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Moving Beyond R-CHOP in Large Cell Lymphoma

Gina Columbus @ginacolumbusonc
Published: Friday, Oct 14, 2016

Loretta J. Nastoupil, MD

Loretta J. Nastoupil, MD

Patients with large cell lymphomas have a standard approach of R-CHOP; however, those who fall under the activated B-cell-like (ABC) subtype are not likely to respond well to the regimen.

Alternative treatments for these patients are being investigated, such as the regimen of rituximab (Rituxan), etoposide phosphate (Etopophos), prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (R-EPOCH). Researchers are anticipating phase III results comparing R-EPOCH with R-CHOP, explains Loretta J. Nastoupil, MD, who shared updates in large cell lymphoma during the 2016 OncLive State of the Science Summit on Treatment of Hematologic Malignancies.

Combination regimens with R-CHOP are also being explored, including 1 with lenalidomide (NCT02285062) and 1 with ibrutinib (Imbruvica), a BTK inhibitor that has shown promise in chronic lymphocytic leukemia (NCT01855750).

In an interview with OncLive, Nastoupil, an assistant professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center, discussed these ongoing clinical trials and how practitioners can better identify high- and poor-risk patients with large cell lymphomas.

OncLive: What are the essential updates in the management of aggressive lymphoma?

Nastoupil: In terms of what is exciting or coming out in the next few months to 1 year in untreated large cell lymphomas, there are a number of randomized studies that are looking at building off of the backbone of R-CHOP. They are, essentially, introducing targeted agents or agents that we think might have higher efficacy in the historically considered poor-risk group, which is the ABC or non-germinal center large-cell lymphoma.

Historically, though somewhat controversial, we think that that might be a group that may not do as well with R-CHOP therapy. This is exciting and very promising that we might have alternative therapies that will enhance the efficacy. I briefly touched upon data looking at R-CHOP plus the addition of lenalidomide and R-CHOP with the addition of ibrutinib (Imbruvica). We think we are going to be promising options for patients of the non-germinal center subtype.

Going forward in the next 5 to 10 years in this space, what do you see on the horizon?

That’s a great question. We have struggled over the past 10 years to really improve upon R-CHOP. We still consider that to be the standard of care for the majority of patients.

We are doing a little bit better of a job in terms of identifying high-risk patients who we fear will do poorly with R-CHOP. What we have not clearly established is what the preferred alternative is for those patients. In my opinion, I still think those patients should be considered for clinical trials where they may have access to agents where we think hold promise, but we’re still awaiting the randomized study to see if there’s truly a better option than R-CHOP.

We are still struggling with the patients who are chemorefractory in terms of identifying alternative approaches that hold promise, but also will demonstrate improvement in survival. There are more promising options in the non-germinal subtype, based on the molecular profiling that’s been done, which demonstrates that there might be targeted agents that may be effective. What has been slightly disappointing is the duration of response may not be as adequate as we had hoped.

What seems to be promising at this time is the CAR (chimeric antigen receptor) T-cell therapy, particularly for those who are chemorefractory, but it does come with associated toxicities. Identifying the proper patient, and providing therapy that we think will be effective in minimizing or doing a better job managing the toxicity, is still the goal.

Can you expand on the ongoing studies that you’re excited to see the results of?

There will be a large randomized study that will be presented at this upcoming ASH Annual Meeting, which is a randomized trial of R-CHOP versus dose-adjusted EPOCH-R, which most recently has been touted as a possibility of overcoming R-CHOP. There will be a lot of interest in terms of whether there are various subgroups that might respond to 1 regimen versus the other. We have all been waiting a long time for the results, so the general consensus is that it’s probably going to be no different than R-CHOP.

That study will be coming out and could impact practice patterns. For instance, at our institution, we have a patient who is higher risk and we worry may not do well with R-CHOP. The default is leaning toward dose-adjusted EPOCH-R. This may shake things up a little bit if it truly is a negative study and shows that it is not a better option for those patients.

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