Identifying Unmet Needs in Relapsed/Refractory MCL
Insights From: Bijal D. Shah, MD, H. Lee Moffitt Cancer Center & Research Institute; Lauren C. Pinter-Brown, MD, UCI Health; Eduardo Sotomayor, MD, GW Cancer Center
Bijal D. Shah, MD: The challenge in relapsed/refractory mantle cell lymphoma is the proliferative p53-mutant cases. These patients, because of these p53 mutations, tend to be more chemotherapy refractory. These patients also tend to be more refractory to BTK [Bruton tyrosine kinase] therapy, based on what we’ve seen. And it’s not clear that agents like venetoclax will rescue this phenotype. It seems like these patients tend to fare pretty poorly, regardless of our novel agents and our chemotherapeutic approaches. And so I think really to rephrase the question, I don’t think the answer is: What do we do with relapsed/refractory mantle cell?
My opinion is: What do we do to prevent relapsed and refractory mantle cell? How do we think about combining our novel agents to, hopefully, one day prevent this proliferative relapse but at a minimum increase the length of time before that emerges? How do we think about CAR [chimeric antigen receptor] T-cell therapy as one of those novel approaches that we can integrate into our frontline therapeutic regimens, whether that be BTK based or that be lenalidomide based? How do we think about bringing in all our novel approaches to bear in mantle cell lymphoma? And I hope in following what has already happened in CLL [chronic lymphocytic leukemia] and following what has already happened in myeloma, we begin moving further and further away from chemotherapy in a disease that is divined by impaired DNA damage response.
Lauren C. Pinter-Brown, MD: In the absence of being able to cure mantle cell, which obviously I hope we could do someday, just like other—I’ll call mantle cell an indolent lymphoma, sometimes it is, sometimes it isn’t—lymphomas where we don’t have a curative intent, obviously we need the longest responses from each agent so that we can extend patients’ quality of life, progression-free-survival, and overall survival.
Eduardo Sotomayor, MD: Regarding ongoing challenges in treatment of relapsed/refractory mantle cell lymphoma, if you asked me that question 10 years ago, I would say it’s a big challenge. So right now, it is less of a challenge because we have several targeted therapies, immunotherapies, and CAR T cells. I think that the challenge is to perform a risk stratification, and do not overtreat those patients if you are going to affect their quality of life. So that’s I think the challenge for me at this time. So what should I offer to my patients these days, now that we have so many targeted agents, so many clinical trials, so many combinations? The answer is if it’s a patient with asymptomatic relapse, I may do watchful waiting or maybe a clinical trial with 2 drugs that have a good safety profile.
If it’s a symptomatic relapse, it depends whether it is a patient with bulky disease or a patient who now has a blastoid variant or has pleomorphic very aggressive mantle cell lymphoma. Definitely it’s a patient such that if he can tolerate current immunotherapies, I would be thinking about those. Sometimes having more options could present a challenge, right, because 10 years ago we didn’t have options. But I see it that way.