Selecting the Appropriate Treatment in R/R MZL

Tycel Jovelle Phillips, MD: Dr Danilov, what do you consider when selecting therapy for relapsed/refractory marginal zone lymphoma in the second line and beyond? How do you choose which agent you use in this situation, whether it be chemotherapy or some of these more novel agents?

Alexey Danilov, MD, PhD: It really becomes very individualized. Marginal zone lymphoma is a rare disease, and we will not have a whole lot of head-to-head comparison. In fact, what we have is already very helpful. We choose between IV [intravenous] versus oral formulation. Intermittent dosing with drugs like copanlisib, if patients can reliably come to the infusion room, can be attractive. And then, of course, there is a question of efficacy and toxicity based on patients’ comorbidities. Ultimately, it becomes an individualized decision, what prior therapies patients have received, and what efficacy they have achieved already.

Tycel Jovelle Phillips, MD: That’s a very good way to summarize this situation and some of the complex conversations we have with our patients in the clinic. Overall, having a multitude of options is very important, whether it be the BTK [Bruton tyrosine kinase] inhibitors with zanubrutinib and ibrutinib, and what they bring to our armamentarium. Or even the delta inhibitors ideally, because of some of the things that they have, obviously with a different toxicity profile for what we see with BTK inhibitors or even what we see with R² [lenalidomide and rituximab] in chemoimmunotherapy. Having this class of drugs gives us an option to offer patients different sorts of treatments. And it’s been my experience that delta inhibitors, at least we know that when patients respond, they tend to respond very quickly, with most responses to delta inhibitors occurring within the first 1 to 2 months after initiation of therapy. If they are going to work, we’ll know very early on, versus some of these other treatments, which sometimes have a slower onset of efficacy given the different mechanisms of action.

Ideally, some of the adverse effects that you’ve highlighted are things that we know, and we have to keep a very close eye on. Obviously, transaminitis is an issue that can occur very early in some of our patients, especially with some of the delta inhibitors that are FDA approved. Diarrhea is something that we must keep a very close eye on. There are generally 2 types of diarrhea: the early onset diarrhea that won’t necessarily cause our patients to come off study and is generally not associated with colitis, and the later onset diarrhea, which is thought to be more immune-mediated and is generally the diarrhea and colitis that typically causes drug discontinuation. Inflammation of the lungs, such as pneumonitis, is something important that we have to keep an eye on, also rash and blood counts.

But with more experience and the more time we have with these agents, we are able to mitigate and assuage some of these AEs [adverse events] to the point to allow our patients to obtain the maximum benefit that comes from these drugs without necessarily exposing them to any undue adverse events and toxicity. Moving forward with more of these PI3 kinase delta inhibitors, especially some of the second-generation ones and the utilization of the intermittent schedule as you mentioned earlier, will be very helpful for allowing us to continue to use these drugs and provide another effective option for our patients.

Transcript Edited for Clarity