Research Highlights from the 2021 American Society of Hematology Annual Meeting, with Christopher Flowers, MD

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. Guests’ statements on this podcast do not express the opinions of ASCO. 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 data described here may change as research progresses. In this podcast, Dr. Christopher Flowers covers highlights from the 2021 American Society of Hematology Annual Meeting, held December 11 to 14 in Atlanta, Georgia. He discusses new treatments for diffuse large B-cell lymphoma, advances in immunotherapy, and a session on improving inclusivity in clinical trials. Dr. Flowers is the Chair of the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center and was appointed Division Head ad interim of Cancer Medicine in August 2020. He is also the 2022 Cancer.Net Associate Editor for Lymphoma.   View Dr. Flowers’ disclosures at Cancer.Net. Dr. Flowers: Hello. I'm Dr. Christopher Flowers, Chair of the Department of Lymphoma and Myeloma and Interim Division Head for Cancer Medicine at The University of Texas MD Anderson Cancer Center. And it's my pleasure to talk to you today about the highlights from this year's American Society of Hematology meeting. The ASH meeting this year was a very exciting meeting for lymphoma broadly across all of the lymphomas, with particular highlights around diffuse large B-cell lymphoma where there were some changes that may be changes in the standard of care in the year ahead. I was involved in one of these studies, the POLARIX study that I'll spend some time talking about, where I was the North American lead, and I've served as a consultant for Genentech-Roche in the conduct of that study and other studies related to drugs in their portfolio. The other set of studies that I will talk about are the studies around CAR T-cell therapy. And 2 of those studies, Dr. Jason Weston from my institution and MD Anderson were involved with and Dr. Weston was the senior leader on 2 of those 3 studies that I will talk about. So let's first talk about the first line in diffuse large B-cell lymphoma. Diffuse large B-cell lymphoma, as many of you may be aware of, is the most common type of lymphoma and the most common type of aggressive lymphoma. Back in the 1970s and 80s, the standard of care for CHOP therapy was developed. And that through the 90s, through a number of comparisons of clinical trials for chemotherapy, emerged as the de facto standard of care. In early 2000, the drug rituximab, the anti-CD20 antibody therapy, so our first form of immunotherapy, was added to CHOP. And R-CHOP therapy became the standard of care around 2002. And so it's really been about 20 years that that has been the standard of care for all patients or for most patients in the front line for diffuse large B-cell lymphoma. That's not been without challenges. There have been a number of clinical trials from 2002 to the present that have challenged R-CHOP, either by adding new therapies, like new targeted therapies looking at intensifying the CD20 antibody component, adding things like stem cell transplant or intensifying the chemotherapy-- and in some cases, focusing on subsets of diffuse large B-cell lymphoma, like the activated B-cell-like subset that are at poorer outcomes in the general population. However, none of those clinical trials really emerged to change the standard of care. And R-CHOP had remained the standard of care for patients. This year, as one of the late breaking abstracts presented at the American Society of Hematology meeting and followed up by a publication in the New England Journal of Medicine, one of our top premier journals, there was a study that looked at the substitution of vincristine, one of the drugs in CHOP, for the drug polatuzumab vedotin. Polatuzumab vedotin is what we call an antibody-drug conjugate, where that antibody binds to a cell surface marker on the lymphoma cells CD79B. And with that, binding is internalized into the cell. And the conjugate is a form of chemotherapy, MMAE, that is then taken into the cell with the antibody. And that antibody-drug conjugate was substituted for vincristine in the study. In the POLARIX study, it showed that it met its primary endpoint for the study, which was an improvement in progression-free survival, where the patients who got the polatuzumab in their chemotherapy with R-CHP had an improvement in progression-free survival of approximately 26% over the group that got R-CHOP. This is the first time to show an improvement in front-line therapy for patients with diffuse large B-cell lymphoma. And regulatory bodies will be looking at this to see whether this is approved in the first line in the relatively near future. The other major trials that were presented at this year's American Society of Hematology meeting in diffuse large B-cell lymphoma were trials looking at the second line of therapy for patients with diffuse large B-cell lymphoma. And in that second line, for patients who were fit and able, stem cell transplant has formed as standard of care for patients after R-CHOP therapy. As many of you may know, diffuse large B-cell lymphoma is a disease where the goal of treatment is cure. And with that first-line therapy, the therapies that are able to produce benefits in terms of progression-free survival are expected to go on to cure for those patients if those responses are durable in 5 years. Even when patients have relapse after their first-line therapy, there's the potential of cure in the second line. And stem cell transplant has been that curative approach that we've taken for many patients in the past. In this year's ASH meeting, there were 3 trials that compared the concept of moving on, after first-line therapy, to intensive chemotherapy followed by a stem cell transplant or to performing CAR T-cell therapy as that second-line therapy. As some of you may know, CAR T-cell therapy has emerged as really an exciting form of immunotherapy, a cellular therapy, that is approved for patients who are with lymphomas and some leukemias and being explored in other diseases. CAR T-cell therapy is a form of immunotherapy where we actually re-engineer cells. So we take the cells from the patient and then genetically re-engineer those cells so they attack a marker on the cell surface. I talked about CD20 antibody therapy. All of these CAR T-cell therapies are cellular therapies against the marker on the lymphoma cells called CD19. And so in these 3 trials that compared CD19 CAR T-cell therapy versus autologous stem cell transplant, 2 of those trials, 1 presented in the plenary session—and that was one of the ones that Dr. Weston participated in—was a study that showed that there was a benefit in progression-free survival for those patients who received CAR T-cell therapy over the approach to do stem cell transplant as that second-line therapy. There was a second trial, the TRANSFORM trial, that was also presented in one of the oral abstract sessions. That one presented interim analysis of their trial. They also showed a benefit in terms of progression-free survival. And then there was a third trial that was looked at in the late breaking abstract session. That one did not show a benefit for CAR T-cell therapy in that setting, using  tisagenlecleucel as a form of CAR T-cell therapy in that study. And perhaps the reasons why that did not show a benefit or differences in the trial design between those 3 trials, not as many of the patients were able to go on to CAR T-cell therapy in that third trial. And that was really expertly described and compared by Alex Hariri in a discussion of the plenary session. So really, 4 major trials in diffuse large B-cell lymphoma that we expect will change the standard of care. Likewise, there were a number of other exciting new immunotherapies that have been presented at this year's annual meeting, namely studies looking at bispecific antibodies. And so these are antibody-based therapies in a number of different trials that both engage a portion of the lymphoma cell. And then as the other portion of the bispecific, so meaning two, that other portion engages T cells. So it brings T cells into the tumor to be able to attack the lymphoma cells. And so there are a number of exciting therapies that are on the horizon for lymphomas looking at that. And those were also presented at the ASH meeting. The last thing that I'd like to highlight from this year's annual society meeting was a joint session that looked at the role of clinical trials and ways that we can actually improve clinical trial design for patients-- 1, to increase the diversity, equity, and inclusion that we see across clinical trials to make sure that all patients who are eligible are having equal access to trials and being able to participate, but also in terms of being able to modify the eligibility criteria that we use for clinical trials. One of the things that we've explored, particularly for those challenges that I described without advances in the front line for diffuse large B-cell lymphoma in the past, have been that some of the eligibility criteria for our past trials really were not including all the patients who were most likely to benefit from trials. And so Tom Witzig at this year's annual society meeting really presented an outstanding look at the eligibility criteria that we use for lymphoma trials, and trying to be able to address those in ways that help to allow more patients to participate in trials, and those who are most likely to need a trial to be able to benefit from the activities that are engaged in a trial. So I really appreciate all of your attention to this podcast. Exciting meeting this year for the American Society of Hematology Annual Meeting. And lots of things that will come to patients in the near future. And hope to be able to create advances that will help all of you in terms of your quality of life and well-being. So thank you all for your attention. ASCO: Thank you, Dr. Flowers. 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. 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