Podcast appearances and mentions of Michael E Williams

Please join us Right Now, December 27 at 11:00AM PST as Actor Mueen Jahan, Producer, Broadcaster, Actress Pat Prescott and Founder/CEO Comedy Act Planet, LLC Michael E. Williams joins host Ron Brewington on "The Actor's Choice."

we're talking Comedy from a black perspective. The legacy. The heritage. And who better to sip coffee with than Michael E Williams - Hall of Fame promoter/producer of comedy and founder of the historic, legendary Comedy Act Theater in Los Angeles where many of your favorite comedy stars got their start. We'll talk about comedy as art.... black comedy history and Michael's upcoming book chronicling his legacy of bringing laughter to the world. This is a historic cultural gem!!!

Michael Williams is one of Canada's most esteemed media personalities and on Loc Talk he opens up about life, the early years and so Much more!

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Michael Williams talks about new research and advances in the field of lymphoma, including 3 recent U.S. FDA drug approvals. The research discussed was presented at the 2020 American Society of Hematology Annual Meeting, held virtually December fifth through eighth. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. View Dr. Williams’ disclosures at Cancer.Net. Dr. Williams: Hello. This is Dr. Michael Williams. I'm professor of medicine at the University of Virginia Health System in Charlottesville, Virginia, and I'm pleased to welcome you to this podcast for Cancer.Net. I'm reporting on some of the exciting updates that were just presented at the American Society of Hematology Annual Meeting. Typically, this is a meeting of 30 or 35 thousand clinicians and investigators from around the world. This year, as with so many meetings, we met virtually, but I would say very successfully done. Lots of exciting new data, and I'll try to give you a glimpse of what some of the progress has been. Before I start, I'll mention a few disclosures. So I have research grants that are awarded to the University of Virginia for clinical research from Celgene, Janssen, Pharmacyclics, and TG Therapeutics. And I have served as a consultant for Celgene, Janssen, and Pharmacyclics, as well as Kyte Pharmaceuticals, which is a division of Gilead. So the advances this year weren't just at the meeting. There were 3 new drug approvals in the past 6 months for lymphoma. Tazemetostat, which is an EZH2 inhibitor, was approved for relapsed/refractory follicular lymphoma patients who have a mutation in a gene called EZH2. So they showed good tolerance of this treatment with high response rates in these patients with the mutation. So it provides another important treatment option for people with relapsed follicular. A new approval for relapsed diffuse large B-cell lymphoma was a novel monoclonal antibody called tafasitamab given in combination with lenalidomide that also showed good responses and generally very good tolerance in people with relapsed aggressive lymphoma. So a welcome addition again to our treatment options. And then finally, a chimeric antigen receptor T-cell therapy or CAR-T was approved for relapsed/refractory mantle cell lymphoma. And I will say a bit more about that agent as we get into the discussion about CAR-T therapy for mantle cell. The first abstract presentation that I want to mention is in chronic lymphocytic leukemia or small lymphocytic lymphoma which, of course, is really 1 disease. It's just a spectrum of whether you have more of a leukemic phase or a lymph node enlargement component to your disease. Treatment in CLL has really shifted in recent years away from cytotoxic chemotherapy and is now well established that most patients needing treatment, whether for newly diagnosed disease or for patients who have been previously treated with other regimens, that targeted therapies such as Bruton tyrosine kinase inhibitors or a BCL-2 inhibitor venetoclax can get very high response rates. There's been interest among many groups in testing combinations of targeted drugs, and we heard an update of a report called the CAPTIVATE study that combines ibrutinib plus venetoclax. Both of these are oral agents. As a randomized study for patients with CLL who need treatment and have not been previously treated for their CLL. And what this study did was provided a combination of the 2 drugs as first-line therapy, and they showed that after a period of about 12 cycles of combined treatment, that you had very, very high remission rates. They used a very sensitive method, a molecular method, to detect minimal residual disease. And if patients were in a deep molecular remission, so undetectable MRD at the end of treatment, they were randomized to continuing with either no therapy or with just ibrutinib alone. And it was found that after a year, there was really no difference. So it shows that with combination therapy, you can get a deep enough remission to have a durable and ongoing response for those patients. They also randomized those who still had detectable residual disease to either ibrutinib alone or a combination of ibrutinib plus venetoclax, and they showed that their outcome at the end of treatment was likewise similar. So it shows a very good non-cytotoxic-chemotherapy-based approach to treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma. So the second item I wanted to bring your attention was for another form of indolent or low-grade non-Hodgkin lymphoma called Waldenstrom macroglobulinemia which is also identified as lymphoplasmacytoid lymphoma. And in this study, they used a combination of ibrutinib plus rituximab, an anti-CD20 monoclonal antibody, versus placebo with rituximab alone. So this study is reporting now long-term follow-up with more than 5 years since the onset of treatment initiation in 150 patients. So rituximab by itself was a standard of care for patients with Waldenstrom at the time the study was designed. We now know that ibrutinib can give very good responses, especially when given in combination with rituximab. And indeed, they showed that now with 5 years of follow-up, that the response in terms of the serum IgM level, which is a marker for activity of this disease, improvement in anemia as well as objective response rates were much improved with the combination of ibrutinib plus rituximab versus rituximab alone. They also showed that there was a delay in the time that a patient needed another line of therapy for progressive disease when they had that combination. So important long-term follow-up there confirming the safety and activity of ibrutinib and rituximab for that disease. And then finally, I'll give an update on 1 of many reports at this meeting on CAR-T cell therapy. So just to remind those of you who may not be so familiar with this, it's a technique of cellular therapy, wherein a patient who's got disease progression with follicular lymphoma or mantle cell lymphoma or diffuse large B cell lymphoma, the patient undergoes a procedure where T-cells are removed from their blood, and then in the laboratory, they are reprogrammed to attack the patient's lymphoma cells. So the reprogramming is done, the CAR-T cells, the chimeric T-cells are expanded, and then shipped back to the treating center where the cells are infused intravenously to the patient. There is already an approval of CAR-T cell therapy for diffuse large B-cell lymphoma as I mentioned. It is now approved CAR-T called axicabtagene ciloleucel or axi-cel is approved for mantle cell lymphoma, and what we heard at this in Boston. She gave an update on treatment of relapsed refractory follicular lymphoma and marginal zone lymphoma with the axi-cel CAR-T. So what Dr. Jacobson and her colleagues reported was for patients with relapsed and refractory follicular lymphoma, the overall response rate was 95%, with 80% of these patients being in a complete remission with ongoing follow-up. In those with marginal zone lymphoma, the numbers of patients treated were smaller, but they also showed high-response rates, 85% with 60% achieving a complete remission. And at a year of follow-up, most patients were remaining without evidence of disease progression. So a very promising advance in follicular lymphoma. It also raises the possibility that we may be able to use CAR-T cell therapy instead of traditional autologous stem cell transplantation for relapsing patients. But this is something that will have to be tested in formal clinical trials before becoming established as a new standard of care. So by the end of the meeting, it was clear that progress continues at a very rapid pace across the fields of human logic malignancies, lymphomas, leukemias, multiple myeloma, and others. So it reminds us that it's important if you're dealing with 1 of these disorders that you make sure you've done your due diligence in getting another opinion if that's warranted, at seeking out clinical trials which help bring some of these most promising therapies to the clinic and help us advance the progress in treatment as rapidly as possible. So I'd like to thank you for your attention today and wish you all the very best in the year ahead. ASCO: Thank you, Dr. Williams.  You can find more research from recent scientific meetings at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show wherever you listen to podcasts. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/donate.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2019 American Society of Hematology Annual Meeting, held December seventh through tenth in Orlando, Florida. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center. He is also the Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. View Dr. Williams’ disclosures at Cancer.Net. ASCO would like to thank Dr. Williams for discussing this research. Dr. Williams: Hello, and thanks for joining us for this podcast. My name is Michael Williams. I'm Professor and Chief of Hematology/Oncology at the University of Virginia in Charlottesville. And I'm pleased to discuss some exciting advances in lymphoma that were presented at the American Society of Hematology meeting held in Orlando in December 2019. My disclosures are that my research group here at the university, through the university, has received research support from pharmaceutical companies AbbVie, Pharmacyclics, and Janssen, and I have received honoraria for speaking at conferences from Xian-Janssen in China. So what I'm going to talk about today are 2 reports about the management of localized diffuse large B-cell lymphoma, an update on a novel therapeutic approach for relapsed mantle cell lymphoma. And then, I'll finish with a brief introduction of an agent that is showing promise for treating highly resistant relapsed lymphoma that was presented in the plenary session during the ASH meeting. So let's start with localized diffuse large B-cell lymphoma. So DLBCL is the most common subtype among the many forms of non-Hodgkin lymphoma. Usually, people present with advanced stage disease. But as many as 25 to 30 percent may have a disease that's localized to just 1 site or a very localized area of lymph nodes, so these would be stage I or stage ll patients. And the first report that I'll comment upon was presented by Dr. Laurie Sehn at the BC Cancer Agency in Vancouver, British Columbia. So they did a retrospective review looking at 319 patients treated in British Columbia over the past 15 years. So these were patients who had a nonbulky mass, they were localized disease. And the treatment currently for this disease is that people get either 6 cycles of a regimen such as rituximab and CHOP chemotherapy or more limited chemotherapy. Typically, 3 cycles of R-CHOP followed by radiation therapy. The importance of this study is that it is exploring a mechanism to de-escalate therapy, if you will, by avoiding the use of the radiation therapy. So what they did, is patients with localized disease received 3 cycles of rituximab plus CHOP therapy and then underwent a PET scan. So PET scans, unlike CT scans, are nuclear-medicine imaging that shows the functional uptake of radioactive glucose by the sites involved by lymphoma. So if you become PET negative after the three cycles of rituximab, CHOP therapy, then it seems likely that you've got a very highly responsive disease, and you may be able to avoid radiation therapy. So they did the PET scan after 3 cycles, and for those who were PET negative, then those patients received 1 additional cycle of rituximab CHOP, and that was the end of their therapy. If they were still PET positive, then they moved on to radiation therapy to the involved area. So what they found was quite interesting that of the 319 patients, 254 were negative after their PET scan. And so went on, virtually all of them, to just getting 1 more cycle of rituximab CHOP as planned. The outcomes for those patients were that very few of them relapsed over the next several years. They followed patients now, for about four years or more, in most cases, and they found that the overall, 5-year progression-free survival was 88% for those who were PET negative. For the subset of patients who were still PET positive, and got the radiation therapy, their outcome was somewhat worse, in that there was only 74% who were still progression free. The overall survival for these patients was 90%, at 5 years, for those who were PET negative and 77% for PET positive. So what this study shows us, is that a PET scan after 3 cycles, can inform us about patients who are 90% likely to have good control of their disease, with just 4 treatments, and you can avoid the exposure to radiation therapy. Those who were still PET positive still did well: 3 out of 4 were still in remission beyond 5 years but not quite as good an outcome. So these are patients who may be candidates for an alternative approach to try to do better with their long-term cure rates. So that leads us to the second presentation that I want to discuss. This was presented by Dr. Daniel Persky on behalf of the Southwest Oncology Group, which is part of the National Clinical Trials Network, in the United States. So they had a very similar approach. They studied patients with localized Stage 1 or 11, nonbulky diffuse large B-cell lymphoma, and they got standard rituximab CHOP therapy, and then a PET scan after the third cycle. Just as in the paper I discussed from British Columbia. Those who had negative PET scans got one additional cycle of rituximab CHOP. Those who were still PET positive got involved-field radiation therapy and treatment with a radio-labeled monoclonal antibody. Essentially, a radioactive form of rituximab, which has given us a single dose about a month after they'd finished their involved-field radiation therapy and then they got a follow-up PET scan, thereafter. So this study went on for several years, at multiple sites around the country. They enrolled 132 patients, and of those patients, 110 were PET negative after their third cycle. So only 18 needed to go on to this additional radiation therapy and the systemic treatment with the radio immuno therapeutic called Ibritumomab tiuxetan. They followed these patients now for 4 and a half years, and only 5 patients have progressed, and only 2 have died of their lymphoma. So of those who progressed, 3 of them had gotten just the R-CHOP alone. There was another patient who was PET positive but declined getting the radiation therapy who progressed. And then, another patient who had only 1 treatment was rituximab CHOP but then went off treatment due to toxicity. So similar, and in fact, almost identical to the British Columbia report. Five-year freedom from progression of their disease was 87%, and the overall survival was 90%. So these patients can do quite well, since many times, the location for localized DLBCL is in the head neck. There can be significant late effects of radiation therapy. So I think these studies reassure us that patients with localized disease can have very durable outcomes and cure rates. It's important to note that there's a higher rate of late relapse beyond three years in patients with localized DLBCL compared to more diffuse extensive disease suggesting that there may be some differences in the biology of a localized disease. So very important data, and data that gives us the opportunity to de-escalate treatment in localized large cell lymphoma. So let's switch gears and talk about mantle cell lymphoma. There's been a lot of progress in this disease over the past decade. Much of it related to the use of nonchemotherapy targeted agents such as Bruton’s tyrosine kinase inhibitors including ibrutinib and the Bcl-2 inhibitor, venetoclax. There was a study reported last year by an Australian group led by Dr. Constantine Tam. This study was updated at the ASH meeting with a longer follow up. So these were patients with Relapsed/Refractory disease, heavily pretreated. Many of them, previously, having had intensive chemotherapy and a stem cell transplant. And half of them had mutations in a gene called TP53, which is correlated with frequent chemotherapy resistance and high relapse rate. And what they found by combining the targeted agents ibrutinib and venetoclax, that they got very high response rates. The majority of patients responded although, there were a few who were primarily resistant, and about a third of patients, actually, got very deep remissions. PET negative and negative for minimal residual disease detection. If you look at the subset, of the highest risk patients, with the TP53 mutation, half of them achieved a complete response rate, and some of these patients have had durable responses. There have been a few patients who've had deep responses, who've been able to come off treatment. And overall, the duration of response at 2 and a half years is 74%. But what this study shows us, is yet again, that these novel targeted drugs that are typically better tolerated than cytotoxic chemotherapy can have very good and indeed dramatic responses, and so is showing a lot of promise. It reminds us that in mantle cell, whether it's newly diagnosed or relapsed, that talking to your oncologist about clinical trial opportunities can often avail you of some of the most promising new approaches. And indeed, that's true for all forms of lymphoma, that clinical trial options should be part of the discussion with treatment planning. I'm going to finish by just mentioning another novel agent that is being applied to patients with highly resistant relapsed disease. This is a molecule called mosunetuzumab, and this is a bispecific antibody. So there are a number of these now that are in clinical development, and some are FDA approved for treating leukemias and certain lymphomas. This one is designed to basically connect a body's immune system, the T cells, with the B-cell lymphomas by using an antibody that can recognize each of those and bring them physically together. So this was presented by Dr. Steven Schuster; it was a multinational study of this bispecific antibody in patients with very aggressive relapsed/refractory lymphomas including, diffuse large B-cell and transformed follicular lymphoma. And what they found in this study, is that response rates were 64%, with 42% of patients achieving a complete remission. So it's still early, but quite promising because these are patients who had failed CAR T-cell therapy. They may have failed transplant, or they were patients who needed a treatment to bridge them over to get to a CAR T or another treatment such as an allogeneic stem cell transplant. The toxicities were generally manageable and similar to those seen with other bispecific antibodies. So it's early, but across subtypes of patients with aggressive and relapsed lymphoma, I think this is another promising molecule, that may well provide good therapeutic options via a clinical trial for patients who have very limited other options to manage their disease. So thanks again for joining this podcast. There was a lot of other exciting data that we didn't have time to go through, so I encourage you to continue learning about what's new in the field, discussing with your oncologist, or with a consulting specialist in lymphoma, to make sure you can avail yourself of the best in current diagnostics and therapeutics. Thanks very much. ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at podcast.asco.org. Cancer.Net is supported by the Conquer Cancer Foundation of ASCO, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor Dr. Michael Williams will discuss some of the new research in lymphoma that was presented at the 2018 American Society of Hematology Annual Meeting, held December first through fourth in San Diego, California. Dr. Williams is the Chief of the Hematology/Oncology Division and Director of the Hematologic Malignancies Program at the UVA Cancer Center, and Byrd S. Leavell Professor of Medicine and Professor of Pathology at the University of Virginia School of Medicine. ASCO would like to thank Dr. Williams for discussing this topic. Dr. Williams: Hello. This is Michael Williams. I'm a professor at the University of Virginia Health System in Charlottesville, Virginia, and I'm reporting today on some exciting advances in lymphoma that were presented at the Annual Meeting of the American Society of Hematology, which was held in San Diego, California in early December 2018. Well, there were a number of areas of lymphoma that had important reports, and I'm going to just give you a small sampling of these today. We'll start with a new treatment option for patients with follicular lymphoma. Traditionally, this type of lymphoma, when it's symptomatic and needs therapy, the treatment of choice has been chemotherapy combined with a monoclonal antibody such as rituximab or obinutuzumab. But investigators, in a multicentered trial, decided to test whether you could use a chemotherapy-free treatment approach for patients like this by using rituximab combined with lenalidomide, which is also known as Revlimid, as a substitute for chemotherapy. And this is based on the fact that Revlimid plus rituximab has synergistic activity in patients with relapsed disease, so maybe we could see acceptable, high responses when it would be compared directly with rituximab plus chemotherapy. So the way the trial worked is this. Patients who needed therapy, who had advanced-stage follicular lymphoma—they had never had any therapy before—were randomized to either the rituximab-lenalidomide combination or a rituximab-chemotherapy combination that could include the regimens CVP or cyclophosphamide, vincristine, prednisone, the same combination given with daunorubicin, or the CHOP regimen, or rituximab combined with bendamustine. So over 1,000 patients were treated in this multinational study and the goal of the treatment, of the study was to prove that, actually, the ritux-lenalidomide was superior to the chemotherapy regimens. So the results showed, not superiority, but comparability. The complete remission rate between rituximab-len and ritux-chemotherapy were really identical, 48 and 53 percent, and the 3-year likelihood that the patients were progression-free, so had had no recurrence of their disease, was identical as well: 77 to 78 percent. There was no difference in survival which was 94% at 3 years in both arms. The toxicities differed, however. There was more rash with the lenalidomide combination, whereas low blood counts and the need for growth factor support such as G-CSF was greater with chemotherapy. And it was also interesting that some of the traditional risk factors didn't seem to apply, as much, for lenalidomide. So what would be considered higher risk patients treated with chemotherapy, seemed to do somewhat better with the lenalidomide combination. The importance for a patient with untreated follicular lymphoma who needs therapy is that a chemotherapy-free approach with rituximab plus lenalidomide can be considered equivalent to rituximab-chemotherapy. It’s worth discussing this with your oncologist when you're considering what treatment to use initially. The next subtype of lymphoma that I want to discuss is diffuse large B-cell lymphoma, and there's 2 presentations that I'm going to summarize. One, in patients with advanced stage disease, meaning stage III or IV. This identifies patients who have disease both above and below the diaphragm, to make it stage III, or stage IV means they've got bone marrow or other sites of involvement such as liver or bone. And the question being asked in this trial, which was part of the International GOYA trial, will take just a moment to explain. So the original GOYA trial compared whether a newer form of anti-CD20 monoclonal, namely obinutuzumab, which is also called Gazyva, how that would compare with the standard established monoclonal antibody, rituximab. And the initial findings of this study found that there was no benefit for the newer antibodies. So rituximab and CHOP chemotherapy was equivalent to obinutuzumab and CHOP chemotherapy in overall outcomes. But there was an opportunity with this trial to answer a question that's been out there for many years, and that is how many cycles of treatment does one need? So the investigators took advantage of this large study which included 712 patients who were randomized to rituximab plus CHOP. Just over 500 of them received 6 cycles, and the remaining 186 received 8 cycles. Even the patients who got 6 cycles of CHOP chemotherapy also got an additional 2 doses of rituximab, so the immunotherapy monoclonal antibody was equivalent between the 2 arms. And the results of this showed that there was really no difference at all with a followup of about 3 years. Response rates were equivalent and there was no difference in the patients staying in remission. It didn't matter in terms of survival which was excellent in both arms. There was, however, more toxicity in patients who received 8 cycles, including cardiac problems, infections, etc. These results showed that, I think we can finally put to rest the use of 8 cycles of rituximab-CHOP chemotherapy for advanced-stage large cell lymphoma. It's been an unknown entity because we never had a direct comparison of these. So we can now say that 6 cycles plus the additional 2 doses of rituximab is a standard for advanced-stage diffuse large B-cell lymphoma. Now, what about patients who have limited-stage, so stage I or II diffuse large cell lymphoma? That means just a single lymph node area's involved or 2 adjacent lymph node areas. In the past, these were treated either with 6 cycles of rituximab-CHOP or sometimes cycles of R-CHOP plus local radiation therapy. And in this study, which took a long time to complete; it began in 2005, but it enrolled 592 patients who were then randomized to either 4 cycles or 6 cycles of treatment. Radiation therapy was not planned for any of these patients except for very specific locations of involvement such as testicular DLBCL where radiation therapy is a standard. So the take-home message after over 5 years of follow-up for patients on this study showed that 4 versus 6 were identical. So 89% of patients were still in remission at 3 years after completing treatment, and the overall survival was really impressive, 98 to 99 percent in the 2 arms. So there was no benefit with limited-stage favorable disease. Now, who are these patients? So younger than age 60, stage I or II disease, and normal LDH. They did not have bulky disease, meaning there was no nodal mass more than 7 and a half centimeters. So if you fit those criteria, then you can benefit from a de-escalation of treatment and be spared the additional 2 cycles of R-CHOP. Now, sticking with the topic of diffuse large B-cell lymphoma, a challenging problem in our field is for patients who relapse after their initial therapy, or in some cases, fail to respond to a treatment like rituximab-CHOP or an equivalent immuno-chemotherapy regimen. And a very exciting advance in the field, over the past few years, has been the development of chimeric antigen receptor T cells or CAR Ts. Traditionally, what we've done with patients who relapse or have resistant diffuse large cell lymphoma is to give them a second-line, high-dose chemotherapy regimen, and if they showed a good response to that, they could then go to a dose-intensive treatment with a follow-up consolidation by autologous stem cell transplantation. And with that, you can cure, overall, about 40% or so of patients. The CAR T-cell approach takes a very novel immunotherapy effort, and that is that a patient's own T-cells are removed from the peripheral blood, and then in the laboratory, they're modified and reprogrammed so they can attack the patient’s diffuse large B-cell lymphoma cells that are resistant to chemotherapy. So there were 2 important follow-up studies, each of them involved 1 of the agents, the CAR T-cell products, that are approved by the Food and Drug Administration for patients with relapsed or refractory diffuse large cell lymphoma. The first used the CAR T known as axicabtagene ciloleucel. It's quite a complex name, but it goes by the abbreviation of axi-cel or the trade name is Yescarta. So in this study, the investigators wanted to show that this is a treatment that can be extended to many centers with the product, the CAR T being made in a central facility by the pharmaceutical company. So it was a retrospective study of 295 patients at 17 international centers: a lot of patients across a broad spectrum of sites in North America and Europe. Virtually all the patients were able to develop and obtain a CAR T product. It included patients with some of the higher risk forms of the DLBCL such as double and triple-hit lymphoma. About 3% of patients died during the treatment, although only 1% of these were felt to be related to the treatment itself. The response rates were quite good, with about 80% of people responding. The complete remission rates at 30 days after the CAR T infusion were 47%. So it proved that you can use this centrally manufactured product. So the patients T-cells are collected at the local center, they're shipped to the manufacturing facility, the CAR Ts are generated, sent back to the home institution, and then infused. And I'll say a word in a moment, after I introduce the next paper, to explain some of the side effects of this treatment. So the second study was also presented at the ASH meeting and published simultaneously in the New England Journal of Medicine in early December 2018. So this used the second FDA approved CAR T known as tisagenlecleucel or Kymriah. In this study, there were 93 patients who were able to receive a CAR T-cell infusion, 40% of them achieved a complete remission, and another 12% had a partial response. And that a year after their documented response, two-thirds of these patients were maintaining the response, including 79% of those who achieved a complete remission. So this trial again confirmed across multiple centers that CAR T-cells can be an effective therapy. The side effects of both of these drugs can include something called cytokine release syndrome where the immunologic effects, essentially, release cytokines into the blood that can mediate a capillary leak, respiratory troubles, and low blood pressures, that can, in some cases, require intensive care unit support. This can be managed by other mediators that tamp down the cytokine effect such as an interleukin-6 antagonist. The other toxicity which is less well understood and problematic can be neurologic effects which can include confusion, speech alterations and even coma. But again, approaches and treatments to identify and manage this are being developed. So CAR Ts have become established. They're available at a number of centers, but it's important to consider this as a treatment option in the setting of relapsed or refractory diffuse large cell lymphoma. The long-term curability is still unknown, although it's encouraging that patients with very resistant disease who'd get a good response can maintain that response out to a year and more. So we're going to be very interested to see how the longer-term follow-up comes together. The final topic I wanted to mention today is Waldenstrom macroglobulinemia. So this is a unique form of indolent B-cell lymphoma where the lymphoma cells release a monoclonal immunoglobulin into the blood known as IGM. Now, IGM is a very large antibody, and because of that, when the levels are very high, patients can have problems with high viscosity or thickening of the blood, which can cause confusion, vision changes, sometimes respiratory problems. And these patients also can become anemic or develop enlarged lymph nodes or enlarged spleen. So one of the standard treatments for this disease is, again, the immunotherapy monoclonal antibody rituximab, but the responses are typically incomplete and somewhat short-lived. So it was exciting, a couple of years ago, when the targeted tyrosine kinase inhibitor, ibrutinib, which targets the bruton tyrosine kinase in malignant B-cells. This is an agent that's approved in chronic lymphocytic leukemia, and certain lymphomas such as mantle cell, marginal zone, as well as lymphoplasmacytic lymphoma or Waldenstrom macroglobulinemia. So here's the study. Investigators had shown that if you combine rituximab with ibrutinib, that the response rates were improved as compared with rituximab by itself. And in a follow-up study that looked at this over a longer period of time, these benefits of the combined therapy were confirmed. These included patients without prior treatment or with prior treatment, with either chemotherapy or rituximab. And there was a confirmed benefit for the ibrutinib-rituximab combination in patients, whether they had had treatment before or not, and regardless of certain genetic markers that we use to assess risk in Waldenstrom. It was also shown that because these treatments continue indefinitely, as long as patients are responding and tolerating therapy, that the response rates improved over time. The side effects of treatment with ibrutinib are well-known, now, after several years of use across a variety of diseases, as mentioned, and include diarrhea, sometimes rash. You can see problems with easy bruising or bleeding, atrial fibrillation, and sometimes skin rash, or muscle and joint aches. But most patients are able to continue therapy and to benefit from it over an extended period of time. So the combination of ibrutinib plus rituximab was shown to add benefit compared with rituximab alone, and again, is a treatment approach and option that you could consider whether you have previously untreated or relapsed Waldenstrom macroglobulinemia. So overall, it was a very exciting meeting. We've had practice-changing data presented, and I've given you just a sampling of those. I think it's important for anyone dealing with lymphoma, or related malignancy, such as CLL or multiple myeloma to be very encouraged by the progress in the field, the opportunity to get much better responses with less toxicity and with minimal or no use of traditional chemotherapy. So we're pleased to be able to offer these treatment approaches for our patients. And I thank you for your taking part in the podcast and hope you found it useful. Thanks again. ASCO: Thank you, Dr. Williams. Learn more about lymphoma at www.cancer.net. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. Cancer.Net is supported by ASCO’s Conquer Cancer Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at conquer.org/support.

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