Research Highlights from the 2016 American Society of Hematology Annual Meeting, with Michael E. Williams, MD, ScM

January 12, 2017
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In today’s podcast, we’ll discuss some of the new research that was presented at the 2016 American Society of Hematology Annual Meeting, held December third through sixth in San Diego, California.

Transcript: 

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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.

In today’s podcast, we’ll discuss some of the new research that was presented at the 2016 American Society of Hematology Annual Meeting, held December third through sixth in San Diego, California. This podcast will be led by Cancer.Net Associate Editor, Dr. Michael Williams. 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 summarizing this research.

Dr. Williams: Hello. This is Dr. Michael Williams. I'm at the University of Virginia in Charlottesville where I lead our lymphoma group. I'm here to report on behalf of Cancer.Net some exciting news and updates from the American Society of Hematology meeting that was held in San Diego in early December.

So the meeting was really a very important one for the field, as I'm sure many of you are aware who have an interest in lymphoma. There's been just dramatic progress in the field over the past several years, with advances in understanding the biology of lymphomas at a more molecular and cellular level, advances in new treatment approaches—many of them related to immunotherapeutics and targeted drugs, rather than traditional chemotherapy and radiation therapy—and ways to, if not to completely cure some forms of lymphoma, better ways that we can keep them under control for much longer and indeed improve survival for those patients. So I thought I would go through just a few of the more common diseases and give the updates for those diseases with their advances that we heard at the meeting.

So the first I was going to comment upon is follicular lymphoma. This is one of the most common forms of non-Hodgkin lymphoma in North America. It's typically, in advanced stage, treated with a regimen of rituximab plus chemotherapy. The study that was presented by Dr. Robert Marcus from King's College in London was a multi-center study testing a new form of anti-CD20 monoclonal antibody, essentially a next generation rituximab, in combination with chemotherapy. So this study compared previously untreated patients with follicular lymphoma, and they received chemotherapy with either rituximab or chemotherapy with the new type of monoclonal antibody called obinutuzumab.

And what they found in this comparative study is that the obinutuzumab-treated patients had higher response rates and that these responses appeared significantly more durable for the patients who got the newer antibody. As a result, it's now perfectly appropriate to consider an obinutuzumab plus chemotherapy approach, rather than rituximab for patients with advanced stage follicular lymphoma who need treatment. The obinutuzumab is already FDA approved in the United States for relapsed follicular lymphoma, so it's very possible that based upon this data it will soon have an indication for use in the frontline setting. So it's something to discuss with your oncologist if you have this type of lymphoma and are considering what treatment course should be pursued.

The second disease is the other common form of non-Hodgkin lymphoma in the US, and that is diffuse large B-cell lymphoma. This is a somewhat complex subtype of lymphoma. It tends to be more aggressive. It tends to require treatment in the majority of patients at the time of diagnosis. Many of these patients are cured with standard treatment which consists of rituximab plus CHOP chemotherapy. But there have been other chemotherapy regimens given with rituximab that have shown promise in earlier phase studies. One of these is a regimen called dose-adjusted rituximab plus EPOCH. That's E-P-O-C-H. And again, it's an acronym for the chemotherapy drugs used.

So this was a very large phase III study treating patients with newly diagnosed diffuse large B-cell lymphoma and comparing treatment with standard rituximab-CHOP versus the dose-adjusted rituximab-EPOCH. And with an average follow-up now of approximately 5 years, the finding was that when taken for the entire group of these patients, there was no clear benefit for the newer regimen of dose-adjusted EPOCH as compared with rituximab-CHOP. There was higher toxicity with the newer regimen. So this was somewhat disappointing that the new regimen didn't show a benefit to R-CHOP, but it's important to keep in mind that this is really the initial report and that further details will be coming out in the next 1 to 2 years looking at subsets of patients, those that we now know have higher risk of recurrence and failure to be cured with initial R-CHOP chemotherapy, for example, patients who express proteins in their cells called c-Myc or have a translocation in that gene or patients who have an activated B-cell type of diffuse large cell rather than a germinal center type. So those are just designations of some of the subsets that have lower and higher risk. So it's possible, as we get deeper into the analysis of this trial, that we may find subsets of patients for whom the EPOCH regimen may be preferred. But for right now, rituximab-CHOP remains the standard of care.

The third disease is one that my group has been involved in studying for many years, mantle cell lymphoma. So mantle cell has a variety of ways that it can be managed. It depends in part on the patient's disease presentation, their age, their general medical fitness in terms of other diseases that might coexist. For younger patients with mantle cell lymphoma, a standard approach is to do induction chemotherapy with rituximab plus a combination chemotherapy regimen. And since that's rarely, if ever, curative for mantle cell, we try to get a deeper, longer-lasting remission by consolidating that induction with high-dose chemotherapy and an autologous stem cell transplantation or an AUTO transplant, as it's often called. So even with that transplant, many patients will still relapse at an average of 3 to 5 years.

So there's interest in seeing whether we can prolong the remission for those patients, and one way that that's being studied is by giving maintenance rituximab, so maintenance immunotherapy with a dose of rituximab, given intravenously every 2 months for 2 to 3 years. So in a large French study, they studied patients with mantle cell lymphoma who were in their remission, who underwent a stem cell transplant and then randomize them to receive either receive maintenance rituximab for 3 years versus just observation without maintenance therapy. And the results of the study were really quite impressive. They showed not only a significantly improved progression-free survival, or other words, prolong period of disease control, but actually showed an overall survival advantage in favor of maintenance rituximab.

So given that, I think now it's appropriate for anyone with mantle cell lymphoma who undergoes autologous stem cell transplantation to receive 3 years of maintenance rituximab. One question might be, "Well, gee, is 3 years long enough? Is it more than we need?" We don't have details in that as yet, and so 3 years right now would be a recommendation based on this large study. There are newer markers being tested in mantle cell, and many other lymphomas, where we use so-called minimal residual disease. We look with very sensitive tests at the blood and bone marrow that can tell us if we have trace amounts of lymphoma left behind. Or, if those studies are negative, you can use them to monitor patients while they're in remission and if you see signs of early recurrence by these minimal residual disease tests becoming positive, then there is an opportunity to treat the patient again before the disease clinically relapses. So that's an area of very active interest in lymphoma and many areas of oncology. But for mantle cell lymphoma, for patients who are in remission after a stem cell transplant, maintenance rituximab is now a new standard of care.

The last disease I was going to mention really relates more to a type of novel therapy rather than the disease itself. Many of you, I'm sure, are familiar with CAR T cells, or chimeric antigen receptor T-cells. This is a very exciting new technique, where a patient's T cells, which is an important part of one's immune system that's involved in fighting cancer, among other functions. So the T cells from a patient are removed and they're reprogrammed at a molecular level to specifically attack a patient's lymphoma cells. And that was studied in a multi-center trial utilizing CAR T-cells in patients who had relapsed, refractory, aggressive lymphomas, mostly diffuse large B-cell. So patients who have failed rituximab plus chemotherapy such as CHOP, or they have failed a second or third time after other chemo or after a stem cell transplant, typically have very limited treatment options. So this was a study comparing the use of CAR T-cells as a cellular immunotherapy to treat refractory lymphoma.

What they found in the first 51 patients that were analyzed was a very high response rate of 76%, much better than would be expected with third or fourth-line chemotherapy or other antibody approaches such as rituximab or obinutuzumab. About 40% of the patients were maintaining that response out for several months and some of them quite durable. This is an experimental treatment. It's one that has a number of serious side effects, so patient selection is important in terms of whether it's appropriate, or whether a patient is eligible for this, but CAR T-cell therapy is a very exciting new direction in cancer immunotherapy. So one to be aware of if you're in a situation with recurrent diffuse large-cell lymphoma and other types of non-Hodgkin lymphomas.

So I'll finish by just reiterating my comment at the beginning, and that is that it's a very dynamic time in lymphoma treatment. We have many new drugs, some of which are now FDA approved. Others which are likely to be approved in the near future, that are very active for patients with relapse disease. They're allowing us to now start treating some patients without chemotherapy, at all, just, say, with rituximab plus a targeted agent such as lenalidomide, or perhaps ibrutinib. We can add these targeted drugs to chemotherapy regimens such as rituximab-CHOP or rituximab-bendamustine.

So the message you should take away from this is not so much the details of one or another particular regimen or targeted therapy, but keep in mind that it's important while you're discussing with your oncologist what a treatment approach might be, whether it's for a newly diagnosed or relapsed, as to whether you might be a good candidate for one of the clinical studies of the newer agents that are being tested. And if it's not available with your oncologist or in your region, sometimes you can obtain a referral at a nearby center where you may have those options. So it's always important to keep clinical trials in mind as you discuss treatment planning with your oncologist.

So with that, I'll close, and just say again, a very exciting time in the field, a very productive American Society of Hematology meeting this month, and I hope that you find Cancer.Net very useful, and are able to benefit from the information that's provided there. Take care.

ASCO: Thank you, Dr. Williams. To find more information about these topics, visit www.cancer.net.  And for more expert interviews and stories from people living with cancer, visit the Cancer.Net Blog at www.cancer.net/blog.

Cancer.Net is supported by the Conquer Cancer Foundation, which is working to create a world free from the fear of cancer by funding breakthrough research, sharing knowledge with physicians and patients worldwide, and supporting initiatives to ensure that all people have access to high-quality cancer care. Thank you for listening to this Cancer.Net Podcast.