Lawrence Kaplan, MD

“This study is important because R-CHOP [rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone] has been the standard of care for many years. CHOP, the chemotherapy backbone, has withstood challenges from more aggressive regimens in the past. The excellent clinical outcomes observed in phase II trials of dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [Rituxan]) raised expectations that this would be a more effective regimen for treatment of diffuse large B-cell lymphoma,” said Lawrence Kaplan, MD, of the University of California at San Francisco.

“There was no difference in event-free survival for the population as a whole, and R-CHOP was less toxic. But the devil is in the details, and it remains to be seen if there will be a difference in the correlative analyses,” Dr. Kaplan admitted. “This study is another example of promising phase II trials that don’t pan out, and while most patients with diffuse large B-cell lymphoma will not benefit from EPOCH-R over R-CHOP, it is still possible that molecular analyses could turn up a subgroup that benefits from the more dose-intensive EPOCH-R regimen. It is worth noting that the study patient population was more favorable than average, which could have had an effect on the study results.”

“Based on phase II and retrospective data, patients with primary mediastinal large B-cell lymphoma, double-hit, and HIV-associated lymphoma do well with dose-adjusted EPOCH-R, and the outcome of this trial will not likely change its use in those patients,” Dr. Kaplan added.

Additional Commentaries

Stephen Ansell, MD, PhD

Stephen Ansell, MD, PhD, of the Mayo Clinic, Rochester, Minnesota, commented: “There has been much discussion about whether more intensive therapy is important for all diffuse large B-cell lymphoma patients. This study shows it is not important for all patients, but further evaluation of subgroups may show benefit. We may see some benefits in activated B-cell [ABC] vs germinal center B-cell lymphoma. R-CHOP is good for 80% of patients, and perhaps more intensive therapy should be focused on high-risk patients. For now, R-CHOP remains the standard of care.”

“We have been waiting for a very long time for these results, which could have been potentially practice-changing, but that turns out not to be the case,” said ­Stefan Barta, MD, of Fox Chase Cancer Center, Philadelphia. “R-CHOP is still the established backbone of therapy for diffuse large B-cell lymphoma.”

I am surprised by the results and slightly disappointed. I hoped we would have a leap forward, but still nothing is better than R-CHOP for the majority of diffuse large B-cell lymphoma patients.

— Stefan Barta, MD

Tweet this quote

“When the trial was started,” Dr. ­Barta continued, “we knew dose-adjusted EPOCH-R was more cumbersome, required inpatient admission to the hospital, and was more toxic. Phase II studies, as well as a meta-analysis I did, suggested that EPOCH-R was more efficacious. I am surprised by the results and slightly disappointed. I hoped we would have a leap forward, but still nothing is better than R-CHOP for the majority of diffuse large B-cell lymphoma patients,” Dr. ­Barta acknowledged. “It could turn out to be better for ‘double-hit’ lymphoma.”

“For now, we have to go back to the drawing board and study the addition of biologic agents to R-CHOP. Two ongoing studies are looking at the addition of lenalidomide (Revlimid)—an ECOG [Eastern Cooperative Oncology Group] study in all comers and the RESORT study in the ABC subtype, which has a worse prognosis. Ibrutinib [Imbruvica] and venetoclax [Venclexta] will also be studied,” Dr. Barta noted. ■

Disclosure: Drs. Kaplan, Ansell, and Barta reported no potential conflicts of interest.