First-Line Chemoimmunotherapy for MZL and FL

Anthony Mato, MD, MSCE: Let’s jump to advanced stage disease and start off with a loaded question. What’s the standard of care for chemoimmunotherapy?

Lori A. Leslie, MD: That is very loaded.

Anthony Mato, MD, MSCE: We want our audience to stay awake during this conversation, so we have to go to the controversies as soon as we can. What is your standard of care with follicular lymphoma? Do you consider there to be 1 standard of care when we’re talking about chemotherapy? Is there anything molecularly or genetic about these tumors that would dissuade you from starting with chemotherapy?

Lori A. Leslie, MD: The frustrating thing about follicular lymphoma is we do not have good predictive and prognostic models. I’m very jealous of CLL [chronic lymphocytic leukemia], where we have great predictive and prognostic markers that we should always check before chemoimmunotherapy. But that really isn’t the case. The FLIPI [Follicular Lymphoma International Prognostic Index], FLIPI-2, and the M7-FLIPI, which considers 7 molecular features, can’t predict patients who are at risk of poor outcomes, which is progression within the first 2 years of chemoimmunotherapy.

In general, I do think chemoimmunotherapy is the standard for patients with symptomatic follicular lymphoma. The choices are whether to use bendamustine or a CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]-like backbone, whether to use rituximab or obinutuzumab, and whether to use maintenance or observation. My general approach is to use rituximab-based chemoimmunotherapy because in the GALLIUM trial, with the use of obinutuzumab over rituximab, there was increased nonrelapse mortality in patients treated with a bendamustine backbone, increased infections, increased infusion reactions, and increased neutropenia. In the follicular lymphoma frontline setting, where many patients do well for a really long time, the PFS [progression-free survival] benefit hasn’t yet convinced me to use obinutuzumab for the majority of patients in the frontline setting. What do you feel about obinutuzumab?

Anthony Mato, MD, MSCE: I agree with you. There’s no clear advantage to using it in that setting. The studies have been a little flawed in terms of leading us to data that can be convincing enough to make that switch. It’s more toxicity than clinical benefit, so I completely agree. Rituximab would be my standard of care, although there is no universal right answer to that question. What were you going to say about CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone]?

Lori A. Leslie, MD: That, too, has changed over the past few years. CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] was probably more popular a few years ago, but more recently, with the comparative data in the StiL and BRIGHT studies looking at BR [bendamustine, rituximab] vs an R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone]-like regimen, it seems that BR [bendamustine, rituximab] is noninferior, and even was superior in 1 of the studies with a different toxicity profile; overall favorable. In general, BR [bendamustine, rituximab] is probably my go-to in the front line. However, I hesitate a little using bendamustine in younger patients, because of the longer-term potential effect on the bone marrow of bendamustine if they’re going to need more treatment down the line. I also hesitate if there is any question of transformation, so I would do biopsy if there was an area on the PET [positron emission tomography] scan that was a little bit brighter. But even if that shows grade 1/2 follicular lymphoma, but maybe the LDH [lactate dehydrogenase] is a little elevated, or something about their clinical presentation makes me think they’re in an early transformation state, then that’s a patient for whom I would probably opt to do R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone].

Anthony Mato, MD, MSCE: You mentioned PET imaging. Is that a standard of care for you? Does every patient with follicular or marginal zone who’s about to start therapy get a PET?

Lori A. Leslie, MD: Yes. Standard of care, in my opinion, is to check every single patient with a PET scan at baseline to look for occult transformations.

Anthony Mato, MD, MSCE: I agree. What about the patients with marginal zone lymphoma who you’re thinking about giving chemotherapy? Is it the same options? Do you make any distinction about the CD20 antibody in that patient population?

Lori A. Leslie, MD: In general, I do not use obinutuzumab in marginal zone lymphoma. I don’t think that it’s as well studied there as in follicular lymphoma, so I would suggest that rituximab is less controversial in that space. Particularly with the splenic marginal zone and the extranodal marginal zone, a lot of times, rituximab monotherapy is adequate, and they might not need the chemotherapy. If I am going to do chemotherapy, I do a rituximab-based, and typically bendamustine is the partner. Though in similar situations, if I had a nodal marginal zone lymphoma, for example, and was worried something more aggressive may be going on, then I would do CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone].

Anthony Mato, MD, MSCE: We need to jump to the next section, but I have a yes/no question. Maintenance or no maintenance for follicular, with rituximab of course? And maintenance or no maintenance for marginal zone lymphoma? I’m just curious. We can poll each other.

Lori A. Leslie, MD: I’m a maintenance fan, because of the significant PFS benefit in the PRIMA study: 10 years vs 4 years median PFS. The landscape is changing so quickly. In the past 9 months, we have had 3 new drugs approved in follicular lymphoma, so that PFS may translate to something else—potentially OS [overall survival]—if you shift someone into a new era. What about you? Are you a maintenance or an observation kind of guy?

Anthony Mato, MD, MSCE: I agree with you, particularly in the follicular space. I also think if you delay progression, you allow progress to happen behind the scenes. Every 6 months, there’s a new drug approved in these diseases, so it opens the window for opportunities that might not have been there.

Transcript Edited for Clarity