What is the Best Treatment Approach for Patients With Relapsed/Refractory FL?


At the 2020 Great Debates and Updates in Hematologic Malignancies in Los Angeles, California, Elizabeth Brem, MD, UC Irvine Chao Family Comprehensive Cancer Center, Orange, California, debated John Leonard, MD, Weill Cornell Medicine, New York, on the best approach to treating patients with relapsed/refractory follicular lymphoma (FL).

Dr Brem argued in favor of chemotherapy and or stem cell transplant-based regimens versus non-chemotherapy approaches.


My name is Elizabeth Brem, I'm an assistant clinical professor at UC Irvine. I'm here at the Great Debates and Updates in Hematology in Los Angeles. We talked a bit this morning about relapsed/refractory follicular lymphoma, and when to use different modalities of therapy.

A lot of the discussion centered around how for different patients, depending on when they relapse and what they've gotten before, you may choose a different therapy. For example, there are some patients who get a really long remission from their initial chemoimmunotherapy, and those are patients who you might want to think about using chemoimmunotherapy again.

I showed the data from the GADOLIN study, which looked at bendamustine with obinutuzumab, 6 cycles of sort of an induction, and then obinutuzumab maintenance, and showed that compared to bendamustine alone in patients with prior therapy, there was improvement in progression‑free survival. There was a suggestion of overall survival, but of course that was a secondary end point.

For those patients who may be back in the day got R‑CHOP, got RCBP, those are patients who you may want to think about using chemoimmunotherapy again, particularly bendamustine‑obinutuzumab.

Then you have a different subset of patients. These are the ones who relapse very quickly after their first chemoimmunotherapy, and that's what we call either lack of EFS 24 or POD 24. These are patients who within 24 months of their first therapy have progression and need to be treated again. These patients, we know generally speaking, do not do as well.

We don't know what the optimal therapy is for these patients. There's an ongoing intergroup study trying to figure out do these patients benefit from a change of chemotherapy, or should you be giving them something more targeted, like a PI3‑Kinase inhibitor or lenalidomide‑based therapy? Again, we don't know, and that's the whole point of the study.

The frustrating part about this is even though we know that the patients who relapse on the early side don't do as well, it's hard to predict who those patients will be ahead of time. If you look at some of the traditional things like the follicular lymphoma IPI, it doesn't necessarily select out these patients. We're sort of stuck right now knowing who they are retrospectively on the back end.

But, there is some evidence that these patients who need to be retreated relatively early, we looked at some data from Carla Casulo, where she looked at the CIBMTR and the National Lymphocare Registry and showed that patients who relapse on the early side who can get to autologous transplant, may have better outcomes with transplant versus not doing an autologous transplant.

We also looked at some European data showing a similar trend. Again, these are retrospective. You could argue that the patients that went to auto were shown to be chemo sensitive, so you selected out a good population, but it's at least something to be considered, particularly in the younger patients who relapse within the first 2 years.

The other modality that I talked about a little bit was CAR‑T cell, though it's early for follicular lymphoma. Patients with transformed follicular lymphoma have similar outcomes to diffuse large B‑cell lymphoma, but when you look at follicular lymphoma without transformation, the response rates are pretty good.

They seem to be durable so far, but again, we're talking about a handful of patients that have been published on the order of 10 to 20, and limited follow‑up, so I think too soon to tell, particularly in light of the toxicity we know associated with those therapies.

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