with good response rates, there are definitely signals of increased toxicity, hematologic toxicity, primarily. Which is not really unexpected with venetoclax knowing that it can cause significant lowering of white blood cells, platelets, and hemoglobin.

Then finally, there is a lot of interest in doing these types of combinations with venetoclax in different subsets of AML. And one subset of AML that has been very important recently is that of the IDH-mutated AML population of patients. IDH is a fairly common mutation that occurs in either in the form of IDH1 or IDH2, and there’s about a 15-20% incidence of IDH mutations in AML. Though we do have an inhibitor for both of these types of mutations, ivosidenib for IDH1 and enasidenib for IDH2, but there also appears to be a strong role for venetoclax plus azacitidine in IDH mutated AML. We saw from a series of patients presented by a physician at MD Anderson looking at outcomes with venetoclax plus azacitidine in IDH mutated AML. The response rates were very high when you give HMA plus venetoclax to these patients with IDH mutated AML. But, I think more importantly, is that there were what we call high intra-patient response rates when switching between venetoclax and HMA therapy with IDH inhibitor continued regimen. In other words, a patient would have a good chance of responding to the initial therapy, then, if or when that therapy stops working, having a good effect from the salvage therapy with the other regiment, So if you received initially azacitidine plus venetoclax, and then had a relapse, the IDH inhibitors worked well and vice-versa if have received an IDH inhibitor, then subsequently received HMA/venetoclax at a later time point, that also worked well.

So it’s encouraging to see that you can potentially sequence these drugs and get continued responses along the way that ultimately we think that will help survival and keep patients in a better state of health for longer.

So I just wanted to take a few minutes also and discuss some of the newer more novel therapies that are really hitting or approaching the landscape right now. One of these is called CC-486, also known as oral azacitidine or onureg, and this drug was shown in a recent literature to prolong overall survival in patients who are in first remission from their AML who had received induction chemotherapy. So this drug was used as maintenance therapy after a variable number of consolidation regimens and people who got this onureg or azacitidine drug as maintenance therapy, it resulted in longer survival compared to those who had received placebo. This was presented at last year’s ASH meeting, but this year’s ASH meeting provided an update, a very important update, showing that the overall survival advantage from this drug, this oral azacitidine drug, when used as maintenance was independent of whether a patient had measurable residual disease at the time that they went on to the maintenance therapy. In other words, whether you had MRD (measurable residual disease) or not at the time of the study entry, your responses were still more favorable, your outcomes were more favorable if you received this oral azacitidine drug. So this was FDA approved earlier this year for patients in the maintenance phase of therapy for AML who had got prior induction chemotherapy. 

And importantly, this drug was also shown to be able to convert about 25% of patients who were positive for measurable residual disease, to convert them from positive to negative. So even though they were in remission, they had measurable residual disease and this drug in about 25% of the cases converted them from positive to negative. So that’s a very important finding as well. 

Another important drug that I think you should keep your eye on is a drug called magrolimab. This is an antibody against a certain type of protein that is present on an immune system cell called the macrophage. And when this magrolimab drug is combined with azacitidine in a recent clinical trial, it was demonstrated very high response rates of over 65%, and in particular in patients with P53 mutation, which is a very bad mutation to have in most cancers including AML. In patients with this high-risk mutation, the combination magrolimab with azacitidine appears to be effective based on the early data that we have with high response rates.

And then finally, I just wanted to make mention of another important area in, not really just AML, but all cancer, and that’s outcomes disparities between different races and ethnic groups. And we saw a very important presentation at the plenary session this year where the authors reported outcomes amongst younger patients with AML who are African American compared with caucasion. And the data clearly indicated a worse overall survival amongst black patients compared to white patients under age 60. And this included patients who are enrolled in clinical trials. So that, it appeared that African American patients had a worse outcome than Causian patients with Acute Myeloid Leukemia. Highlighting the need to better understand various risk factors and other factors that play into these disparate outcomes between our black American population and our white American population, which I think could shed light on additional disease characteristics that many help everybody.

Katherine:

Dr. Lancet, thanks so much for joining us today

Dr. Lancet:

Thank you very much for having me. It was good to be with you.

Katherine:

And thank you to our audience, I’m Katherine Banwell.


Don’t miss an episode and subscribe to PEN’s Empowered! Podcast wherever podcasts are available.

Staying Updated on AML Research News: Advice from an Expert

Staying Updated on AML Research News: Advice from an Expert from Patient Empowerment Network on Vimeo.

Dr. Jeffrey Lancet, an AML expert from Moffitt Cancer Center, shares tips for sifting through research news and encourages communication with your healthcare team about what you’ve learned.

Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

Essential Testing in AML: How Results Impact Care & Treatment Choices

Navigating AML Treatment Decisions

Key AML Testing for Better Care: Understanding Prognosis and Treatment Choices

Transcript:

Katherine:      

Well, patients are often educating themselves about developing research and new treatment options. Do you have advice for patients who, when it comes to talking with their doctors about what they’ve learned?

Dr. Lancet:                   

I think it’s important for patients to speak to their doctors directly and as soon as possible as opposed to going on the internet and doing a Google search for this drug or that because every patient’s situation is unique and how to apply these new drugs is very different amongst patients.

And some patients may qualify for certain approaches and others do not. So, it’s very important to talk to your doctor about how you can individualize your treatment based upon your specific scenario. What type of mutation does a patient have, what is their level of fitness, are they potentially candidates for bone marrow transplant? Those are some of the basic questions that come up all the time to determine what is the best treatment approach.

And as we’re developing new therapies, and more of them, there will be more options for patients and a more personalized approach that can be taken that really can only be decided based upon that individual patient’s unique profile. So, it’s very important to really recognize that one size does not fit all when it comes to treatment of this disease and that certain drugs may be helpful and certain drugs may be unhelpful in that particular site.

Katherine:                   

What would you like to leave patients with today? Are you hopeful about the future of AML treatment and research?

Dr. Lancet:                   

Yes, I’m very hopeful. I think AML is a disease that is really a very diverse and complex one. It doesn’t lend itself well to huge immediate breakthrough therapies that will immediately change the landscape by double digit percentages for example. This is a disease that, again is very complex, and in which advances are made slowly but steadily. And I think we’ve seen that over the past to 5 to 10 years is that we are gradually incorporating new drugs into our treatment regimens with gradually increasing levels of success as we learn more about these drugs starting out as single agents and then beginning to combine them.

I think that we’re learning an awful lot about the molecular landscape about AML and how it impacts treatments and treatment decisions and prognoses. I think our ability now to detect what we recall measurable residual disease is very important. Also, because now we can get a grasp of how well our treatments are working and are we knocking out enough bad cells to expect good outcomes, and if we’re not, then hopefully we can intervene and kind of hit it while it’s down so to speak and use some of these new therapies to knock out what might be left over to give patients better overall long term responses and results.

So, definitely reason to be hopeful, but we have to stay patient as well. It’s difficult because it’s a, it’s a terrible disease but we have to recognize that it’s something that requires very careful research to develop the appropriate clinical trials that will have the highest chance of success.

Katherine:                   

Dr. Lancet, thanks so much for joining us today.

Dr. Lancet:                   

Thank you very much for having me. It was good to be with you and I appreciate the opportunity.

Katherine:

And thank you to our audience. I’m Katherine Banwell.

 

 

 

AML Research Updates: News From ASH 2020

AML Research Updates: News from ASH 2020 from Patient Empowerment Network on Vimeo.

AML expert Dr. Jeffrey Lancet shares the latest news from the 2020 American Society of Hematology (ASH) annual meeting. Dr. Lancet sheds light on headlines from the meeting including FLT3 inhibitor research, combination therapies with venetoclax, a promising inhibitor therapy, and shares his optimism about the future of AML treatment.

Dr. Jeffrey Lancet is Chair and Program Lead in the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, FL. He is nationally and internationally recognized for his clinical research in the field of acute leukemias. Learn more about Dr. Lancet, here.

Download Program Resource Guide

See More From INSIST! AML

Related Resources:

Navigating AML Treatment Decisions

New AML Therapies vs. Traditional Chemotherapy: What’s the Difference?

Transcript:

Katherine:      

Hello, and welcome. I’m Katherine Banwell. Today we’ll discuss the latest news from ASH 2020 and how AML patients can advocate for personalized care. Joining me is Dr. Jeffrey Lancet. Welcome. Would you please introduce yourself?

Dr. Lancet:                   

Hi, sure. My name is Dr. Jeff Lancet. I’m at the Moffitt Cancer Center in Tampa, Florida, where I am the Chair of the Malignant Hematology Department. We spend a lot of time treating patients and conducting clinical trials of Acute Myelogenous Leukemia.

Katherine:                   

Okay. Thank you. Dr. Lancet, the American Society of Hematology Annual Meeting just closed. What are the AML headlines from this year’s meeting?

Dr. Lancet:                   

Yeah, so as usual, AML was a very busy area for clinical presentations this year at the ASH meeting focusing largely on novel and targeted therapies.

I don’t believe that there were many practice changing developments per se, but rather discussions about many promising therapeutic strategies that are still under development and moving forward rapidly largely in the areas of targeted therapy, low intensity therapy, measurable residual disease and things of that nature.

Katherine:                   

What does this research news mean for patients?

Dr. Lancet:                   

Well, I think that there’s a lot to be encouraged about and maybe I’ll take the time to review some of the highlights in what was presented with respect to some of the novel therapeutic approaches that many of our patients can look forward to receiving in the not too distant future.

So, we often talk about you know, targeted therapies and, of course, one of the major targets over the years has been that of mutated FLT3 which is one of the most common mutations in AML.

And at this meeting we saw several presentations on clinical trials resolved to utilizing inhibitors of FLT3, with some emphasis on the most recently approved second generation drug called gilteritinib.

There were I thought three major presentations focusing on gilteritinib and one was an update on a randomized Phase III trial comparing gilteritinib plus azacitidine versus azacitidine alone in newly diagnosed unfit for induction chemotherapy patients with FLT3 mutations, preliminarily showing good tolerability and high composite complete response rates in the combination on.

There was another trial of gilteritinib plus venetoclax in relapsed and refractory FLT3 mutated AML.

And what was interesting was that a very high percentage of patients achieved response with this combination of gilteritinib plus venetoclax, many of whom were heavily pretreated previously and many of whom had also gotten prior FLT3 inhibitor therapy during an early stage of the disease. So, the combination of gilteritinib and venetoclax and this more refractive study, it was encouraging to see these promising responses.

And then we saw some data reporting the effects of gilteritinib in combination with more traditional chemotherapy induction with a couple of studies demonstrating both a high complete response rates as well as high rates of mutation clearance of the FLT3 mutation.

So, those were very encouraging data that were presented with respect to the FLT3 mutated AML population.      

So, another very important drug that reached the marketplace for AML recently is a drug called venetoclax, which is an inhibitor of a protein called BCL2.

And this drug was recently FDA approved for use in combination with low intensity chemotherapy drugs such as azacitidine or decitabine.

And it seems as though the combination of venetoclax plus one of these hypomethylating agent drugs, azacitidine or decitabine has resulted in very, very strong efficacy signals as recently published in a New England Journal of Medicine paper that reported on the results of the Phase III trial of venetoclax plus azacitidine.

So, that has now become standard of care for older less fit adults with newly diagnosed AML; the combination of venetoclax plus a hypomethylating agent such as azacitidine.

And naturally, there’s been interest in really kind of taking it several steps further to advance the role of these combinations and to also look at additional drugs in combination with venetoclax plus hypomethylating agent therapy.

So, we saw some of that at the ASH meeting this year. One approach would be to take venetoclax and then to combine it with more intensive chemotherapy for perhaps more fit patients or younger patients that could undergo a more intensive program.

So, we saw presentations of venetoclax being combined with a drug called CPX-351, which is a novel liposome formulation of two common chemotherapy drugs that had been approved a few years ago for secondary AML. And we also saw a combination strategy with venetoclax, and a regimen known as FLAG-IDA, which is a commonly used induction regimen in acute myeloid leukemia.

And I think it’s important to recognize that although these trials that combine the venetoclax with more intensive chemotherapy showed signs of good efficacy with good response rates, there were definitely signals of increased toxicity, hematologic toxicity primarily, which is not completely unexpected with venetoclax knowing that it can cause significant lowering of white blood cells and platelets and hemoglobin.

And then finally, there is a lot of interest in, you know, doing these types of combinations with venetoclax in different subsets of AML and one subset of AML that has been very important recently is that of the IDH mutated AML population of patients.

IDH is a fairly common mutation that occurs either in the Isoform of IDH1 or IDH2 and there’s about a 15 to 20 percent incidence of IDH mutations in AML.

Now we do have an inhibitor for both of these types of mutations: ivosidenib for IDH1 and enasidenib for IDH2, but there also appears to be a strong role for venetoclax plus azacitidine in IDH mutated AML.

We saw from a series of patients presented by a physician at MD Anderson looking at outcomes with venetoclax plus azacitidine in IDH mutated AML. And the response rates were very high when you give HMA plus venetoclax to these patients with IDH mutated AML.

But I think more importantly was that there were what we call high intro patient response rates when switching between venetoclax and HMA therapy with an IDH inhibitor containing regimen.

In other words, a patient would have a good chance of responding to the initial therapy and then if or when that therapy stops working, having a good effect from a salvage therapy with the other regimen. So, when you see initially azacitidine plus venetoclax and then had a relapse, the IDH inhibitors worked well and vice versa if you had received an IDH inhibitor and then subsequently received HMA-venetoclax at a later time point that also worked well.

So, it’s encouraging to see that you can potentially sequence these drugs and get continued responses along the way and ultimately we think will help a survivor and keep patients in a better state of health even longer.               

So, I just wanted to take a few minutes also and discuss some of the newer more novel therapies that are really hitting or approaching the landscape right now. One of these is called CC486, also known as oral azacitidine or ONUREG. And this drug was shown in recent literature to prolong overall survival in patients who are in first remission from their AML who had received induction chemotherapy.

So, this drug was used as maintenance therapy after a variable number of consolidation regimens. And people who got this ONUREG or oral azacitidine drug as maintenance therapy, it resulted in longer survival compared to those who had received placebo.

And this was presented at last year’s ASH meeting, but this year’s ASH meeting provided an update, a very important update, showing that the overall survival advantage from this drug, this oral azacitidine drug, when used as maintenance was independent of whether a patient had measurable residual disease at the time that they went onto the maintenance therapy.

In other words, whether you had MRD, measurable residual disease or not at the time of the study entry, your responses were still more favorable, your outcomes were more favorable, if you received this oral azacitidine drug.

So, this was FDA approved earlier this year for patients in the maintenance phase of therapy for AML who had gotten prior reduction chemotherapy.

And importantly, this drug was also shown to be able to convert about 25% of patients who were positive for measurable residual disease; convert them from positive to negative. So, even though they were in remission, they had measurable residual disease and this drug in about 25 percent of the cases converted that from positive to negative. So, that’s a very important finding as well.

Another important drug that I think you should keep your eye on is a drug called magrolimab. This is an antibody against a certain type of protein that is present on the immune system cell called the macrophage, and when this magrolimab drug was combined with azacitidine in a recent clinical trial, it was demonstrated very high response rates of over 65 percent.

And, in particular, in patients with P53 mutations, which is a very bad mutation to have in most cancers, including AML, in patients with this high-risk mutation, the combination of magrolimab with azacitidine appears to be effective based upon the early data that we have with high response rates.

And then finally, I just wanted to make mention of another important area in, not really just AML, but in all cancer and that’s  outcomes disparities between different races and ethnic groups. And we saw a very important presentation at the plenary session this year where the authors reported outcomes amongst younger patients with AML who were African American compared with Caucasian.

And the data clearly indicated a worse overall survival amongst Black patients compared with white patients under age 60. And this included patients who were enrolled in clinical trials. So, that it appeared that African American patients have a worse outcome than Caucasian patients with acute myeloid leukemia highlighting the need to better understand various risk factors and other factors that play into these disparate outcomes between our Black American population and a white American population, which I think could shed light on additional disease characteristics that may help everybody as well.

 

2020 ASH Annual Meeting

Mark your calendar for the world’s most comprehensive hematology event of the year, the 62nd ASH Annual Meeting and Exposition – originally to be held in San Diego, California – will be presented as an all-virtual event, given the continuing threat of the COVID-19 pandemic.

The meeting will provide an invaluable educational experience and the opportunity to review thousands of scientific abstracts highlighting updates in the hottest topics in hematology. Network with top minds in the field and a global community of more than 30,000 hematology professionals from every subspecialty.

ASH 2019: Multiple Regimens, Deeper Responses in Multiple Myeloma Treatment

 

Dr. Sikander Ailawadhi of Mayo Clinic provides high-level highlights for multiple myeloma from the 61st American Society of Hematology (ASH) Meeting in Orlando, Florida.

About Diverse Health Hub:

Diverse Health Hub is a health equity education and awareness channel producing educational content for both patients and providers in order to bridge the gaps between healthcare practices and the needs of multicultural communities.  Diverse Health Hub works directly with a diverse patient and respected provider population in multiple therapeutic areas to promote cultural competence in healthcare. The organization believes access to these diverse perspectives cultivates culturally competent communities.

Related Programs:

Good News for Future of Myeloma Treatment, Still Addressing Race-Associated Risks

ASH 2019: Disparities Around Accessing Health Technology Revealed for a Subset of Myeloma Patients

ASH 2019: Disparities Around Accessing Health Technology Revealed for a Subset of Myeloma Patients

In this Diverse Health Hub interview, Dr. Sikander Ailawadhi of Mayo Clinic, discusses disparities around access to care in multiple myeloma from the 61st American Society of Hematology (ASH) Meeting in Orlando, Florida.

About Diverse Health Hub:

Diverse Health Hub is a health equity education and awareness channel producing educational content for both patients and providers in order to bridge the gaps between healthcare practices and the needs of multicultural communities.  Diverse Health Hub works directly with a diverse patient and respected provider population in multiple therapeutic areas to promote cultural competence in healthcare. The organization believes access to these diverse perspectives cultivates culturally competent communities.

Related Programs:

Good News for Future of Myeloma Treatment, Still Addressing Race-Associated Risks

ASH 2019: Multiple Regimens, Deeper Responses in Multiple Myeloma Treatment

Good News for Future of Myeloma Treatment, Still Addressing Race-Associated Risks

Respected myeloma expert, Dr. Ajay Kumar Nooka, provides an update from the 61st American Society of Hematology (ASH) meeting. Dr. Nooka shares why this is a good time in myeloma research and the important work that remains around myeloma treatment disparities for people of color.

About Diverse Health Hub:

Diverse Health Hub is a health equity education and awareness channel producing educational content for both patients and providers in order to bridge the gaps between healthcare practices and the needs of multicultural communities.  Diverse Health Hub works directly with a diverse patient and respected provider population in multiple therapeutic areas to promote cultural competence in healthcare. The organization believes access to these diverse perspectives cultivates culturally competent communities.

Related Programs:

ASH 2019: Disparities Around Accessing Health Technology Revealed for a Subset of Myeloma Patients

ASH 2019: Multiple Regimens, Deeper Responses in Multiple Myeloma Treatment

Myeloma Highlights – #ASH16

MYELOMA HIGHLIGHTS FROM ASH CONFERENCE SAN DIEGO 12/2-6/2016

According to Jack Aiello (definitely not medically trained)

PREFACE

This is my 11th year attending ASH (American Society of Hematology) Conference, where 25,000 attendees from all over the world (hematologists/oncologists, lab researchers, oncology nurses, scientists & 300 pharma companies) present the latest research results via both oral presentations (1000) as well as posters (3000) on all blood cancers. This year there were nearly 700 abstracts (>100 clinical) on Myeloma alone, many of which were selected for oral presentation. I’m grateful to the IMF (www.myeloma.org) and their pharma donors for sending me to ASH so that I can learn and share my patient perspective with you.

Rather than attending talks on Biology, I typically focus on the Clinical Trials, which I’m able to understand and are more relevant near-term to patients. Even at that, there are overlapping MM oral sessions as well as 4’x6’ posters without reprints, so it’s always possible that I have not included something of interest to you or made a typo because I can’t read my own writing as detailed powerpoint slides are presented quickly. You might want to view the published abstracts at www.hematology.org and various press releases. [Wherever possible, I’ve listed Day-Abstract#-Lead Investigator after the trial results, e.g. {Mon-675-T. Zimmerman} and clicking on the abstract number will take you to the actual abstract.]

There are other ways to learn more about results from this conference. There are scheduled webinars (MMRF 1/11/17, IMF 1/12/17) which you can listen to live or by replay. You’ll also find some patient blogs (including mine) as well as MM expert video interviews posted on the IMF website (http://ash2016blogs.myeloma.org), Patient Power (www.patientpower.info), and Myeloma Crowd (www.myelomacrowd.org) among others. And all of us in the SF Bay Area should attend the LLS Blood Cancer Conference (which includes updates from ASH) Feb 4, 2017 (Register Now). Dr. Jeff Wolf of UCSF will do a great job presenting the latest information.

Presentations and posters of clinical trial results follow the same format: Background (including hypothesis), Study Objective, Design & Treatment schema, Patient Characteristics & Cohorts, Responses (include high-risk cytogenetics), Toxicity (hematological and non-hematological), Conclusion, and Next Step. Remember, the goal of Phase I (typically handful of patients) is to determine “Maximum Tolerated Dose”; Phase I/II and II (typically 25-75 pts) continues to measure dosage escalation and safety while looking at responses; and finally Phase III (several hundred patients) compares response rates between new and current treatments.

Treatment schedules are defined for stages of Induction, and optionally Transplant, Consolidation, and Maintenance with specified Randomization along the way; dosage amounts and scheduling are provided for each drug along with optimum number of treatment cycles (typically 28 days). Risk stratification correlates various techniques such cytogentics-FISH analysis (e.g. chromosome deletions and translocations) and gene-expression profiling (GEP).

HIGHLIGHTS (e.g. My Takeaways)

1. In Nov 2015, 3 new drugs were approved for Myeloma…Daratumumab, Elotumumab (both mAb’s) and Ixazomib (oral PI). At this ASH, trials were presented that provided results for using these drugs beyond their current FDA-approved indications such as Dara in combinations and Ixa before and after transplant.

2. Speaking of transplants (SCT), there were lots of abstracts on specific SCT usage…some contradictory. For example, one trial showed SCT plus consolidation benefitting MM pts while another trial showed no difference whether being treated with a single SCT, SCT + consolidation, or a tandem SCT.

3. There were 3 new drugs of interest: Nelfinivar, Selinexar and Venetoclax. Most impressive is that they were particularly effective in certain scenarios: Nelfinivar (with Velcade) for Vel-refractory pts; Selinexar alone for t(11;14) pts; and Ventoclax + dex for quad- and penta-refractory pts. Quad means refractory to Rev, Vel, Pom and Cfz, while Penta include Dara.

4. Minimum Residual Disease (MRD) testing is still not ready for prime time, but one doctor googled “Myeloma + MRD” and found 45 abstracts. MRD tests are certainly being added and reported in trials and while there’s good correlation between PFS/OS and MRD, it’s still not being used to determine subsequent treatment. Since MRD has the potential to guide therapy, stop therapy and change therapy, it’s something we patients need to keep on our radar.

5. There were several presentations on Immunotherapies (mAb’s, CAR-T’s and checkpoint inhibitors). However other than mAb’s like Dara, Elo, and Isatuximab (not yet approved), CAR-T and checkpoint inhibitors are still in a very early stage of evaluation.

6. More on checkpoint inhibitors. Dr Don Benson (OSU) explained that MM suppresses the immune system from doing its job. Inhibitors of the KIR ligand and PD1/PDL1 pathways enable NK cells and T-cells respectively to do a better job of finding and destroying MM cells. The concern, however, is that normal cells also have these built in checkpoints and you wouldn’t want the immune system destroying these cells as well. One doctor even mentioned that these are still “scary”.

COMMENTS AND DISCUSSIONS I FOUND PROVOCATIVE

7. “For patients in a CR, half will be MRD- and half will be MRD+.” B. Durie (IMF)

8. “I always see SMM patients again 1 month after diagnosis. It’s more important to know the tempo of their disease than risk factors.” S. Lonial (Emory)

9. “I’m afraid that some might interpret MRD- as a cure, which is not true.” J. Mikhael (Mayo)

10. “Half of SMM patients have MGUS-like disease and half are more like MM. If we only knew which patients were which, we would know who to treat.” S. V. Rajkumar (Mayo)

11. “It’s becoming more difficult to select the best treatment option for R/R MM patients.” P. Moreau (France)

12. When discussing the management of ND HRMM pts, Dr A. Dispenzieri (Mayo) reminded attendees that “high risk” not only includes chromosome abnormalities but also fitness/frailty assessment and access/cost of treatment. Whether TE or nTE, these patients should consider Velcade-based induction and maintenance. TE pts should consider Tandem SCT. And for renal-impaired, Velcade triplet is more effective than a Velcade-doublet.

13. “Although CR and MRD- should be the goal, not all patients get there and this needs to be considered.” N. Raje (UMass)

14. “For relapsed patients, doctors must consider previous treatments and responses. R/R MM pts should consider including POM.” N. Raje (UMass)

15. “Every 5 years, folks ask if SCT is dead. But it isn’t…not yet”. P. McCarthy (Roswell-NY)

16. “Today we are curing a subset of patients. We just don’t know who they are.” S. Lonial (Emory)

SMOLDERING MM

17. n=270 in 2 trials demonstrated that multiparameter flow cytometry may represent a better way (actually a “biomarker”) to classify HR SMM. Specifically this test classified these patients as MGUS-like (17%), Intermediate between MGUS & MM (66%) and MM-like (18%). Then 2-yr median Time-to-Progression (TTP) to MM/risk % was shown to be “not reached”/4%, 57 mos/25%, and 16 mos/58% respectively. {Sun-373-B. Paiva}

18. n=34 Elo (weekly)-Rev-dex in High Risk SMM, where HR is based on cytogenetics t(4:14), t(14:16, 17p- or +1q amplification. ORR was 82% (including CR 9%) and thus far no pts have progressed to active MM during or after protocol therapy. {Mon-976-I. Ghobrial}

FRONTLINE THERAPY FOR TRANSPLANT INELIGIBLE (NTE) PATIENTS

19. Ph 3, n=1600 NDMM pts, final PFS & OS results of the FIRST trial were presented comparing Rd continuous vs Rd 18 mos vs MPT. 4-yr PFS % (33 vs 14 vs 14) and median OS mos (59 vs 62 vs 49) and other factors showed overall benefit for continuous Rd. {Sat-241-T. Facon }

TRANSPLANTS

20. Ph 3, n=1400 NDMM pts, EMN02/HO95 MM trial VCD (R1) VMP or SCT (R2) VRD consolidation or none followed by Rev maintenance till progression, examined the impact of consolidation, which benefitted std but not HR pts. Best news was that 3yr OS from R2 was 86% and 87% respectively.{Sat-242-P. Sonneveld}

21. Additional analysis was provided from the EMN02/HO95 MM trial shown above. Specifically, the SCT arm did show benefit over the VMP arm for all pts, e.g. ORR 86% vs 75% and 3yr PFS 65% vs 57%; for HR pts 3yr PFS was 52% vs 30%. So ultimately HR MM pts benefitted by SCT but not from consolidation (above). {Mon-673-M. Cavo}

22. Ph 3, n=581 Myeloma XI study investigated a response-adapted approach to induction. Specifically if pts achieved less than VGPR to induction (IMID regimen), they would be randomized to be given an additional regimen (PI based) before SCT. The consolidation side improved median PFS from 20 to 30 mos. For those having a transplant, the PFS was even better (31 mos versus 55 mos). However even Transplant Ineligible pts showed PFS benefit with consolidation of 14 vs 20 mos. {Sat-244-G. Jackson}

23. n=42, Ph 2. IxaRd –> SCT -> IxaRd -> Ixa maintenance for NDMM pts. Note this all-oral therapy (except for SCT). VGPR (CR) or better at the end of Induction, SCT and Consolidation were 36% (12%), 78% (38%), and 77% (44%) respectively. Adverse events were well-tolerated with no grade 3/4 neuropathy. If the future Dara may be added to this regimen. {Mon-674-P. Moreau}

24. n=76, Ph 2. KRdx4 -> SCT -> KRdx4 -> KRd maintenance (x10) -> Rev maintenance. Analysis were done after cycles 4, 8, and 18. At C18, ORR was 94% with a very high 86% in CR. [BTW, with no SCT for another group of 53 pts, C18 ORR/CR was 90%/40%.] MRD was done by both Flow and NGS. At C8 and C18 MRD- was 86%/64% and 97%/71% respectively by each method. For HRMM pts, ORR was 96% (81% CR) and C18 MRD- was 90%/63%. And 3yr PFS/OS was 86%/95%. When asked to compare this KRd regimen with the IxaRd regimen results above, the speaker said KRd speeds up response but has higher toxicity. {Mon-675-T. Zimmerman}

25. n = 46, KRdx4 -> SCT -> KRdx4 -> Rev maintenance (nearly the same as above) resulted in similar outcomes sCR = 57%, >= VGPR = 91%, MRD- = 70% with no neuropathy. {Mon-1142-G. Jackson}

26. n=111, Ph 2. KTdx4 -> SCT –> KTd x4 (T lowered from 200mg to 50mg). ORR after consolidation was 95% (CR=64%). Overall 3yr PFS and OS were 68% and 90% respectively. For HR pts, responses and OS were about the same while PFS was less. {Mon-1141-R. Wester}

27. n=750 pts were randomized into 3 arms. Arm 1, denote ACM, received one auto SCT, 4 cycles of RVD consolidation, then Rev maintenance until progression. Arm 2, denoted TAM, received a tandem (two) SCT’s and Rev maintenance until progression. Finally Arm 3, denoted AM, received a single auto SCT, then Rev maintenance until progression. After 38 months, the PFS (57%/56%/52%) and OS (86%/82%/63%) were comparable in all three groups. Furthermore, when looking at subgroups such as High Risk, there was no differences (all about 24% PFS and 75% OS). Even overall secondary primary cancers (SPMs) were all about 5%. {Tue-LBA-1-E. Stadtmauer}

TREATMENTS FOR RELAPSED/REFRACTORY (R/R) PATIENTS

28. MRD results were presented for the recent POLLUX (DaraRd vs Rd) and CASTOR (DaraVd vs Vd) trials, which resulted in FDA approval of using Dara with Rev or Vel. MRD- outcomes were typically about 3x in the Dara arms versus the non-Dara arms. Further, MRD- for Dara-Rd was about 2x compared with the Dara-Vd arm (25% vs 10% evaluated by NGS with 10-5 sensitivity). {Sat-246-H. Avet-loiseau}

29. Another update of the Pollux study (DRd vs Rd) for RRMM pts showed benefits in ORR (94% vs 77%), 18 mos PFS (77% vs 50%), and MRD- (25% vs 6%). ORR for HRMM was 89% vs 67%. {Sun-489-P. Moreau}

30. n=41 RRMM pts on Dara-Pom-dex trial also examined “retreatment” with Dara. ORR 89% for Dara & Pom naïve but nearly 35% ORR for pts refractory to both Dara and Pom {Sun-492-A. Nooka}

TARGETED THERAPY

31. Ph 3, n-432. Tourmaline-MM1 study Ixa-Rd vx Rd for RR MM pts that resulted in Ixazomib approval Nov 2015. This sub-analysis examined patient expression level of c-MYC (proto-oncogene regulation cell proliferation & cell death. High c-MYC expression pts showed a 6 month PFS benefit on the Ixa-Rd over Rd. {Sat- 243-A. Di Bacco}

NEW DRUGS

32. n=34 Nelfinavir is an approved, generic oral drug, and HIV protease inhibitor used to treat AIDS. When combined with Vel-dex (NVd) for Vel-refractory pts (and 76% were also Rev-refractory), ORR = 65% include 5 pts achieving VGPR. {Sun-487-C. Driessen}

33. n=66 (inc 30 pts had t(11;14) MM. Ph 1. Venetoclax, BCL-2 inhibitor, single agent for RRMM showed 21% ORR but 40% ORR for t(11;14) pts (88% if also high BCL-2 expression). {Sun-488-S. Kumar}

34. n=65 Venetoclax + Vel-d for RRMM pts. Overall ORR 67% with best responses ORR=97% for Vel non-refractor and 1-3 prior tx lines. Worst ORR for >6 tx lines (20%) or Velcade-refractory (31%). Likely Ph 3 to be Ven-Vd vs Vd. Higher BCL-2 expression means better ORR. {Mon-975-P. Moreau}

35. n=45, Ph 2 Pembrolizumab (checkpoint inhibitor Keytruda) + Pom-dex for RRMM, all refractory to Rev, 73% double refractory. ORR 65% (inc 27% >= VGPR and median PFS 17 mos. However ASE’s included 40% grade 3 neutropenic and . pts required dose reduction. {Sun-490-A. Badros}

36. n=79 including 48 quad (Rev-Vel-Pom-Cfz) and 31 penta (quad + Dara) refractory. Selinexor (80 mg 2x/wk) (oral XPO1 inhibitor) and dex (20 mg 2x/wk) regimen (Sd) goes by the name STORM study. ORR was about 20% for both quad and penta but also had grade 3/4 hematological events. Median OS was 9.3 mos. {Sun-491-D. Vogl}

37. n=12, Phase 1 study of Selinexor-Cfz-d in RRMM pts. These 12 pts were also refractory to Cfz. ORR for this group was 67% (15% >= VGPR) with 3.7 mos PFS. {Mon-973-A. Jakubowiak}

38. n=22, Ph 1b/2 study of Selinexor (100 mg/wk)-Vel-d (SdB) for RR MM pts, including those refractory to Vel (STOMP trial). Overall ORR=77% (inc 9% CR, 18% VGPR). For Vel-refractory, ORR=67%, while Vel-exposed/naïve had 100% ORR. {Mon-977-N. Bahlis}

39. n=12, Pilot Study of CAR-T CD19 in conjunction with salvage (2nd) SCT for advanced MM. Method: 2 weeks after the SCT, 5 x 107 CAR-T cells are infused. Of these 12 pts, 3 pts had a VGPR and longer PFS than from their first SCT. One patient (featured on the cover of Parade Magazine several months ago) had a 16 mos PFS but then relapsed and is now in a 12-mos CR with Dara. Only one episode of cytokine release for these 12 pts. {Mon-974-A. Garfall}

OTHER RESULTS

40. n=113 For Light Chain MM patients who follow their disease with 24-hr urine analysis (UPEP), the Serum Free Light Chain test offered better correlation with clinical outcomes (e.g. PFS) than urine assessments….and is certainly easier on these patients. {Sun-376-T. Dejoie}

41. There were several presentations on racial disparities. These included {Mon-844-M. Fiala}and {Mon-846-A. Rosenberg}that examined the usage of SCT’s by African American MM pts. The first concluded that when elimininating health disparities and postential access barriers, black pts are will 37% less likely to utilize an SCT. The second focus was on California patients but came up with a similar number 30%. This poster {Sun-3544-S. Ailawadhi}examinedMM complications (CRAB symptoms) among different racial groups with blacks having the highest rate of complications, perhaps being due to reduced access to drugs/supplemental insurance coverage.

42. An interesting study for Myeloma Cast Nephropathy (kidney impairment) comparing Haemodialysis with High Cut-off vs Standard High Flux Dialyzer in pts receiving Velcade-based therapies. With Haemodialysis, 1/2 the pts became dialysis-free versus only 1/3 in the Standard control group. {Mon-978-JP Fermand}

43. n=41 This trial study the efficacy and side effects from administration of Daratumumab via sub-Q injection in R/R MM pts. For pts on the recommended dose of 1800mg given over 30 minutes, the ORR was 41% and Infusion Reaction Rates were lower than with Dara IV infusion. And when asked about pain or bruising at the infusion site, Dr Usmani said that neither were problems. This has the potential to reduce infusion times from six or eight hours to 30 minutes. {Mon-1149-S. Usmani}

SUMMARY

For someone diagnosed with stage III MM 22 years ago with only 2 treatment options available (MP or VAD-SCT) and given 2-3 years expected survival, I’ve seen incredible progress since 2003 when Velcade was first approved. While there continues to be unanswered questions, we now have many more effective treatments for MM, providing patients with better opportunities to manage their disease.

GLOSSARY (according to Jack) Drug (brand names) by Drug Class/Category

IMID – Immunomodulary Drug

T – Thalidomide

R – (Lenalidomide) Revlimid

Pom – Pomalidomide (Pomalyst)

PI – Proteasome Inhibitor

V- Velcade (Bortezomib)

Cfz – Carfilzomib (Kyprolis)

I, Ixa – Ixazomib (Ninlaro)

mAb – Monocloncal Antibody

D, Dara – Daratumumab (Darzalex)

E, Elo – Elotuzumab (Empliciti)

Isa – Isatuximab (SAR650984)

HDAC – histone deacetylase inhibitors

Pano – Panobinostat (Farydak)

Steroids

P – Prednisone

D or d – Dexamethasone

Chemotherapy Drugs

C – Cyclophosphamide (Cytoxan)

M – Melphalan

Treatment Measurements

EFS – Event-free Survival

ORR – Overall response (>=PR)

OS – Overall Survival

PD – Progressive Disease

PFS – Progression-free Survival

PFS2 – PFS + next-line treatment PFS

TTP – Time to Progression

TTR – Time to Respond

Treatment Response

CR – Complete Response: No sign of MM (0 M-spike)

nCR – Near CR (positive M-spike, may be same as VGPR)

MR – Marginal Response: 0-50% reduction in MM

PR- Partial Response: 50% reduction in MM

SD – Stable Disease i.e. no response but also not worse

sCR-Stringent CR: CR+ normal FLC & no clonal cells

VGPR – 90% reduction in MM

MRD – Minimum Residual Disease typically by Flow Cytometry (NGF) or DNA sequencing (NGS) to provide more accurate measure of MM.

Side Effects

AE (ASE) – Adverse Event (Adverse Side Effects)

DVT – Deep Vein Thrombosis (blood clots)

MTD – Maximum Tolerated Dose

ONJ – Osteonecrosis of the Jaw

PE – Pulmonary Embolism

PN – Peripheral Neuropathy

QOL – Quality Of Life

VTE – Venous Thromboembolism (PE + DVT)

Tests/When to treat?

CRAB – High Calcium, Renal, Anemia, and Bone…

CRABi – CRAB + “i” increased infections

FLC – Free Light Chain

SCT – Auto stem cell transplant.

TE, NTE – Transplant Eligible of Not TE

“d” and “D” – Typically both mean Low-dose Dex (40 mg/week) these days

MGUS – Monoclonal Gammopathy of Undetermined Significance

SMM – Smoldering MM

Pt(s) – Patient(s)

n – Number of pts

R/R- Relapsed/Refractory, Ref defined progressing while on Tx or within 60 days.

HR – High Risk

Myeloma Highlights from #ASH15

According to Jack Aiello (definitely not medically trained)

PREFACE

This is my 10th year attending ASH (American Society of Hematology), where 25,000 attendees from all over the world (hematologists/oncologists, lab researchers, oncology nurses, scientists & 300 pharma companies) present the latest research results via both oral presentations (1,000) as well as posters (3,000) on all blood cancers. This year there were nearly 800 abstracts (>100 clinical) on Myeloma alone, many of which were selected for oral presentation. I’m grateful to the IMF (www.myeloma.org) and their pharma donors for sending me to ASH so that I can learn and share my patient perspective with you.

Rather than attending talks on Biology, I typically focus on the Clinical Trials, which I’m able to understand and are more relevant near-term to patients. Even at that, there are overlapping MM oral sessions as well as 4’x6’ posters without reprints, so it’s always possible that I have not included something of interest to you or made a typo because I can’t read my own writing as detailed powerpoint slides are presented quickly. You might want to view the published abstracts at www.hematology.org and various press releases. [Wherever possible, I’ve listed Day-Abstract#-Lead Investigator after the trial results, e.g. {Sat-25-B. Durie} and clicking on the abstract number will take you to the actual abstract.]

There are other ways to learn more about results from this conference. There are scheduled webinars (IMF 1/7/15, MMRF 1/13/15) which you can listen to live or by replay. You’ll also find some patient blogs (including mine) as well as MM expert video interviews posted on the IMF website (www.myelomal.org) and Patient Power (www.patientpower.info) among others. And all of us in the SF Bay Area should attend the LLS Blood Cancer Conference (which includes updates from ASH) Jan 23, 2016 (Register Now). Dr. Jeff Wolf of UCSF will do a great job presenting the latest information.

Presentations and posters of clinical trial results follow the same format: Background (including hypothesis), Study Objective, Design & Treatment schema, Patient Characteristics & Cohorts, Responses (include high-risk cytogenetics), Toxicity (hematological and non-hematological), Conclusion, and Next Step. Remember, the goal of Phase I (typically handful of patients) is to determine “Maximum Tolerated Dose”; Phase I/II and II (typically 25-75 pts) continues to measure dosage escalation and safety while looking at responses; and finally Phase III (several hundred patients) compares response rates between new and current treatments.

Treatment schedules are defined for stages of Induction, and optionally Transplant, Consolidation, and Maintenance with specified Randomization along the way; dosage amounts and scheduling are provided for each drug along with optimum number of treatment cycles (typically 28 days). Risk stratification correlates various techniques such cytogentics-FISH analysis (e.g. chromosome deletions and translocations) and gene-expression profiling (GEP).

 

HIGHLIGHTS (e.g. My Takeaways)

  • In the large French/US study comparing early versus late SCT, the French showed a PFS benefit but not three-yr OS benefit (both arms about 83%), maybe because trial results are not mature. However, the French part of the study only uses one year of maintenance, whereas the US uses maintenance until progression.  The US has yet to report data so will maintenance make a difference to the outcome?  We’ll see.
  • For relapsed patients, treatment isn’t as clear cut but with the recent approvals of Darzalex (Daratumumab), Ninlaro (Ixazomib), and Empliciti (Elotuzumab), patients have more options as they combine each of these with the baseline Rev-dex. How clinicians will use or “sequence” Dara-Rd, Ixa-Rd, and Elo-Rd will likely be better understood over the next one to two years, making it even more beneficial for patients to have a Myeloma expert as part of their treatment team.
  • The Ultra High Risk (plasma% > 60%, FLC ratio > 100, >1 focal lesions) Smoldering multiple myeloma patients (SMM) have already been re-classified as MM pts, even without CRAB criteria. Other SMM pts that have some indication of high-risk features (e.g. perhaps plasma% > 10% and one of FLC ratio > 8 or cytogenetics such as del17p) should investigate participation in a clinical trial such as E3A06 to determine the efficacy of early treatment.
  • Three-drug VRd therapy for newly diagnosed patients has been shown to have longer progression free survival (PFS) and overall survival (OS) than two drugs and should be considered the standard of care. Mayo’s M-SMART (msmart.org) treatment protocol recommendation for newly diagnosed standard and intermediate risk patients has been updated from Rd to VRd (still KRd for high-risk).
  • Minimum Residual Disease (MRD) testing is not ready for prime time, but it has good prognostic value for MM patients, similar to CR being a good prognostic indicator. MRD still needs to be consistently defined using NGS or Flow (8-color/2 tubes). Trade-offs include NGS needs diagnostic sample and has higher cost while Flow needs “fresh” samples. And more trials need to integrate MRD so that clinicians can eventually use MRD results to help guide future treatment plans.  And probably, MRD needs to be combined with PET-CT to get the complete picture.
  • You’ll see reports below that look at survival outcomes such as Progression Free Survival (PFS) and Overall Survival (OS). However, with new treatments available, OS (i.e. death) become less meaningful for a particular drug. Perhaps the assessment of targeted biomarkers will become better measurements of drug efficacy.

 

COMMENTS AND DISCUSSIONS I FOUND PROVOCATIVE

  • We are still trying to determine the role of maintenance. There have been or are currently 242 clinical trials involving maintenance (including “consolidation and “continuous therapy”). Even vaccines (e.g. dendritic cells) are being tested as maintenance. T. Facon (France)
  • Re Using Emerging Therapies up front: “Adding later does not add up.” S. Kumar (Mayo)
  • Re Early Treatment: “In most cancers (lung, breast), early diagnosis and treatment is a prerequisite to OS improvement. When we wait, clones have a chance to develop more aggressive subclones. But we must work to develop predictive biomarkers.” J. San-Miguel (Spain). However, “Should you over-treat 30% of HRSMM pts at the risk of under-treating 70%? What about toxicity? You need more evidence-based medicine.” P. Moreau (France)
  • Flow (NGF) & NGS measure myeloma inside the bone marrow while PET-CT measures myeloma outside the bone marrow. A. Orfao (Spain)
  • I attended an FDA presentation where each FDA MD reviewed their criteria for approving Ixazomib, Daratumumab, and Elotuzumab respectively, citing the specific trial as well as primary and secondary endpoint results. Then Drs. S. V. Rajkumar (Mayo) and P. Richardson (Dana Farber) discussed using these new drugs as front-line and relapsed therapies respectively. Dr. Rajkumar began “Myeloma treatment is moving so fast, the Education Session I gave 2 days ago is already out of date.” To use these drugs front-line, they would be need to be “off-label” and it’s better to use them within a clinical trial for newly diagnosed pts. Dr. Richardson explained the Rd is the “backbone” and we can add V, K, I, D, and E (and SAR in the future?). We’ll understand more about sequencing these combinations in the next 1-2 yrs.

    Convention Hall

    Convention Hall

 

SMOLDERING MM

  • “If it’s smoldering, is there a fire?” S. Lonial (Emory) and “Some pts with SMM really have MGUS and others MM…we just don’t know which ones.” S. V. Rajkumar (Mayo)

 

FRONTLINE THERAPY FOR TRANSPLANT ELIGIBLE PATIENTS

  • Ph 1/2, n=48 NDMM pts, including 30% HR, Panobinostat (10mg) + RVd. ORR after 4 cycles was 94% (CR/nCR 46%…compared with past trials RVd-only CR is 10-20%) and 14 of 26 pts were MRD- before their SCT. ASE Grade 3 nausea 6% and PN 4%. {Sun-187-J. Shah}
  • Ph 3, n=525 NDMM pts, VRd vs Rd. Overall Response Rate ORR (82% versus 72%), CR (16% versus 8%) Progression Free Survival PFS (43 versus 30 mos) and Median Overall Survival OS (75 versus 64 mos) all showed the benefits of triplet therapy over doublet. {Sat-25-B. Durie}
  • Ph 3, n>2000 NDMM pts comparing KCRd with CRd (and CTd). It showed the 4-drug regimen that added Carfilzomib resulted in higher >= VGPR (82% vs 62% vs 55%) and that KCRd had lower (!) hematological suppression than CRd (9% vs 16%). {Sun-189-C Pawlyn, UK}

 

FRONTLINE THERAPY FOR TRANSPLANT INELIGIBLE PATIENTS

  • {FIRST subgroup analysis} n=142 High Risk [del 17p, t(4;14) or t14;16)] NDMM pts randomized to 3 arms: Rd till progression vs Rd 18 cycles vs MPT 12 cycles. In non HR pts, median PFS was 31 mos vs 21 mos vs 25 mos while HR pts were 8/18/15 mos. In non HR, 3yr OS % was 77% vs 71% vs 65% while HR pts were 41/40/47%. So while Rd till progression was the winner overall in the FIRST trial, it did not do so well comparably in High-Risk pts. {Mon-730-H. Avet-Loiseau}
  • Ph 2, n=70 NDMM pts, Ixazomib-Cytoxin-Dex (ICd) randomized to C = 300 or 400 mg all oral therapy. Plus Ixa maintenance. Early ORR results better in C=300 arm (78% vs 75%) and >=VGPR (28% vs 21%). PFS @ 9 mos was 90% but data not yet mature. {Sat-26-M. Dimopoulus}
  • Ph 2, n=40 NDMM pts, “RVd-lite” study Rev = 15mg, days 1-21; Vel = 1.3 mg/m2 once/week; dex = 40 mg/wk for pts <75yo and 20 mg /wk otherwise. After 4 cycles, ORR was 90% (including CR 25%), 2 yr PFS is 68%. {Mon poster-4217-E. O’Donnell}

 

TRANSPLANTS

  • Ph 3, n=389 NDMM pts, SCT vs Cytoxin-Rd followed by RP vs P maintenance. SCT showed improvement in median PFS (43 vs 29 mos) and 4-yr OS (86% vs 73%) Median PFS from the start of maintenance was 38 mos for RP vs 29 mos for R-only but 3-yr OS was similar (83% vs 88%). Of note, at the start of maintenance, MRD- was 48% for the SCT arm vs 28% for CRd, even though CR and VGPR numbers were very close. {Sun-392-F. Gay, Italy}
  • Ph 3, n=700 70 NDMM pts, “Determination” RVd +/- SCT + RVd consolidation + R maintenance. The French side of this study showed benefits in the SCT arm for ORR (88% vs 78%), CR (59% vs 49%), 4-yr PFS (47% vs 35%), and MRD- (80% vs 65%) but no OS difference (83%), which could be due to the short timeframe as well as early crossover to the SCT arm. {Sun-391-M. Attal}
  • Ph 3, n=174 (of 297 enrolled) prior SCT pts. Salvage SCT was defined as a 2nd SCT after relapse > 18 mos from prior SCT. All pts were re-induced with Velcade-Doxorubicin-Dex (PAD) and randomized to either 2nd SCT vs 12 wks Cytoxin with crossover. ORR to re-induction was 79%. 4yr OS was 69% (2nd SCT) vs 61% (crossed over to 2nd SCT) vs 50% (no 2nd SCT), so beneficial to have salvage SCT sooner. {Sun-394-G. Cook, UK}

 

TREATMENTS FOR RELAPSED/REFRACTORY (R/R) PATIENTS

  • {ASPIRE subgroup Analysis} Ph 3, n=100 HR RRMM pts. KRd vs Rd, where High Risk is one of del 17p (>60% of plasma cells), t(4;14) or t(14;16). Median PFS for HR was 23 mos vs 14 mos (compared with std risk 30 mos vs 20 mos). ORR from HR was 79% vs 60% (compared with std risk 91% vs 74%). {Mon-731-H. Avet-Loiseau}
  • {Endeavor subgroup analysis}Ph 3, n=465 RRMM , Kd vs Vd outcomes for 1 and 2+ prior lines of therapy. Median PFS: 1 line 22 vs 10 mos; 2+ lines 15 vs 8 mos. ORR: 1 line 82% vs 66%; 2+ lines 72% vs 60%. This presentation concluded that Kd should be considered in pts who have progressed on Rev maintenance. {Mon-729-P. Moreau}
  • {Eloquent-2} Ph 3, n=646 RRMM pts, Elotuzumab +/- Rd. Elo-Rd showed PFS benefit 4.5 mos (19.4 vs 14.9) with very similar Adverse Events except infusion reaction in 10% pts (of which 63% were in the first infusion). {Sat-28-P. Richardson}
  • Ph 1b, n=98 RRMM pts with at least 2 lines of prior therapy. Dara + Pom-d. 67% of pts refractory for both IMI and PI but Pom-naïve. ORR 71% (nearly same for double-refractory) including 9% CR. PFS @ 6 mos is 66%. ASE’s similar to Pom-d alone other than half of pts had IRR (Infusion Rate Reaction) during the first infusion but only 3% at 2nd {Mon-508-A. Chari}
  • Combination of two Ph 2 trials, n=148 pts, double-refractory to a PI & IMID. Daratumumab alone (!). Dosage 16mg/kg. ORR= 31%; median PFS was 7.4 mos; 1 yr OS 69%. For pts who responded, the OS results were even better: OS for MR/SD pts = 17.5 mos, and not reached for >=PR. 10-18% of pts experienced some hematological ASE’s. {Sat-29-S. Usmani}
  • Ph 2, n=32 RRMM pts. Daratumumab (16mg/kg) + Rd. ORR 81% (compared with Rd ORR 61-66% for similar pts); 63% >= VGPR. PFS @ 12 mos 91% (compared with Rd median PFS 11-15 mos for similar pts) and PFS@18 mos 72%. OS@18 mos 90%. ASE’s similar to Rd-alone other than some infusion reaction, usually only with the first infusion. {Mon-507-T. Plesner, Denmark} Note: Dr. Torben Plesner was the first doctor to treat an MM pt with Dara in 2007.
  • Ph 2, n=152 RRMM pts, 50% prior Velcade treatment, 1-3 prior therapies. Elotuzumab (10 mg/kg) +/- Vd. Benefits in >= VGPR (36% vs 27%), median PFS (10 mos vs 7 mos) while ORR about the same (65% vs 63%). Grade 3/4 AE higher in EVd (71%) than Vd (60%), most of this difference being infections (23% vs 15%). {Mon-510-A. Palumbo}
  • {Endeavor subgroup analysis}Ph 3, n=210 RRMM high-risk pts, Kd vs Vd. PFS benefit ~3 mos (8.8 vs 6 mos); ORR 72% vs 58% (CR 16% vs 4%). 1-2% (3% vs 1%) experience more cardiac issues in the Kd arm. {Sat-30-S. Usmani}
  • {Tourmaline-MM1} Ph 3, n=722 RRMM pts, Ixazomib (4mg days 1, 6, 15) +/- Rd (IRd vs Rd). Note that 70% pts previously had Velcade but were not refractory to Rev or PI. Benefits seen in ORR (78% vs 72%, including CR 12% vs 7% and VGPR 36% vs 32%) and Median PFS (20.6 vs 14.7 mos, including del17 21 mos vs 10 mos). OS data not presented due to lack of maturity. {Mon-727-P. Moreau}
  • A pooled analysis of 3 trials example the usage of Pom-dex in 355 pts with moderate kidney involvement (versus 713 pts with no renal impairment. Similar ORR (30% vs 34%), median PFS (4 mos vs 5 mos) and median OS (11 mos vs 14 mos) as well as Grade 3/4 AEs. {Sun poster-3031-D. Siegel}

 

MAINTENANCE (including CONSOLIDATION)

  • Ph 3, n=1964 pooled analysis examined CR patients who received maintenance or not, and determined a significant 5-yr OS benefit (80% vs 54%) and 5-yr PFS benefit (52% vs 19%) for pts on maintenance. {Sat poster-1974-C. Cerrato}

 

NEW DRUGS

  • Ph 2, n=68 RRMM pts. Carfilzomib +/- Filanesib (ARRY-520), a kinesin spindle protein (KSP) inhibitor. Adding FIL show some benefit: ORR 28% vs 24% and median PFS 9 mos vs 4 mos. {Mon-728-J. Zonder}
  • {Keynote-023} Ph 1, n=17 R/R pts, including 50% refractory to Rev. Pembrolizumab (anti PD-l Antibody) + Rd. Pembro dose confirmed at 200mg. ORR 76% (including 56% for pts Rev-refractory), with 4 of 17 pts VGPR (24%). {Mon-505-J.San Miguel}
  • Ph 2, n=27 RRMM pts, 36% HR, 90% Rev-refractory, 70% refractory to both IMID and PI. Pembrolizumab (anti PD-l Antibody) + Pom-d. ORR 60% (including 55% for double-refractory and 50% HR). Gr3 AEs 10-20% pneumonia/infection. {Mon-506-A. Badros}
  • Selinexor (KPT-330), which enhances the natural cell defenses against cancer, was combined with PI’s Velcade or Carfilzomib and shown to potentially overcome drug resistance {Sunday poster-3048-D. Sullivan}. And when combined with Cfz-dex in a Ph 1 trial for RRMM pts including those refractory to Cfz, >= PR was 75%, although results are still early. {Mon poster-4223-A. Jakubowiak}

ASH 2015

OTHER RESULTS

  • A presentation on Social Media for Hematologists was titled “So You Know How to Treat, But Do You Know How to Tweet?” and discussed the increased usage of Twitter during ASH15 from more than 5K participants, including a number of support group leaders (SGL) in attendance. For a summary of all the SGL tweets, use the hashtag #IMFASH15.
  • I attended a meeting conducted by Takeda on the usage of their new oral PI Ixazomib (Ninlaro). It’s indicated for pts who have had 1 prior treatment and used with Rev-d. It needs to be taken on an empty stomach (1 hr before or 2 hrs after a meal) in order to ensure efficacy. And while the standard dosage is a 4mg capsule, it also comes in 3 mg and 2.3 mg capsules. The name Ninlaro? While in development, the drug was called MLN9708. So Ninlaro comes from Nine (minus the “e”) plus “oral” spelled backwards.
  • I attended a session on Patient-Reported Outcomes (PRO’s) which examine Physical, Mental and Social Health in clinical trials and patient care. PRO data is used by Prescribers, Regulators, and Healthcare Payers. You can learn more about this at healthmeasures.net and www.nihpromis.org.
  • This study examined n=693 SCT pts who had various induction therapies RVd, Rd, Vd, and CVd, specifically at pre-SCT and post-SCT >= VGPR results. Pre-SCT responses were 57%/42%/51%/45% and post-SCT were 65%/63%/65%/58%, all quite close. However, maintenance treatment improved 3-yr PFS to 55% vs 39% for no maintenance. In conclusion, when having an SCT, the choice of induction treatment is less important than maintenance {Sun-396-R. Cornell}
  • MRD was evaluated in the French side of the IFM/DCFI 2009 “Determination” trial. Of n=700 pts, 178 pts were evaluated by NGS after maintenance. For CR pts, 83% were MRD- but 17% were MRD+. {Sat-191-H. Avet-Loiseau}
  • CAR-T therapy for myeloma treatment resulted in several oral presentations. In pre-clinical models, SLAMF7-CAR-T cell therapy was shown to be safe and effective in MM treatment. {Sat-115-S. Danhof}. And a company called Cellectis in France showed that they can use healthy donor T-cells and engineer them for a double KO (both TRAC and SLAMF7) to enhance antitumor activity. {Sat-116-R. Galetto}. And a “Late-Breaking Abstract” highlighted a Ph 1 study of 12 RRMM pts using CAR-T cells engineered as anti-BCMA CARs (CAR-BCMA). The B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells in 60-70% of MM pts. To participate in this NCI trial, pts must have had 3 lines of prior therapy and BCMA expression. Pts were given 3 days of Cytoxin and fludarabine beforehand, but no transplant. All 12 pts achieved at least stable disease (SD) with 1 sCR, 1 VGPR, and 2PR’s, typically better results as dosages increased. Pts incurred substantial toxicity (fever, kidney, cytokine release, and more but these AE’s were all reversible. Still, a follow-up trial eligibility criteria will include pts have less that 50% plasma cells. {Tue-LBA-1-J. Kochenderfer}
  • MRI & PET-CT were evaluated in the French side of the IFM/DCFI 2009 “Determination” trial. At diagnosis for n=134 pts, MRI and PET-CT were positive for 95% and 91% of pts. After 3 cycles of RVd, MRI was still positive in 93% but PET-CT in only 55% and was a better prognostic indicator for PFS but not OS. Before maintenance, MRI was not a good prognostic indicator for PFS or OS but PET-CT results were associated with significant improvement in both PFS and OS. As such, an MRI may not be needed for follow-up, while PET-CT should be part of follow-up. {Sun-395-H. P. Moreau}
  • Ph 2, n=100 pts, 25 per arm. Isatuximimab (SAR650984) single agent at different dose/frequencies: Arm 1: 3mg/kg every other week (q2w); Arm 2: 10mg/kg q2w for 4 doses, then q4w; Arm 3: 10mg/kg q2w; Arm 4: 20mg/kg qw x 4 dose then q2w. ORR: 9%, 20%, 29%, 24%. Gr 3 anemia in 20% of pts. {Mon-509-T. Martin}
  • A Medicare cost study was done for 3000 MM pts that assessed the economic burden for both MM treatment costs and pharmacy antiMM cost PPPM (cost per-patient per-month) for treatment lines First ($14K, $3K). Second ($16K, $3K), and Third ($16K, $3K) in 2015 dollars. Average treatment duration was 8, 6, and 5 mos respectively. {Sat poster-2100-C. Chen}
  • A study examined Cytogenetic (CG) Progression for 130 pts over the course of their disease, taking bone marrow samples and looking for risk factors such as del 17p, t(14;16), t(14;20), t(4;14), del 13 and gain 1q21. 90 (69%) of 130 pts had normal CG at diagnosis but 27% of these pts developed abnormal CG during disease course, resulting in shorter median OS (4 yrs) versus pts with normal CG (11.3 yrs) or even pts with any CG abnormality at diagnosis (7.4 yrs). Bone marrow biopsies/aspirates are important during the course of treatment. {Mon poster-4209-C. Pascal}
  • Palliative Care is a multidisciplinary approach to symptom management, psychosocial support, and assistance in treatment decision-making for both patients with serious illness and their families. Unlike Hospice, PC does not require either a terminal diagnosis or proximity to death.

In the US there are >6500 board-certified palliative medicine physicians and >18,000 certified non-physician palliative care professionals who work together with a patient’s other doctors to provide an extra layer of support. PC in the setting of SCT should be considered from the day of diagnosis and tied to need, not to prognosis. How do we balance the trade off in which life may be prolonged and cancer cured, but quality of life is poor? PC has particular relevance in oncology given recent studies which link PC to improved patient QOL, improved survival, and decreased cost of care.

 

SUMMARY

For someone diagnosed with stage III MM 21 years ago with only 2 treatment options available (MP or VAD-SCT) and given 2-3 years expected survival, I’ve seen incredible progress since 2000, and especially this past year 2015. While there continue to be unanswered questions, we now have many more effective treatments for MM, providing patients with better opportunities to manage their disease.

GLOSSARY (according to Jack)

Drug Class/Category

IMID – Immunomodulary Drug

PI – Proteasome Inhibitor

mAb – Monocloncal Antibody

Drugs (Brand Name)

C – Cyclophosphamide (Cytoxan)

Cfz – Carfilzomib (Kyprolis)

D – Daratumumab (Darzalex)

E – Elotuzumab (Empliciti)

I – Ixazomib (Ninlaro)

M – Melphalan

P – Prednisone

Pano – Panobinostat (Farydak)

Pom – Pomalidomide (Pomalyst)

R – (Lenalidomide) Revlimid

S – Isatuximab (SAR650984)

T – Thalidomide

V- Velcade (Bortezomib)

Treatment Success Measurements

EFS – Event-free Survival

ORR – Overall response (>=PR)

OS – Overall Survival

PD – Progressive Disease

PFS – Progression-free Survival

PFS2 – PFS + next-line treatment PFS

TTP – Time to Progression

TTR – Time to Respond

Treatment Response

CR – Complete Response: No sign of MM (0 M-spike)

nCR – Near CR (positive M-spike, may be same as VGPR)

MR – Marginal Response: 0-50% reduction in MM

PR- Partial Response: 50% reduction in MM

SD – Stable Disease i.e. no response but also not worse

sCR-Stringent CR: CR+ normal FLC & no clonal cells

VGPR – 90% reduction in MM

MRD – Minimum Residual Disease typically by Flow Cytometry (NGF) or DNA sequencing (NGS) to provide more accurate measure of MM.

Side Effects

AE (ASE) – Adverse Event (Adverse Side Effects)

DVT – Deep Vein Thrombosis (blood clots)

MTD – Maximum Tolerated Dose

ONJ – Osteonecrosis of the Jaw

PE – Pulmonary Embolism

PN – Peripheral Neuropathy

QOL – Quality Of Life

VTE – Venous Thromboembolism (PE + DVT)

Tests/When to treat?

CRAB – High Calcium, Renal, Anemia, and Bone…

CRABi – CRAB + “i” increased infections

FLC – Free Light Chain

SCT – Auto stem cell transplant.

“d” and “D” – Typically both mean Low-dose Dex (40 mg/week) these days

MGUS – Monoclonal Gammopathy of Undetermined Significance

SMM – Smoldering MM

Pt(s) – Patient(s)

R/R- Relapsed/Refractory Ref defined progressing while on Tx or within 60 days.

 

 

ASH 2015 Annual Meeting

ASH 2015

The American Society of Hematology Annual Meeting will take place in Orlando, Florida from December 5 – 8, 2015. PEN will be covering this meeting with expert interviews and round table discussions with expert physicians and patient advocates. Please check back here for details. Thank you!

Tag Archive for: American Society of Hematology

Coming Soon

Please check back soon as we work to build more resources.