Mantle Cell Lymphoma Maintenance Strategies

Anthony R. Mato, MD, MSCE: Brian, I want to switch to you now and talk about maintenance therapies in mantle cell lymphoma (MCL) because I know this is another area of controversy, and it depends on what regimen you were using to begin with and whether there's a value to maintenance. Tell us, first of all, what are the maintenance strategies that are available? Who should get maintenance therapy? And how are you making that decision? Let's take the answer out of the context of the [COVID-19 (coronavirus disease 2019)] pandemic because it's too easy to say we're in a pandemic, so we don't want to give rituximab to anybody. Pretend like we were able to do whatever we want. Where does maintenance fit in?

Brian T. Hill, MD, PhD: It's a great question because [there is] a lot of confusion about maintenance therapy, and it really does depend on the disease. We are probably familiar with the studies in follicular lymphoma that show, after response to chemoimmunotherapy, if you apply maintenance rituximab, a typical schedule would be 1 dose every 2 months for 2 years. We know that you can extend the median progression-free survival (PFS) by much more than 2 years. Probably about 4 to 6 years of additional remission with 2 years of maintenance therapy.

However, it's never been shown that maintenance therapy for follicular lymphoma improves overall survival. In that disease, it becomes complicated. MCL is different because there are actually several randomized phase 3 trials, both after chemoimmunotherapy and after autologous stem cell transplant, that show not only a PFS advantage but also an overall survival advantage to maintenance therapy, and in fact, after autologous stem cell transplant, it was 1 dose every 2 months for 3 years, which is a pretty long duration of maintenance. Yes, it's true that patients on maintenance therapy tend to get more infections, usually sinus infections, [which are] usually what we call nuisance infections. Yes, it's definitely true that in the COVID-19 era, rituximab does confer an added risk to severe pneumonia, but I think that most people in the field who treat MCL feel like it is standard of care to do maintenance therapy because of the proven overall survival advantage.

Anthony R. Mato, MD, MSCE: Whether you give R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone), or BR (bendamustine/rituximab), or more intensive regimens, you are still providing maintenance therapy? The backbone doesn't matter?

Brian T. Hill, MD, PhD: Well, good question. Most of the trials were done in the R-CHOP era or after autologous stem cell transplant. There's never actually been a randomized trial after bendamustine/rituximab to prove that there's a survival advantage, but it has become the de facto standard of care and is used as the standard arm or control arm, such as [in] the SHINE study (NCT01369069) that we just heard about. The control or standard of care arm was bendamustine/rituximab followed by 2 years of rituximab maintenance.

Anthony R. Mato, MD, MSCE: Alexey or Michael, [do] you want to say something?

Michael Wang, MD: Yeah. I think the maintenance therapy is very important in MCL. Maintenance therapy added to almost everything improved the PFS, and in the postauto transplant [setting], it improved the overall survival. Maintenance added to bendamustine/rituximab after bendamustine/rituximab and R-CHOP has shown, in many studies, to prolong the PFS, so it's very important.

Anthony, I really wanted to take this opportunity to ask the panel a question. We know that rituximab seems [to influence] antibody reaction of the current against the COVID-19 vaccine. We know that even after BTK (Bruton tyrosine kinase) inhibitors [as well]. You guys probably face the same problem. What are we telling our patients here? Should we stop the rituximab maintenance? Sometimes [with] BTK [inhibitors], should we continue? Of course, it should be a dialogue between the patient, the family, and us, but what have you guys been doing?

Anthony R. Mato, MD, MSCE: Matt, [do] you want to weigh in there?

Matthew S. Davids, MD, MMSc: Sure. I think we're in a very different era now than we were even just a few months ago. We have pretty widespread availability [of tixagevimab with cilgavimab], so we're trying to give our patients that. We also have treatments available for COVID-19 like [nirmatrelvir and ritonavir] if they get infected. I've been just proceeding as planned in CLL (chronic lymphocytic leukemia). If I need to use a CD-20 antibody, I will. If I have a patient on a BTK inhibitor, I'll continue it. That's been my approach.

Anthony R. Mato, MD, MSCE: [Does] anyone disagree, or [does] anyone have a different approach? I'm on the same page as Matt.

Alexey V. Danilov, MD, PhD: Me as well. I do really rely on the novel agents that we have and use the standard approach that we use in MCL and CLL regarding CD-20 antibodies.

Anthony R. Mato, MD, MSCE: Go ahead. Sorry, Michael.

Michael Wang, MD: For me, if the patient has been on long remission, and the risk of relapse is very low, I often pause the rituximab therapy.

Anthony R. Mato, MD, MSCE: Brian, I want to jump to a topic you and I have been working on for 8 years now: real-world data. This has become important because, [as] Michael already pointed out, some of the trials that we want to see to generate the data from a prospective perspective just aren't happening. In MCL, can you comment on the value of real-world data and highlight some things that we've learned from it that we haven't really gotten from the clinical trial setting?

Brian T. Hill, MD, PhD: Yeah, certainly. What we've seen in MCL, as we've been talking about, is that there is less consensus about what the optimal frontline therapy is. Because there [are] fewer patients, there are fewer head-to-head trials testing different regimens. One of the things we've been discussing was maintenance therapy, and because of different practice patterns, not everyone who received bendamustine-rituximab as frontline therapy, depending where they were treated, was actually placed on maintenance therapy. One of the real-world studies that's come out of various collaborations [has shown the] observation that, if you take this group of patients with frontline treatment [with] bendamustine/rituximab, there does look to be a PFS benefit and a trend towards survival advantage as well in those patients treated with bendamustine/rituximab. I think this is the type of evidence that is helpful in justifying the use of that type of regimen rather than going through the time and effort that would be required to do the proper study, which, unfortunately, was never done, comparing maintenance to no maintenance after bendamustine/rituximab.

Anthony R. Mato, MD, MSCE: Alexey or Michael, anything to add about real-world data?

Michael Wang, MD: Yes. For the oral [agents], I think the real-world data doesn't differ too much from our practice, but it's a different story if we talk (about) the CAR (chimeric antigen receptor) T-cell therapies. I think that the real-world data is very close between the two.

Transcript has been edited for clarity.