Treatment Alternatives to Chemotherapy in R/R DLBCL

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Andre Goy, MD, MS: Dr Maddocks, in the real world, if a patient fails R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], they will locally get R-ICE [rituximab, ifosfamide, carboplatin, etoposide] or something. And they come to see you; they have not done well. If you have obviously access to a CAR T [chimeric antigen receptor T-cell therapy] you’re going to try to do this. But what else would you do in that situation?

Kami Maddocks, MD: If they have access to CAR T and they’re a candidate for that, that’s an approved setting. If they’re not a candidate for that, in the last 6 months we’ve seen the approval of the BR [bendamustine, rituximab]—POLA [polatuzumab vedotin] regimen, so that would be an option. Other things to consider outside a clinical trial of course would be novel agents like ibrutinib in a non-GC [germinal center] type or lenalidomide over 1 of those agents.

Andre Goy, MD, MS: Nathan, do you want to comment on the POLA durability? The POLA regimen, for our audience, is the combination with bendamustine.

Nathan H. Fowler, MD: This was a very interesting study. It was presented by Laurie Sehn, and it was a randomized phase II trial that enrolled 2 groups of people, follicular lymphoma patients and large-cell lymphoma patients. In both of those groups, they had relapsed disease and were transplant ineligible. What they did was randomize patents to bendamustine-rituximab versus bendamustine-rituximab plus polatuzumab.

Interestingly, in a fairly small phase II trial, 40 patients on each arm, they saw both a benefit in progression-free survival [PFS] and overall survival with the addition of polatuzumab. Because of that, especially overall survival benefit, it resulted in FDA approval. If you look at the PFS, I want to say it was nearly triple PFS—again, not great. These patients were still relapsing, but your PFS went from 2 months to about 7 to 8 months with the addition of polatuzumab.

Andre Goy, MD, MS: Obviously, there’s the POLARIX study, which has tried to take advantage to bring this in the frontline setting. This study is enrolling, right? This is not completed.

Nathan H. Fowler, MD: I think it’s near completion, and we will hopefully see the results at an upcoming meeting.

Andre Goy, MD, MS: Another study of R-CHOP plus X.… It’s interesting because we have tons of...novel therapy, but there was an interesting paper presented in Lugano, Switzerland, and there will be an update at ASH [American Society of Hematology Annual Meeting & Exposition]...looking at the R² [lenalidomide, rituximab]…in the frontline setting in patients with large-cell lymphoma, who are not great candidates for chemotherapy or just as a window trial, and the response rate is very high. The CR [complete response] rate is a relatively impressive...shorter version of chemotherapy. Grzeg, what do you think?

Grzegorz S. Nowakowski, MD: It’s a very interesting strategy because with the targeted agents and the antibody, you can actually have quite a bit of response. In this study, everybody still received chemotherapy if they were candidates for additional chemotherapy. But overall, in this high-risk population, the results were actually better than expected, typically in those patients with high IPI [International Prognostic Index score]. Whether it will be successful in the future or not will depend on what’s going to happen with the chemotherapy later on. We can imagine that if somebody was to develop full chemotherapy-free regimen that was actually resulting in cures and disappearance of chemotherapy, we’d probably all be happy that this is something that will develop.

So far, the evidence suggests that a cure is mainly with chemotherapy. There’s limited evidence that targeted agents can actually cure patients at this point. But this is definitely something to watch. I know there is a plan for the next subset of the study where they will be extending the duration of targeted therapy and try to limit chemotherapy with very careful monitoring of those patients.

Additional benefits of this strategy are also that some patients can be much sicker when they present, and they’ll be high risk for initiation of chemotherapy. If this targeted therapy could be like a bridging or stabilization before they actually start chemotherapy, maybe they can actually tolerate chemotherapy later on better. So it’s an interesting strategy...

Andre Goy, MD, MS: I am...some older patients...aggressive ABC [activated B-cell] presentation...reduce the chemotherapy. That’s the interesting thing we didn’t mention when we were talking about frontline. The German studies have typically included the prephase treatment. Rituxan [rituximab], steroids, and a bit of vincristine. This is actually working really well because patients tolerate it easily, and they come on the eighth, and they’re ready to get chemotherapy. So this is something that might be practical to our audience.

Transcript Edited for Clarity

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