Emerging Strategies for Mantle Cell Lymphoma Treatment

Treatment of relapsed mantle cell lymphoma (MCL) can be challenging due to patents’ rapid development of chemotherapy resistance; however, recent developments in MCL are increasingly moving toward novel approaches that are resulting in improved outcomes.

In this exclusive video, Manali Kamdar, MD, of the University of Colorado Cancer Center in Aurora, provides an overview of the current treatments in MCL, and outlines some emerging therapeutic strategies for this disease that were presented at the recent American Society of Hematology (ASH) annual meeting.

Following is a transcript of her remarks:

Mantle cell lymphoma has really undergone a sea change compared to where we were prior to the advent of targeted therapies. Previously, all we had in our armamentarium was chemotherapy, auto-transplant, and allo-transplant. I think at this point in time the field is certainly blessed because we have at least two other lines of treatment that we can offer our patients with mantle cell lymphoma.

So currently, I think especially for patients who relapsed for the first time, so after they have been exposed to one line of treatment, what we do have that’s FDA approved are Bruton tyrosine kinase [BTK] inhibitors. We have the first- and second-generation [BTK inhibitors] — meaning ibrutinib [Imbruvica], acalabrutinib [Calquence], and zanubrutinib [Brukinsa] — approved for patients with relapsed/refractory mantle cell lymphoma. These patients fortunately do have a good response — median responses of at least 66% with the CR [complete response] rate of about 20% to 30% based on which trial you look at. And then the most recent FDA approval came in the way of brexucabtagene (Tecartus), so CAR T-cell therapy for these patients as well.

However, for BTK inhibitors, the one issue that we do run into is the fact that these patients get therapy indefinitely. And number two, for high-risk mantle cell lymphomas, such as blastoid, pleomorphic, or TP53-aberrant mantle cell lymphoma, although the response rate may be similar, the median duration of response is shorter than patients who do not express these adverse risk factors. And I think this is what we did see overcome with the CAR T-cell therapy data. There was a follow-up that was presented, and the follow-up actually looks very promising — patients who ended up with a complete response continue to have that response even at the 2-year mark.

However, as we all know, CAR T-cell therapy is not for all. We definitely are looking for more other constructs and the data. For example, there is lisocabtagene [Breyanzi] that is also being looked at in patients with relapsed/refractory mantle cell lymphoma. And in terms of the efficacy, I believe they may be comparable. But in terms of safety, based on the fact that it’s a 4-1BB construct, the safety may be slightly better as compared to the CD28 construct.

And then, again the same question as to what after CAR-T? We do have patients who do relapse after CAR T-cell therapy. And I think in those patients there may be more hope coming around the way for patients who fail BTK inhibition, people who fail CAR T-cell therapy. So we now have the [recently approved] reversible BTK inhibitor, which was LOXO305 now called pirtobrutinib [Jaypirca], which showed some really good responses in relapsed/refractory mantle cell lymphoma. That data was presented by Dr. Wang and colleagues at ASH 2022, was very impressive.

And then my colleague Dr. Tycel Phillips presented excellent data about bispecific-antibody treatment with glofitamab in patients with relapsed/refractory mantle cell lymphoma. I think that data also certainly looked very good, because it showed responses in patients who had failed Bruton tyrosine kinase inhibitors as well.

So again, the field is looking very good, and we look forward to many, many more novel constructs that continue to be explored in this subtype of lymphoma.