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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.

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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.

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