R-CHOP Remains Frontline Standard in DLBCL, Says Expert

John Burke, MD

The regimen of rituximab (Rituxan) plus CHOP chemotherapy (R-CHOP) has been the standard of care for patients with previously untreated diffuse large B-cell lymphoma (DLBCL) for several years, and it appears it will remain that way for now, despite recent research to find novel alternatives, according to John Burke, MD.

The results of the phase III GOYA trial showed that the addition of the anti-CD20 agent obinutuzumab (Gazyva) to CHOP (G-CHOP) in the frontline setting did not improve progression-free survival (PFS) compared with R-CHOP in patients with DLBCL.

“In terms of efficacy, there was essentially no difference,” said Burke, a hematologist/oncologist at Rocky Mountain Cancer Centers. He also noted that patients treated in the obinutuzumab arm of the study experienced slightly more toxicity than patients who were treated with R-CHOP.

OncLive: Could you begin by providing some background on the phase III GOYA study?

In an interview with OncLive, Burke discussed the current treatment landscape of DLBCL, future directions for the treatment of this disease, as well as exciting highlights from the recent 2016 ASH Annual Meeting.Burke: DLBCL is the most common subtype of non-Hodgkin lymphoma. We really have not made any advances in that disease since the early 2000s, when it was shown that adding rituximab to CHOP chemotherapy improved outcomes. Despite that advance, we still cure roughly only 60% of patients with DLBCL, leaving 40% of patients who still die of their disease. That is why there is this need for new and better therapies in DLBCL.

We have seen in chronic lymphocytic leukemia (CLL) that obinutuzumab was superior to rituximab, and there are data from the GALLIUM study showing obinutuzumab to be superior to rituxumab in follicular lymphoma.

With that as the background, we asked the question, “Can replacing rituximab with obinutuzumab in patients with DLBCL also improve outcomes in that disease?”

What were the most significant findings in this study?

What are the next steps following these results?

What other presentations at this year’s ASH meeting were you excited to see?

We conducted a randomized phase III study looking at patients with advanced DLBCL, who were randomly assigned to 1 of 2 groups: either R-CHOP, which is the standard, or G-CHOP, which replaced rituximab with obinutuzumab.In terms of efficacy, there was essentially no difference. The progression-free survival (PFS) in both arms of the study was the same, and in terms of toxicity, the obinutuzumab arm had a little bit more, such as lowering of neutrophil counts and platelet counts. It did not appear that replacing rituximab with obinutuzumab provided an advantage in patients with DLBCL, and this is in contrast to what we saw in follicular lymphoma, and what we already know is true in CLL.There was a hint of a little bit of a benefit in 1 subtype of DLBCL, called the germinal center B-cell subtype, and so that needs to be worked out a little bit more and looked at in more detail. But as of now, the recommendation to practicing physicians is not to change their treatment, and not to use obinutuzumab instead of rituximab. R-CHOP remains the standard therapy for this disease.The use of maintenance rituximab after autologous transplant in mantle cell lymphoma (MCL) improved progression-free survival (PFS) and overall survival (OS), so I think that’s a practice-changing study for MCL. In follicular lymphoma, in the GALLIUM study, using obinutuzumab with chemotherapy instead of rituximab did improve PFS. We don’t know yet if there’s an OS advantage, but I think that’s a potentially practice-changing study.

Another one that was a disappointing study, but still very important, is the one that showed dose-adjusted EPIC plus rituximab was not any better than R-CHOP in DLBCL. I think a lot of doctors now are using the more aggressive dose-adjusted EPIC and rituximab in their lymphoma patients, and we’ll find out if there was a subset that may have benefited. But according to the abstract at least, there was no benefit in the overall population. That sort of solidifies R-CHOP, again, as the standard in DLBCL.

And then CAR T-cell therapy in DLBCL is being reported out, and there are some very promising results there, as well.