Relapsed/Refractory Follicular Lymphoma: Sequencing Through Multiple Lines of Therapy


Key opinion leader Lori Leslie, MD, sheds light on the optimal sequencing of therapy throughout multiple lines of follicular lymphoma.


Lori Leslie, MD: Although this is FDA approved and a very reasonable choice for a patient with follicular lymphoma [FL], my personal approach would be quite different. Typically, I reserve anthracycline-based chemoimmunotherapy, such as R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], for patients who develop ... disease or who have a presentation that’s concerning for a more aggressive early transformation of FL that cannot be confirmed histologically. For example, if someone has an SUV [standardized uptake value] above 13 to 15, a particularly elevated LDH [lactate dehydrogenase], and Ki-67 over 30% to 40% on their biopsy, even if it’s a low-grade FL, those are patients I consider for R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone], followed by maintenance, according to the PRIMUS studies this patient received.

Otherwise, I typically favor using bendamustine-rituximab in a frontline treatment. The comparative data with BR [bendamustine, rituximab] vs R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] or a CVP [cyclophosphamide, vincristine, prednisone]–type regimens with the BRIGHT and ... study show that BR [bendamustine, rituximab] has at least similar efficacy to R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] in low-grade indolent lymphoma and an overall favorable toxicity profile.

In terms of the use of maintenance, the benefit of maintenance post-bendamustine has not been demonstrated as strongly as it has been with post–R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone] therapies. My preference is not to use maintenance after bendamustine-based therapy, especially for frontline FL. Once patients get into the relapsed/refractory setting, I typically use lenalidomide-based therapy. The most common is lenalidomide-rituximab, the R2 regimen. An obinutuzumab-based combination is also very reasonable and appealing in this situation, particularly if someone did get rituximab in the frontline setting and was on rituximab maintenance when they relapsed.

In terms of the combination of bendamustine-obinutuzumab, I use that in select, slightly less common groups of patients, mostly because the increased incidence of neutropenia with obinutuzumab compared with the type 1 antibody, rituximab, as well as the increased risk and prolonged lymphopenia that can be seen with bendamustine, raises concern for infectious complications, particularly in older patients with FL. In summary, the most common approach that I’ll take for this type of patient is an obinutuzumab-rituximab-type frontline therapy and then, if they relapse, a lenalidomide-based therapy in the second line.

The treatment landscape of relapsed/refractory advanced-stage follicular lymphoma is getting increasingly complex, including novel agents approved and also some recently taken off the market. If I have a patient who reaches the third-line setting, assuming they receive chemoimmunotherapy or maybe lenalidomide-based therapy, we investigate what their goals are. Is this a patient who wants the most active thing we can offer? Hopefully that’s a time-limited treatment to get maximum benefit and as long of a treatment interval as possible in the third-line setting. Or is this a patient who’s older and says, “I want minimal interaction with the medical community. I want to take a pill and get whatever mileage I can out of that.” Other patients might be concerned about compliance with an oral regimen and want more of a chronic approach than with an IV [intravenous] treatment. All these patient preferences play a significant role when you get to the third-line setting because we have a variety of treatments that we can offer.

Transcript edited for clarity.

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