Goy on Going Beyond R-CHOP in Large-Cell Lymphoma

Andre Goy, MD

For decades, R-CHOP has been the standard of care for large-cell lymphomas. While the chemotherapy regimen remains the backbone of treatment, new agents offer combination possibilities that could boost survival, said Andre Goy, MD, chairman and director, chief of lymphoma, and director of Clinical and Translational Cancer Research at John Theurer Cancer Center.

“There is life beyond just R-CHOP,” Goy said in a recent interview with OncLive. “The dream in oncology is to get rid of standard chemotherapy, but in large-cell lymphoma, we aren’t ready for that yet. We see all these agents being added to R-CHOP trying to improve survival and I think that is where the future is going.”

OncLive: What emerging therapies do you see potential for in combination with R-CHOP in large-cell lymphoma?

Bortezomib (Velcade), lenalidomide (Revlimid), and ibrutinib (Imbruvica) in combination with R-CHOP have all showed promise in the treatment of large-cell lymphomas, noted Goy. In his Q&A with OncLive, Goy explains the role of these agents with R-CHOP, how the use of R-CHOP has evolved, and which patients should be given the regimen based on new findings.Goy: Bortezomib has preferential activity in non—germinal center (GC) subtypes or ABC subtype of large-cell lymphoma. There is a phase II study that combines R-CHOP and bortezomib that was very promising. It sort of neutralized the poor prognosis feature of being a non-GC patient. This was no small feat. Additionally, there are larger trials ongoing in a randomized setting to see if the addition of bortezomib improves the outcome of R-CHOP as the debate regarding this is still open.

The second compound that I see potential for across a diversity of subtypes is lenalidomide. That was also found to have preferential activity in ABC subtype and the non-GC subtypes of large-cell lymphoma. The combination of lenalidomide with R-CHOP improved the outcomes of the ABC subtype and therefore, non-GC and ABC have similar outcomes. This is all being looked at in a number of large randomized trials to see if it will have a benefit.

How is the role of R-CHOP evolving in large-cell lymphoma?

The third compound that shows promise is ibrutinib. It also shows more activity, based on a preclinical study, in the ABC subtype. It also has similar promising results in a phase III setting. It is being looked at in a large randomized trial that was just completed using R-CHOP alone versus R-CHOP and ibrutinib in the frontline ABC subtype.I think it is important to be alert as to who should not receive R-CHOP. The patients who have very extensive disease, usually aggressive biological presentation, and higher Ki-67, in those patients we should look at MYC and BCL2—either rearrangement or expression or both. If they have double hit features these patients should be referred to a center that will give them more intensive therapy and not get R-CHOP. These patients do very poorly with R-CHOP.

What are the biggest challenges that remain in the treatment of large-cell lymphoma?

Patients that are double expressers more often have the non-GC subtype, and those patients should participate in a clinical trial to try and answer some of the questions and try and build beyond R-CHOP.Some of the challenges are in elderly patients. There is new data looking at a very large number of patients, showing that patients who are over 80 years old are very often not offered chemotherapy, even if they are fit. There is data now showing that it is feasible to give R-CHOP or mini R-CHOP to these patients and they can do pretty well. I think it is important that we think about this population, as incidence of large-cell lymphoma in this population has increased 500% over the last 10 years. This is an important population.

The patient with comorbidities in large-cell lymphoma is also a challenge. There has been some data trying to see what we can replace doxorubicin with. I think as much as possible we should try and keep the doxorubicin on board. What is going to be interesting in the future is that we have antibody-drug conjugates that are also being looked at in combination with R-CHOP, which could potentially improve the outcomes without too much toxicity. R-CHOP still remains a good foundation, but we have to build on it.