Tag Archive for: progression-free survival

How Has CAR T-Cell Therapy Transformed Myeloma Care?

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How Has CAR T-Cell Therapy Transformed Myeloma Care? from Patient Empowerment Network on Vimeo.

How has the emergence of CAR T-cell therapy impacted myeloma care? Expert Dr. Shambavi Richard explains which myeloma patient groups could benefit from CAR T-cell therapy and shares research updates from recent clinical studies. 

Dr. Shambavi Richard is Co-Lead Physician for the Myeloma CAR-T Programs at Mount Sinai Tisch Cancer Center. Learn more about Dr. Richard.

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 What Are the Steps In the CAR T-Cell Therapy Process?

What Are the Steps In the CAR T-Cell Therapy Process?

Transcript:

Katherine:

Dr. Richard, how is CAR T-cell therapy impacting the landscape of myeloma care? 

Dr. Richard:

So, as I’d hinted or alluded to previously, prior to CAR T cells appearing on the horizon, we had very limited options for patients who had had the first several lines of therapy.  

So, once they had been exposed to two proteasome inhibitors, two iMiDs, and then anti-CD38 antibody which is the three major class of myeloma drugs, they are then called triple class exposed or penta-exposed depending on how many of these drugs they’ve been exposed to.   

We had a study called the MAMMOTH study back – this was published back in 2019 prior to the era of CAR T cells and other T-cell directed therapies. And at the time they had looked at patients who were triple class exposed, and who had been exposed to daratumumab were refractory to daratumumab as their last line of therapy. And what we saw was with their next line of therapy or whatever else was available at the time for patients such as these, their expected response rate was only about 30 percent or so, number one.  

Two, their outlook was very poor with a median progression-free survival which means that the amount of time that patients could go without the disease coming back, and that median progression-free survival was less than six months. And their expected even median overall survival was well under a year. So, that was what the landscape looked like when CAR T cells came onto the scene. For instance, the CART2 trials, which is one of the approved products which is cilta-cel which is what we have now, we actually saw for this same group of patients, the response rate was now 98 percent.  

Deep responses were 83 percent. And we now have the final readout of their median progression-free survival which is almost three years. So, you can see a significant difference.  

Under six months, media progression-free survival to three years. And over 50 percent of the patients were living over three years. So, that’s kind of where we are at. I mean so it was no small improvement. This considerably kind of almost reset the bar and has given a new lease of hope and life to patients who had advance myeloma. And one of the things we say in myeloma is although we don’t, as yet, say that myeloma’s curable, we are working towards that. But we are also giving options for other treatments, other research to be effective in patients just by keeping them around longer.  

Katherine:

Have there been any recent research developments involving CAR T-cell therapy that patients should know about? 

Dr. Richard:

Absolutely. So, much as I have highlighted all the hope and the optimism and the good things about this, the fact is we’re still not curing people with these therapies.  

So, we called this a plateau in the survival curve which means that if we achieve that plateau, that means the disease is probably not coming back, and we have essentially the definition of cured. But we’re not seeing that. We’re still seeing a downslope in the survival curves of myeloma which means that patients are still relapsing in spite of these excellent therapies.

So, there’s a lot of research going on into why are patients still relapsing? Is it because they’re losing the antigen which the CAR T cells are recognizing? Is it because the CAR T cells are no longer effective even though the antigen is still present? Is it because there’s a considerable lag time between the patients being freezed or collected, the cells being collected for the genetic modification in the lab to the time when the patients can actually receive these cells? And that can be anywhere between four to eight weeks.  

So, during this time period, patients with advanced myeloma may not remain static with their disease. The disease is progressing. They’re getting worse. They may not be candidates for these kinds of therapies. So, one of the areas of research is how can we speed up this process, this manufacture process? How can we make it much more available? Because they’re limited by the manufacturing facilities, their abilities to have these viral vectors, to be able to transduce these cells and genetically modify.

So, can we take them off of those kinds of things? Can we automate this? Can we improve these manufacturing platforms? So, a lot of different things are being tested. And then as I’d also mentioned earlier, right now they’re approved for advance myeloma, but what if we can bring them up earlier? Are patients actually going to get cured by that? Are they going to have a much better progression-free survival with that versus waiting until they’re very advanced? So, these are all many, many things that are being looked at.   

In addition, a lot of these CAR T products, these approved products, all them are all recognizing one antigen on the myeloma cell. Now there are products are being looked at that are dual target antigen recognition ability. So, that’s another thing. So, maybe if the CAR T cells are missing one of the antigens, and they’re not able to use that to kill the myeloma cell, maybe the other antigen can pick up the slack. So, these are various things that are being looked at. 

Small Cell Lung Cancer and Immuno-Oncology | What Patients Need to Know

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Small Cell Lung Cancer and Immuno-Oncology | What Patients Need to Know from Patient Empowerment Network on Vimeo.

What do immuno-oncology advancements mean for limited stage and extensive stage small cell lung cancer (SCLC)? Dr. Rafael Santana-Davila with the University of Washington School of Medicine explains the research advancements in immuno-oncology and the status of these treatments and clinical trials for LS-SCLC and ES-SCLC patients.

[ACT]IVATION TIP

“…patients who are diagnosed with small cell lung cancer should ask a doctor, ‘What about immunotherapy? Is that the right thing for me?’”

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Transcript:

Lisa Hatfield:

Could you please explain research advancements in immuno-oncology and what this means for limited and extensive stage small cell lung cancer patients? And which patients have access to that?

Rafael Santana-Davila:

So, immuno-oncology is something that has completely changed the paradigm of treatment of patients with cancer, and very rough explanation, very simple is treatment that augments a patient’s own immune system so the immune system can recognize the cancer. This has changed dramatically how we, treat many cancers and many cancers, or sorry, many patients, when this is successful, can have very long survivals thanks to development of immunotherapy.

So, a few years ago, there were clinical trials that showed that the addition of PD-L1 inhibitors, which are a type of immunotherapy added to chemotherapy can both extend the duration of what we call progression-free survival, which is the amount of time before the cancer grows, as well as overall survival, which is obviously how long a patient lives.

But the addition of these medications can extend both of these numbers and is helping patients live longer. This was an extensive stage. So today there are two drugs that are approved by the FDA to add to the addition of chemotherapy. There are atezolizumab (Tecentriq), and durvalumab (Imfinzi). They are, in our eyes, equal.  One is not better than the other. And they are added to chemotherapy. Chemotherapy is continued for, in the majority of cases, for four cycles, and then patients go on to receive immunotherapy by itself. This is an extensive stage lung cancer. A limited stage lung cancer, there are current clinical trials that are asking the question of whether these medications are also worth it, do they improve things?

We do not know the answer to that question as of today. We are also very hopeful that they do, but we’re waiting for the results of those clinical trials. So which patients have access to it today is those patients that have extensive stage disease and that is the standard of care. So an activation tip for this is patients who are diagnosed with small cell lung cancer should ask a doctor, “What about immunotherapy? Is that the right thing for me?”

And in the great majority of extensive stage disease, they will be eligible for unless there are contraindications. Some very main contraindications is a history of autoimmune diseases or patients that are in immunosuppressive drugs, but that is a minority of patients.

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Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma

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Expert Perspective: Advances in Treating Relapsed and Refractory Myeloma from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan, of Ohio State University Comprehensive Cancer Center – The James, reviews currently available treatments as well as those in development for patients with relapsed or refractory myeloma. 

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

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Transcript:

Katherine:

Are there any recent advances in treatment for patients with relapsed or refractory disease?  

Dr. Khan:

Currently and in the past 20 years or so, we’ve seen about 20 approvals for new drugs for patients with multiple myeloma. The way the approval process works it typically looks at the effectiveness of a drug in the relapsed refractory setting first. And after establishing the safety and efficacy, the therapies are moved earlier in the disease course.   

The great example of this are the anti-CD38 monoclonal antibodies daratumumab and isatuximab. They were first approved in the relapsed refractory setting in combination with other antimyeloma treatments. And due to their impressive effectiveness and relative safety, they’re already being used in the frontline setting for patients with newly diagnosed multiple myeloma.   

In the newly diagnosed setting, a commonly cited study is the phase two GRIFFIN trial. And that added daratumumab to the BRd, or bendamustine (Bendeka, Treanda), lenalidomide (Revlimid), dexamethasone backbone.  

And Europe, they completed the phase three study of adding isatuximab, the other anti-CD38 monoclonal antibody to the BRd backbone. And what we’re finding what was very effective in the relapsed refractory setting was actually adding to the efficacy of newly diagnosed treatment regiments. As a side note, these trials – there are also trials looking at daratumumab and isatuximab in the smoldering myeloma phase, so moving it even earlier.  

I think one of the most attractive new targets in myeloma is targeting this antigen called B-cell maturing antigen, and a number of therapies are being developed or are already developed for it. The first approved was belantamab mafodotin, and this is an antibody drug conjugate. 

So, when the antibody binds to BCMA on the multiple myeloma cells, it releases its toxic payload into the myeloma cell. And so, it’s very effective towards myeloma, and no other good cells or fewer other good cells are affected by it. To provide some numbers, in patients with a median of seven prior lines of treatments, meaning their myeloma had relapsed that many times, the response rate was about 30 percent. And a fifth of those patients had VGPR, very good partial response, or better response.  

There are also bispecific antibodies that target this myeloma marker, and we anticipate getting one approved soon in the U.S. called teclistamab. Teclistamab is an antibody that binds both CD3 on T cells of the immune system and B-cell maturating BCMA on the myeloma cells. 

So, the way this antibody kills myeloma is by activating the T cells, the immune system, and directly killing the tumor. So, this was recently published in the New England Journal of Medicine. And in people who were treated with at least five prior lines of therapy, the response rate was about 63 percent, and the median progression-free survival, or the time until the myeloma progressed, was about 11 months.  

We were very active in a clinical trial looking at the effectiveness of another antibody, a bispecific antibody, called Regeneron 5458. In a similar patient population, the response rates were 75 percent in the higher-dose level group, and right now it’s actually a bit too early to tell how long the progression free survival is or the duration of response. 

There are also other bispecifics in development targeting other myeloma markers ssuch as talquetamab, that binds to a marker called GPRC5D, and cevostamab, which binds to a marker called FcRH5. The response rates as single agents in patients with relapsed refractory multiple myeloma are 66 percent and 45 percent respectively. These are all incredible numbers for a single drug in the relapsed refractory setting.  

How Is CAR T-Cell Therapy Changing Myeloma Care?

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How Is CAR T-Cell Therapy Changing Myeloma Care? from Patient Empowerment Network on Vimeo.

Dr. Abdullah Khan discusses how CAR T-cell therapy works to treat myeloma, the currently approved CAR T-cell therapies, and the outcomes related to progression free survival (PFS) for patients with heavily pre-treated myeloma.

Dr. Abdullah Khan is a hematologist specializing in multiple myeloma and plasma cell disorders at the Ohio State University Comprehensive Cancer Center – The James. Dr. Khan is also an assistant professor in the Division of Hematology at The Ohio State University. Learn more about Dr. Khan.

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Transcript:

Katherine:

Let’s talk about CAR T-cell therapy. How is CAR T-cell therapy changing the field?  

Dr. Khan:

Myeloma was a little late to the CAR-T game, but we’re very happy it’s here. The two products approved in myeloma are idecabtagene vicleucel, ide-cel for short, and ciltacabtagene autoleucel, or cilta-cel for short. 

So, the way CAR Ts work, they are customized T cells for each individual patient. You collect the T cell from the patient with myeloma. You reengineer them in the laboratory to produce proteins on their surface called chimeric antigen receptor. That’s CAR portion of the CAR T therapy. And these CARs recognize and bind specific proteins on the surface of multiple myeloma.  

So, these genetically modified T cells are then expanded or multiplied to make millions of cells. They’re sent back to the hospital where they were collected, where the patient is. And they’re infused back into the patient. The hope is that these modified cells, these CAR T cells, will continue to multiply in the patient. And with guidance from that engineered receptor, they will recognize and kill multiple myeloma very effectively. 

So, I can provide some numbers to the outcomes of the two approved CAR T cells – CAR T products in multiple myeloma. The first approved was ide-cel in patients with a median of six prior lines of therapy, a single dose of CAR T was able to produce an objective response rate – that’s how many people responded to the treatment – of 73 percent, and the median, the middle person, progressed after 8.8 months of getting this treatment. The other product, cilta-cel, was also studied in patients with a median of six prior lines of therapy, and the objective response rate was an astounding 98 percent.  

Katherine:

Wow.  

Dr. Khan:

And the median progression-free survival is actually not yet reached. So, these are remarkable results with heavily pre-treated myeloma. And the myeloma community’s very excited to actually bring these treatments to earlier lines of therapy such as a newly diagnosed patient with multiple myeloma. 

Myeloma Research | CAR-T Cell & Bispecifics Study Updates

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Myeloma Research | CAR-T Cell & Bispecifics Study Updates from Patient Empowerment Network on Vimeo.

Myeloma expert Dr. Joshua Richter reviews the latest updates in myeloma research from the 2022 American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) Congress.

Dr. Joshua Richter is director of Multiple Myeloma at the Blavatnik Family – Chelsea Medical Center at Mount Sinai. He also serves as Assistant Professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology. Learn more about Dr. Richter, here.

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

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

Transcript:

Katherine:

There were two major cancer meetings recently, ASCO and EHA. Are there research updates from those meetings that myeloma patients should know about?

Dr. Richter:

Absolutely. These are some of the biggest meetings that we have every year that attract all types of people, patients, caregivers, physicians, nurses, Pharma, even investors from all over the world. We’re coming off of the back-to-back American Society of Clinical Oncology and European Hematology Association meetings, and there were a couple of really important updates and data. One of them at ASCO actually had what we call a plenary session.

A plenary is the top type of session at any one of these congresses, and it was around something called the DETERMINATION trial which looked at something a lot of patients may be familiar with, the notion of getting VRd, Velcade, Revlimid, and dexamethasone, with or without getting a stem cell transplant as part of their initial treatment. Now, many years ago when our initial therapy was not so good, we showed that transplant was better than what was good 30 years ago.

But, we have better treatments now. So, do we still need high-dose chemotherapy and stem cell transplant?

And what was really interesting about this data set is that if you do get a transplant upfront, you do seem to have a longer PFS, progression-free survival, meaning you stay in remission longer if you get your transplant as part of your initial therapy. However, there was no difference in overall survival, meaning how long you actually lived. And this may not make a lot of sense at first, but think about patient one who stays in remission longer, but because now their disease is a little more refractory, the subsequent therapies don’t work as well as compared to the person who doesn’t get the transplant upfront.

And then those latter therapies work a little better, and when you add them all up, they come out about the same. So, I think one of the things that comes out of this is, “Do I need the transplant?” No, you don’t need the transplant as part of your initial therapy.

We’re still trying to figure out who really needs it and who doesn’t, but you can always never do it or save it for a later time. So, that was really one of the big things that came out of the ASCO meeting.

Katherine:

What about EHA?

Dr. Richter:

So, EHA had a lot of updates both in terms of CAR T-cell therapies and bispecific antibodies, and bispecific antibodies are near and dear to my heart. They’re my big passion in myeloma, and I had the honor of presenting updated data on the Regeneron 5458 bispecific antibody at EHA.

This is a BCMA CD3 bispecific. So, many people may be familiar with monoclonal antibodies like daratumumab, which is just an antibody that gets injected and attacks the cancer.

Bispecifics are molecules that are injected that have two arms. One grabs onto the cancer cell; the other grabs onto your own immune cells that we call T cells and activates them to attack the cancer. Very interesting new therapy.

Very exciting, and very high response rates in people who have had tons and tons of treatment. So, in people that have seen almost everything in the highest dosing group of the study, 75 percent of people responded, which is very, very high.

But more notably, the big side effect we look out for called CRS or cytokine release syndrome, that’s where we activate your T cells and they get so activated they can cause other problems. That can be pretty high in some of our immune therapies, but in this drug, there’s only 38 percent, and all of this was relatively minor. It wasn’t the really big stuff.

So, the reason why this is so near and dear to my heart is that some of these therapies like CAR T have to be given in a major center that does transplants.

But bispecific antibodies, if put together the right way, can be given in your local hematologist’s, oncologist’s office. So, a lot of great potential long-term get everybody treated with these drugs. And then, one or two other little things that I thought were really huge, one was the combining of bispecific antibodies. Studies called the TRIM protocols combined two different bispecific antibodies, one called teclistamab, and one called told talquetamab. Each got combined with daratumumab.

So, not only are we already seeing just the bispecific by itself, we’re starting to combine it and seeing unbelievable response rates. That was updated at EHA, which was groundbreaking. And then in CAR Ts, two things really caught my mind. One was the CARTITUDE-2 data basically giving CAR Ts earlier on to patients had a 100 percent response rate. Can’t really do better than 100 percent. So, it’s not just about getting 100 percent of people in remission.

It’s keeping them there and curing them, and it starts by getting 100 percent of people to respond. So, really looking forward to see how this develops.

But one of the other things was another CAR T that’s coming out of China that targets two different things. It targets BCMA and CD19, both of which can be found on myeloma cells, although CD19 is actually on the myeloma stem cell. It’s a little kooky. But one of the big issues with CAR Ts is manufacturing time. Right now, it takes four to eight weeks to make them. But in this construct, they were able to make them, it took them between 22 and 36 hours. So, for many people, they were able to manufacture the CAR Ts, theoretically, for patients within one day.

So, if we can not only get this therapy to work but shrink the manufacturing from a month or two to a day or two, that would make this more accessible to more patients, get them to their treatment on time. So, the sky’s the limit with our immune options right now.

Katherine:

What makes you hopeful? 

Dr. Richter:

So, we’ve had what we call Gestalt switches in myeloma. And what I mean by that is let’s rewind decades ago. We gave chemotherapy. Chemotherapy was designed to kill any cell that divides rapidly because that’s what cancer cells like to do.  

It kills the good and the bad. It makes your hair fall out, throw up, horrible stuff. It doesn’t work too well. Then about 20 years ago, we started this switch to the novel therapies, Revlimid, thalidomide, Velcade, and then a decade later, daratumumab. And now, we’re having targeted agents which spend more time targeting the bad stuff, less time doing off-target stuff, really ramping things up.  

We are at the precipice of a brand-new Gestalt switch in myeloma. The immune world. The immune therapies. And right now, T-cell redirection therapy is what we call it either with CAR-Ts, where we take your T cells out, engineer them, and put them back into your body all revved up, or we give you an off-the-shelf, bispecific that grabs onto your cancer and your T cell and, brace yourself, we even have trispecifics, which can engage your myeloma, another cell in your body, and yet another cell.  

If you go on clinicaltrials.gov, which lists all the trials for everything, every disease, there are over 3,000 active trials in myeloma.  

And what I tell people is when I first started and I sat across from a patient, I would say, “I’m really sorry. It’s not curable.” And now I say, “We are curing some people today by accident.” But over the next period of time, we’re going to do this deliberately and more frequently. And the goal is and always has been 100 percent of cure for 100 percent of patients, 100 percent of the time.  

And, I kind of feel right now we’re almost like that 2001: A Space Odyssey when the obelisk lands. We have these immune therapies. We know they’re great. How do we combine them? How do we use them? How do we take all these great tools and turn it into a cure for everyone?”   

And with so many great partners between advocacy groups and pharma and patients and cancer centers, we’re going to collaborate, and we’re going to start getting those answers in my lifetime, and I could not be more excited about that.   

Katherine:

Oh, I bet. I bet. 

Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings

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Myeloma Treatment & Research Updates From 2022 ASCO and EHA Meetings from Patient Empowerment Network on Vimeo.

Myeloma specialist and researcher Dr. Krina Patel discusses highlights from the recent American Society of Clinical Oncology (ASCO) annual meeting and the European Hematology Association (EHA) 2022 Congress. Dr. Patel shares promising research updates related to approaches including: stem cell transplant, CAR T-cell therapy, and bispecifics.

Dr. Krina Patel is an Associate Professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center in Houston, Texas. Dr. Patel is involved in research and cares for patients with multiple myeloma. Learn more about Dr. Patel, here.

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Transcript:

Katherine:   

Dr. Patel, cancer researchers recently came together at the annual ASCO and EHA meetings. Are there any highlights from the meetings that myeloma patients should know about?

Dr. Patel:    

Yeah, so we had some amazing trials that were presented at both. And I got to actually go to Chicago for the ASCO meeting, and I’ll say we actually had a plenary session that was presented for myeloma. That doesn’t happen as often as we like. So, basically that was a study presented by Dana-Farber and all of the different groups around the U.S. that did a transplant study. And basically, they’re looking at patients who got induction therapy when they’re newly diagnosed with transplant versus they didn’t get transplant upfront. And it’s called the DETERMINATION study, and it was to determine should everybody be getting a stem cell transplant.

Katherine:  

Right.

Dr. Patel:   

And this is a trial that’s been going on for over 10 years; that’s why it was so highly anticipated. And basically, the biggest thing that we saw was what we call progression-free survival; so, the time that the myeloma hibernates is what I call it, for PFS. Basically, patients who got transplant upfront, it was 21 months longer that it stayed hibernating than if you didn’t get transplant upfront. So, that’s the trial, that’s what it was looking at, and that’s all they could really say about it. The good news is, even patients who didn’t get transplant upfront but then got transplant in second remission tended to have a really good, long progression-free survival or hibernation in that second remission.

So, it still tells us that right now, a transplant is still important for the majority of our myeloma patients. And basically, that’s sort of what that trial showed.

Now, the difference is we do different types of upfront therapies, and we have new things like CAR T and bispecifics that are coming up earlier. So, we’ll see in the future if it still holds up. But as of right now, it still holds up for transplant. The other big studies, of course, were some of our bispecific studies that use different antigens. So, antigens are the flags that are on the myeloma that we make these receptors for CAR T, so they can find the myeloma, or bispecifics go after that.

And basically, there are other antigens. BCMA, B-cell maturation antigen, is the big one that we use for everything right now. But now, we found even more antigens, which is fantastic.

So, we have something called FcHR5. We have something called GPRC5D. It’s like alphabet number soup, basically. But what’s really exciting is that these new antigens give us a different way of getting to that myeloma, especially if someone has already had a BCMA therapy and they’ve relapsed on that. Well, now we have even new ways to get to that myeloma cell. So, I think that’s some really, really exciting data.

And then, I’ll say the other big one was one of the CAR Ts, Cilta-Cel was something that they presented.

Again, this was two years after the last patient had gotten treated on the trial. And so far, they still have about 71 percent of patients that are still in remission two years after. So, that is huge.

Katherine:                  

Wow.

Dr. Patel:  

We’ve never seen that in relapsed refractory patients before, so we’re really, really excited to kind of have gotten that data to say, “Okay, we found a brand-new way of treating myeloma.” And it really is changing how we’re looking at even earlier lines of therapy now.

Katherine:   

Such promising news. That’s great.

Confusing CLL Terms Defined

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Confusing CLL Terms Defined from Patient Empowerment Network on Vimeo.

What is FISH testing? What is IGHV? Physician assistant Danielle Roberts explains the meaning of these often confusing terms and their role in disease monitoring and CLL treatment decisions.

Danielle Roberts is a physician assistant with the Bone Marrow Stem Cell Transplant (BMT) team at Winship Cancer Institute at Emory University. Learn more here.

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Transcript:

Danielle Roberts:    

So, a FISH test is a test from your either blood in your bloodstream or from your bone marrow biopsy. And it stands for florescence in situ hybridization. And this is a highly specific test that looks at the chromosomal changes with CLL. This can be done in the peripheral blood or in the bone marrow.

And it’s important to remember that when we consider genetic testing and CLL, we aren’t talking about inherited genes, but the abnormalities that occur within the CLL itself.

So, an IGHV test is a mutational test that stands for the immunoglobulin heavy-chain variable gene locus. This can also be done in the peripheral blood and the bone marrow biopsy. This test can help us determine treatment options as well as help with determining what high-risk features there are for your particular disease.

So, 17p deletion is the deletion of the long arm of chromosome 17. This can be seen at initial diagnosis or it can be acquired later on in disease progression. So, for all patients this is one of the more important tests that if you’re going to ask your doctor if you’ve had, you should ask at a diagnosis. If you’ve relapsed later on, you should ask again if that mutational status is being observed or checked in your follow-up testing.

17p deletion is something that can be acquired along the course of your disease progression. It is not always seen at initial diagnosis but can be acquired if you are relapsed or refractory. Therefore I recommend that every time you’re having peripheral blood for flow or if you’re having bone marrow biopsies, especially if it’s for treatment planning purposes, you should advocate to your physician team to make sure that this test is being performed as it will drive – or as it can drive treatment decision-making.

Practical Advice for Coping with a CLL Diagnosis: What’s Next?

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Practical Advice for Coping with a CLL Diagnosis: What’s Next? from Patient Empowerment Network on Vimeo.

After receiving a diagnosis of chronic lymphocytic leukemia (CLL), patients can have a variety of concerns. Physician assistant Danielle Roberts shares her top three pieces of practical advice for patients to move forward. 

Danielle Roberts is a physician assistant with the Bone Marrow Stem Cell Transplant (BMT) team at Winship Cancer Institute at Emory University. Learn more here.

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Transcript:

Danielle Roberts:       

My recommendations if I could have three things that I would recommend all patients with CLL do, 1.) It would be to have your financial information kind of in line or know how to find that. Unfortunately, a lot of the medications that we use to treat disease are incredibly expensive. However, there are really good patient assistance programs out there. In order to be able to apply for patient assistance programs you do have to submit your financial information to them. So, I would really suggest that you have access or be able to know where to find that.

I would also really recommend you talk to your family members in so that they understand what’s – where you are with your treatment and what’s going on. As a physician’s assistant, one of the questions I generally get is when they bring in a family member or somebody who has not been along in their journey for their treatment, if they’re asking lots of questions, that was and kind of diagnosis. So, I encourage people to talk about that at the beginning, so everybody understands where they are and what the plan for the future is going to be.

And then the last thing that I always recommend to everybody is to understand that not one treatment is right for everybody. Understand that things are going to change and we’re all going to grow and we’re going to learn with the process. But if you don’t tell your healthcare team what’s going on, we can’t help you. And we say that there is no such thing as a bad question to us. You’re never bothering us. That’s what we’re here for. Rather you tell us, even if it may be something you feel is minor, ahead of time so that we can address it and work towards a solution, if there needs to be one.

How Could Emerging CLL Treatments Impact Your Care?

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How Could Emerging CLL Treatments Impact Your Care? from Patient Empowerment Network on Vimeo.

In the changing world of chronic lymphocytic leukemia (CLL) research, how can emerging treatments impact care for patients? Dr. Jennifer Woyach shares information about targeted therapies, immunotherapy and clinical trials, and explains why she is hopeful about the future of CLL care.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

That’s a good point. Are there emerging treatments patients should know about?

Dr. Woyach:               

Yeah. There are a lot of really exciting things going on in CLL right now. And CLL is a disease that has been completely transformed in the last five to 10 years and is poised to do so again. So, I mentioned these therapies that we use for frontline treatment, and there are clinical trials now combining them together. So, these agents work so well on their own. Are they going to be even better if we add them together?

There are also newer target therapies, different targets that we are finding increasingly important in CLL, as well as a modality called CAR-T cells, which most people have heard of where we take patients’ own T cells, modify them in the lab and then, give them back with a goal of getting those cells engineered to kill CLL cells.

These are all things that are not ready for prime time in CLL yet but are available in clinical trials. And I think one other thing I’d really like to put a plug in for is clinical trials in CLL, because right now we’re at a point where our therapies are really very good. But if people just do those treatments, we are never going to figure out which one is the best or figure out, for specific types of patients, which treatment is the best. And so, I advocate that any of my patients that are eligible for clinical trials should consider them, because that’s how we make progress in the disease from an altruistic sense.

That’s how we make things better for everybody. That’s one way a patient can think about it. But more personally than that, being in a clinical trial gives somebody the opportunity to get a treatment that they otherwise wouldn’t get that might be better than our standard of care therapies.

Katherine:                  

Dr. Woyach, as a researcher in the field, why are you hopeful?

Dr. Woyach:               

I am so hopeful in CLL because there is so much that we’re learning every day about the biology of the disease, about specific mutations and other genetic factors that are important and really can be targeted by new drugs. Paralleling our understanding of the disease, there also are many more techniques to make these targeted therapies that kill cancer cells selectively while sparing normal cells and making our drugs even more tolerable.

And I think both the targeted therapies like this and the potential of combining them, figuring out sequences that are best but then, also these newer modalities where we, actually, get the immune system involved like the CAR-T cells. They’re making CAR NK cells now. And just lots of other strategies that could be used together with targeted therapies to, hopefully, cure the disease.

Targeted CLL Therapy: What Are the Side Effects?

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Targeted CLL Therapy: What Are the Side Effects? from Patient Empowerment Network on Vimeo.

What are common side effects of chronic lymphocytic leukemia (CLL) targeted therapies? Dr. Jennifer Woyach discusses side effects of specific targeted therapies and the importance of reporting any issues to your doctor for optimal quality of life.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

If there are side effects, what would some of the side effects be for these targeted therapies?

Dr. Woyach:               

So, it depends on the drug. So, BTK inhibitors, specifically, ibrutinib can cause some joint and muscle pain, some rashes, diarrhea, heartburn. Those are things that tend to, if they’re going to happen, usually happen earlier on in treatment and tend to get better over time. It can also cause high blood pressure. It can cause an abnormal heart rhythm called atrial fibrillation.

So, those are things we watch out for with ibrutinib. Acalabrutinib really has all of the same side effects but for many of them, they don’t occur as often. And then, the tradeoff there is ibrutinib is given once a day and acalabrutinib is given twice a day. With venetoclax plus obinutuzumab with that regimen, you get a lot more hematologic toxicity. So, you see more lowering of the good white blood cell count, which is, obviously, a risk for infections. That regimen comes with a risk of something called tumor lysis syndrome, which is where the cells can break down too quickly and cause damage to the kidneys, damage to the heart.

It can also cause some GI disturbance like some diarrhea, nausea, abdominal pain, things like that. I see there are a lot of side effects. And, of course, when I’m talking to a patient about treatment, we go over them in more detail than that. But I think the important thing is with all of these therapies, we do have ways to manage these side effects.

One thing I think is important for patients to remember is your doctor doesn’t know you’re having side effects unless you tell them. So, we know that people have these side effects. But if you don’t tell us that you’re having diarrhea or heartburn or things like that, we can’t help with it. And we have a lot of medicines that can help these things.

 

 

 

 

What Is YOUR Role in CLL Treatment Decisions?

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What Is YOUR Role in CLL Treatment Decisions? from Patient Empowerment Network on Vimeo.

What is the chronic lymphocytic leukemia (CLL) patient’s role in making treatment decisions? Dr. Jennifer Woyach explains frontline CLL therapies and how patients help guide the treatment decision that’s best for them.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

Dr. Woyach, what do you feel is the patient’s role in this conversation about treatment approaches?

Dr. Woyach:               

I think that, obviously, the patient is the most important part of the talk of treatment indications. Like I mentioned, sometimes we have the discussion of chemotherapy versus a targeted therapy. More often, the discussion is we have three approved frontline CLL therapies right now. We have two BTK inhibitors or Bruton’s tyrosine kinase inhibitors, ibrutinib, acalabrutinib.

And then, we have a BCL-2, venetoclax, that’s given in combination with an antibody called obinutuzumab. These are very different treatments in terms of side effect profiles, how they’re administered, how often they’re administered, just as an example. The BTK inhibitors are pills. And they’re meant to be given indefinitely. So, you start them with plans that you’re not going to stop them, unless the patient doesn’t tolerate them or they stop working. And so, with that type of regimen, you have the kind of burden of being on treatment for a long period of time.

But on the flipside, it’s very easy to start treatment. So, if you decide you want a BTK inhibitor, I write a prescription for it, it comes to your house, you start it. I usually see patients monthly for the first six months and then, we go to every three months. It’s very easy to start treatment.

The other type of treatment, the venetoclax plus with the obinutuzumab regimen, that’s the BCL-2 inhibitor with an antibody, it’s a finite therapy. So, people are treated for a year and then, they go off treatment. The flipside of that is they’re a lot more time intensive in the beginning. So, you have the IV therapy with the obinutuzumab. Venetoclax you, actually, have to ramp up the dose so patients have to come in weekly for the first five weeks, and they have to come in monthly for their infusions. So, it’s much more time intensive up front but then, you get to stop treatment. And so, those are considerations that I can’t answer for somebody.

I don’t know which one people would prefer and people prefer different things. So, we spend a lot of time talking about all of the different scenarios and what’s going to make the therapy work best for the patient.

 

 

 

 

Could CLL Be Inherited?

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Could CLL Be Inherited? from Patient Empowerment Network on Vimeo.

Can chronic lymphocytic leukemia (CLL) be inherited directly from parents? Dr. Jennifer Woyach discusses the likelihood of passing down CLL to children and the difference between genetic mutations and acquired mutations in CLL.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

We have another question from a patient who wants to know if their children will inherit CLL. Is there any link between inherited mutations and CLL?

Dr. Woyach:               

That’s a very, very common and really important question. I would say of the hematologic cancers, CLL is one with higher linkage in families, which means that people with CLL are more likely to have another family member with CLL though it’s still not very common.

And it’s very different from breast cancer or the solid tumors where we know that these specific mutations indicate families that are going to have risk of disease. There has actually been a lot of study over the years of families that tend to have multiple people with CLL. Unfortunately, there really have not been genes identified that are the reason for those family linkages. I think there has been only one family that I know of where they’ve actually found a gene that was likely the cause of multiple family members’ illnesses. So, yeah, there is no indication to test family members.

I tell people do not worry that you’re going to pass this to your children or your grandchildren. CLL is not something that we should be using as like a marker of whether you should have kids or should have anything like that.

So, maybe a little more likely in family members but not enough to really be worried about that.

Katherine:                  

What are the differences or difference between inherited and acquired genetic mutations?

Dr. Woyach:              

So, inherited mutations are those that you get from your parents. And there are lots of inherited mutations that, actually, can predispose to cancer. Specifically, I mentioned the TP53 mutation and CLL cells. Well, there are also people who inherit a TP53  mutation have risk factors for multiple cancers. And CLL, specifically, every mutation that we talk about is an acquired mutation. So, that’s also known as a somatic mutation. So, they’re mutations in the cancer cells. But if you did DNA sequencing of the normal cells, they would not be there.

What Does It Mean to Have High-Risk CLL?

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What Does It Mean to Have High-Risk CLL? from Patient Empowerment Network on Vimeo.

What does high-risk chronic lymphocytic leukemia (CLL) mean exactly? Dr. Jennifer Woyach explains the meaning of high-risk CLL, factors in determining disease progression, and the impact on treatment decisions.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

We have a patient question. I have 17p deletion. Should I be worried?

Dr. Woyach:               

So, 17p deletion is usually associated with more aggressive disease biology almost always associated with that unmutated IGHV. The reason I bring that up is there are a very small subset of patients who have 17p deletion and mutated IGHV who, actually, have pretty indolent or slow growing disease.

People who don’t, which is the majority of them with 17p deletion, do have a shortened time to treatment and shortened survival with most of our current therapies. There have been a lot of advances though in the treatment of 17p deleted CLL. And may of our newer therapies can very much prolong the remission time in the lives of patients with 17p deletion.

Katherine:                  

Dr. Woyach, how do these chromosomal changes affect disease progression and prognosis?

Dr. Woyach:               

So, the markers that are associated with more aggressive disease biology usually are going to be associated with people that need treatment within the first few years after diagnosis, especially those people who have 17p deletion, 11q deletion, unmutated IGHV.

Katherine:                  

What exactly are prognostic factors? Would you define that?

Dr. Woyach:               

Sure. Prognostic factors, and I mentioned three of them, the IGHV, FISH, and the TP53 mutation, are ones that have been studied extensively and shown that the presence of this marker or some change in this marker is associated with a change in the biology of the disease or in the response to therapy.

Katherine:                  

How does the identification of these changes or mutations affect treatment options?

Dr. Woyach:               

Well, right now, we’re lucky in CLL because we have a lot of treatment options. I would say the most important changes when we’re talking about somebody with CLL that is about to start their first treatment is the decision of whether chemotherapy is ever appropriate. So, almost everybody with CLL now is treated exclusively with targeted therapies.                              

So, nonchemotherapeutic options. There are some people who are young, and in CLL terms that means under the age of 65, who have mutated IGHV and who otherwise have good genetic list disease. So, normal chromosomes of the 13q deletion, no TP53 mutation. That small subset of patients, actually, has the potential to be cured with a specific type of chemotherapy. It’s called FCR or fludarabine, cyclophosphamide, rituximab. So, for those young, healthy patients, it’s really important to know those risk factors to know if they are in that group that has that potential for cure.

The converse to that is if patients don’t fall in that group, they probably shouldn’t receive chemotherapy as their first treatment, because it’s not as effective as our other therapies.

Katherine:                  

Yeah. It makes sense.

Dr. Woyach:               

And then, even in the future with first and other treatments with novel therapies, we know that patients with 17p deletion and TP53 mutation tend to have a shorter response time. And so, what I use that for in my practice is I know that those are people that I really have to be sure that we’re following them closely, taking any signs of progression seriously, and always have a back-up plan for what we’re going to do if this treatment doesn’t work.

What Tests Should CLL Patients Insist They Receive?

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What Tests Should CLL Patients Insist They Receive? from Patient Empowerment Network on Vimeo.

Which chronic lymphocytic leukemia (CLL) tests are most critical in CLL care? Dr. Jennnifer Woyach details the key tests, what the tests identify, and how they help provide optimal care personalized to each patient.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

The goal of this program, Dr. Woyach, is to provide the confidence and tools for patients to advocate for the essential tests to get the best care personalized to them. Are there specific tests that patients should make sure they have?

Dr. Woyach:               

Yeah. In CLL, I would say there are three that are very, very important before starting treatment. The first is something called the IGHV mutational status.

What that is defined as is the changes in the variable region of the immunoglobulin heavy chain. That’s a big mouthful that doesn’t mean a lot to most people. So, I’ll give you just a little background on what that really means biologically and then, what that means clinically. So, every B lymphocyte, so a normal B lymphocyte and a CLL cell, has receptors on the surface of the cell that allow it to interact with the environment. And in a normal B lymphocyte, this is really important for the immune system. So, bacteria, virus, something is in the body and the B cell surface receptor is going to be able to recognize that that’s not supposed to be there and then, do something about it.

In CLL, the surface receptors don’t do a lot of interacting with the outside environment but they’re still present there. And in a normal B cell development, the B cells are initially formed in the bone marrow.

And at the time that they’re formed, every one of those receptors is exactly the same. So, we can do DNA sequencing on those receptors and you’ll see that every one is identical. So, during a normal development of a B cell, it undergoes this process that’s called somatic hypermutation, which is where those receptors mutate or change. And that’s important because then, they can recognize different things. And so, you end up with this whole repertoire of thousands or millions of B cells that all are a little bit different and can recognize something different.

So, CLL cells, they’re all clonally related to each other. They’re all going to have the same receptor on their surface. And about 60 percent of the time that receptor is different than the newly born B cells. And so, this is probably a little bit more simplistic than it actually is. But the way we think about that is that those B cells or those CLL cells, which we call mutated because they underwent that mutational process, we think that that means that they come from a more mature initiating cell.

And they tend to be less aggressive, more slow growing. The other 40 percent of patients, if you look at the receptor on their surface, it’s exactly the same as the new B cells in the bone marrow. And we call those IGHV unmutated because they haven’t done that mutational process. And they behave very differently. So, in mutated CLL, only about half of people will ever need therapy in their lives. An average time from diagnosis to first treatment is about 10 years. In contrast to those patients who have unmutated IGHV, basically, all of those people will need therapy at some point in their lives. And average time from diagnosis to first treatment is about three years.

So, you can see how it really breaks people up into two very different categories of disease.

So, that’s the first test and one that’s really important. That’s also one that doesn’t change during the course of the disease. So, if somebody is diagnosed with mutated CLL, it’s always mutated. So, the next marker that’s important is, actually, chromosome changes. So, we know that there are a few different recurrent chromosome abnormalities in CLL that are common and important prognostically. So, one of these is a deletion of part of chromosome 13. It’s called a 13q deletion. It indicates, again, very slow-growing CLL. Patients how have normal chromosomes also are very good disease biology.

Some people have an extra copy of chromosome 12. That’s called trisomy 12, and that’s an intermediate marker. And then, there are two markers that are associated with a little bit more aggressive CLL. One is a deletion of proto chromosome 11. That’s called an 11q deletion.

And the other one is a deletion of proto chromosome 17 called a 17p deletion. These are all abnormalities that are important to test for. And the way that we test for these is something called FISH testing. And FISH stands for fluorescence in situ hybridization. And it’s a way to use an antibody to look for specific abnormalities in the CLL cells. So, that’s important. And another thing that can be done at specialized centers is something called stimulated cytogenetics. So, I mentioned to you with FISH testing, we’re looking for specific abnormalities with antibodies. But the things that we don’t test for we’re not going to see.

So, if they have a chromosome change that we don’t have an antibody looking at, we’ll never detect it. And we know that patients with CLL who have what’s called a complex karyotype, which is three or more chromosome abnormalities, they also have more aggressive disease.

So, like I said, at specialized centers, we can do what’s called a stimulated karyotype, which is where we look at all of the chromosomes. So, that’s FISH testing and karyotype. And then, the last thing is, actually, doing DNA sequencing for a specific mutation called a TP53 mutation. And TP53 is an important tumor suppressor protein. And it is mutated quite commonly in CLL. About 8 to 10 percent of patients at the time of first treatment and, actually, up to about 40 percent of people later on in the course of the disease. Most of the time, we see TP53 mutations occur at the same time as 17p deletions. About 80 percent of the time, those occur together but they can occur on their own.

So, that’s the third test that’s often helpful, especially prior to starting treatment.

Katherine:                  

Do patients need to be retested over time?

Dr. Woyach:               

Yeah. So, for the TP53 mutation and for FISH, it’s important to test for those before each line of therapy. Because those are so important in indicating disease biology and, specifically, with the 17p deletion and TP53 mutation, those indicate patients that are likely to not have as good of a response to treatment. It’s always important to check for those prior to therapy.

What Should You Know About CLL Genetic Testing?

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What Should You Know About CLL Genetic Testing? from Patient Empowerment Network on Vimeo.

In chronic lymphocytic leukemia (CLL) diagnosis and disease management, genetic testing plays a key role. Dr. Jennifer Woyach explains what is examined in CLL genetic testing, the timing and administration of testing, and testing advances.

Dr. Jennifer Woyach is a hematologist-oncologist specializing in chronic lymphocytic leukemia (CLL) at Ohio State’s Comprehensive Cancer Center – James Cancer Hospital & Solove Research Institute. Find out more about this expert here. 

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Transcript:

Katherine:                  

Before we get deeper into our conversation about genetics, there are a few terms that patients are often confused by. As a primer, I thought we could start by defining some of these terms. First, what is genetic or molecular testing?

Dr. Woyach:               

So, all cancer cells will have a collection of mutations or abnormalities in the DNA that either make the cell a cancer cell or make it behave in a certain way. And so, these mutations are referred to as the genetic abnormalities of the CLL cells. So, when we talk about genetic testing in CLL, we use it to mean a number of things. We can use it to look specifically for types of mutations so types of genetic abnormalities.

 We also sometimes use that as a kind of catch-all term like genetic or molecular testing also to refer to looking at changes in the chromosomes inside of a CLL cell. That’s also called cytogenetic testing. And then, we also use a number of tests in CLL where we look at specific, not necessarily abnormalities, but just changes in the cell that can indicate a certain type of behavior.

Katherine:                

How is this different from genomic testing?

Dr. Woyach:               

So, genetic and genomic testing, I think, are usually used interchangeably. But sometimes, we use them in different contexts but they really mean the same thing in this case.

Katherine:                  

Okay. And what is a chromosome change?

Dr. Woyach:              

So, as you might remember from biology class maybe a long time ago, as it was for me, inside a cell, so a normal cell or a cancer cell, you have the nucleus, which holds the DNA.

And the DNA is organized into chromosomes. And so, when a cell goes through division, it takes those chromosomes, copies them and then, breaks them apart into two different cells. So, changes can happen in the level of the DNA itself. So, a mutation where one base is changed to something different. So, that would be just like a single nucleotide change. And that’s something you’re not going to see as a change to a chromosome. Another thing that can happen in CLL and in other cancers, too, is that during that process of cell division, an entire chromosome could be duplicated. It could be absent.

More commonly, parts of chromosomes can change. This is all because cancer cells just do a very poor job of editing their division.

An in normal cells, there are multiple steps along the way from the process of copying the genes to copying the chromosomes to doing the division. And every step along the way, if something happens incorrectly, which happens a lot, the cell usually just dies. But a cancer cell is not going to do that because it has so many signals that keep telling it to stay alive that it can tolerate a lot of different abnormalities. And so, you end up with cells that are just very different from what you would see normally.

Katherine:                  

All right. Well, that’s a great way for us to start. Let’s go into the discussion of the relationship between testing and CLL. How is testing administered?

Dr. Woyach:               

So, almost all testing, in terms of molecular genomic testing in CLL, can be done on a blood sample. So, that’s one important thing.

The CLL guidelines recommend that testing for certain prognostic factors be done before the administration of therapy. So, at the very least, before somebody starts treatment, they should have these tests performed. In my practice and I think most CLL specialists find it really helpful to do these tests, not necessarily just at the time of treatment but really at the time of diagnosis or the time we first see the patient because CLL is a very heterogenous disease, which means that it behaves very differently in different people. So, there are some people that are diagnosed and will go 10 or 20 years before they need any treatment.

And many don’t need treatment at all. Whereas other people are very likely to need treatment within the first few years after diagnosis. Some of the genetic tests that we do can help counsel patients on where they’re likely to fall in that spectrum.

And so, I think that’s helpful for people to know early on in the disease course. But really, the tests can be performed at any time before treatment

Katherine:              

Have there been advances in testing?

Dr. Woyach:               

Absolutely. I think in every cancer, we’ve learned so much more about the biology of the disease, specific mutations that cause specific behaviors of cells, and really much more in CLL about the common genetic changes and what those means to response to therapy.