MCL Workshop Tackles Tough Issues Facing Rare Lymphoma Subtype

With rare diseases like mantle cell lymphoma (MCL), care providers and industry professionals must maintain strong collaboration and remain up to date on the latest breakthroughs and data. The MCL Workshop, hosted by the Lymphoma Research Foundation, is an environment for experts to do just that. Surrounding the workshop, CancerNetwork® spoke with Tycel Phillips, MD, about its impact, as well as the general MCL treatment landscape.

Phillips, a hematologist-oncologist and associate professor in the Division of Lymphoma of the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, said that MCL is unique in that it affects young and old patients, but also because its research receives more resources than other rare diseases. Many attendees enjoy seeing their colleagues from across the world at conferences like these, as did Phillips, but these meetings also result in important conversations. Phillips recalled one discussion about the treatment of patients after CAR T-cell therapy.

What is the MCL Workshop?

The MCL workshop is a biannual meeting that brings together investigators, researchers, and, in some respects, industry to discuss new, novel research, important topics/issues, and to fundamentally help us push forward with making improvements in clinical outcomes for patients afflicted with MCL. Given the rarity of MCL globally, this research venture is unique, given that typically most of the resources are invested in more prevalent malignancies, but what’s unique to MCL is the patient population, which can vary from young to sometimes very old, and also the difficulties we’ve had, which we are improving by formulating standard-of-care treatment practices for patients [experiencing] MCL. Identifying risk factors that would predispose patients to have poor outcomes to certain treatments, as well as just hope, because this [disease] could be considered somewhat of an orphan disease. Historically, [we have] obviously tried to make greater inroads to ultimately improve outcomes for our patients.

What was a highlight from the event?

Selfishly, the biggest highlight is always just the opportunity to meet other people who have a great interest and dedication to improving the lives of patients with MCL. Overall, it’s a good way to discuss and critique a lot of the recent research and get updates on a lot of important topics that are fundamentally important in day-to-day practice. One important conversation we had was specifically about outcomes post chimeric antigen receptor (CAR) T-cell therapy, and some data [were] presented that we hadn’t seen before, detailing some of the difficulties we have in managing patients in the post–CAR T-cell therapy space. That is just another area of need that has come to the forefront with the introduction of a new and effective treatment, but unfortunately, that treatment doesn’t appear to be curative for patients with MCL.

What is the role of bispecific antibodies in the lymphoma space?

As of right now, it’s still unsure. In the NCCN [guidelines], it’s a 2B designation, so you can, technically, in some cases, get it approved through insurance, but it’s not readily accessible. The bigger problem we have is that outside of academic centers, there are not a ton of centers within the US, meaning community sites, that are using bispecific antibodies, even the ones that are currently FDA approved. As of right now, it’s a niche treatment that’s mostly focused on academic sites for patients [whom] they don’t deem to be great candidates for CAR T-cell therapy, patients who don’t want to do CAR T-cell therapy, or, in some instances, as a treatment after patients relapse on CAR T-cell therapy. Hopefully, moving forward, as the bispecific antibodies as a whole get more integrated into the community setting, this will be something that could be utilized more readily across the various treatment centers within the US because the fact that it is an off-the-shelf treatment does allow a little bit more accessibility for patients vs having to relocate to a CAR T-cell center, which may or may not be close to their home. Then, given the efficacy that we’ve seen with the bispecific antibodies, you are getting comparable efficacy and durations of responses vs what we’ve seen with some of the CAR T-cell products.

What are the most pressing unmet needs in MCL?

One is patients who are high-risk. One issue that has come up is the [lack of an] accurate definition of patients with high-risk MCL. That is a focus moving forward that will be tackled sooner rather than later: to get a universal definition of what is considered high risk and, thereafter, the best ways to manage these patients. If we look at most of the clinical trials that have been reported in the [past] couple of years, we see that a vast majority of the patients are responding to treatments and are having durable responses, but there is a subset of patients who, unfortunately, seem to be more difficult to treat and are not necessarily having great responses. Specifically, there are patients with blastoid or pleomorphic morphology; there are a lot of debates and discussions about the proliferation rate, and how fast the cancer cells are growing…. Additionally, we discuss P53 mutations and how they impact clinical care.

Again, having an accurate definition and then conducting more clinical research specifically focused on trying to help these patients will be important. As I mentioned before, what do you do in certain situations where we have very effective treatments, such as Bruton tyrosine kinase [BTK] inhibitors, but…these drugs fail the patient? Because when the patients unfortunately stop responding to these medications, it does present a conundrum, because historically, we’ve seen that there are very few treatments that can help patients who have lost their response to a BTK inhibitor. Outside of CAR T-cell therapy and pirtobrutinib [Jaypirca], we don’t have any other FDA-approved options. Of the two, the CAR T-cell therapy appears to [yield] a much more durable response for patients who fail a covalent BTK inhibitor. We do need more treatments to help support patients when they fail BTK inhibitors, especially those who can’t afford to or reasonably can’t get to a CAR T-cell center. We need more options available in community situations to help these patients, so we can improve their overall survival.

What else would you like to highlight?

The biggest thing that comes out of meetings like this is the importance of clinical research. The only way to fundamentally move forward in diseases such as MCL is to continue to receive support and collaboration from [pharmaceutical companies], from patients, and from the institutions that conduct clinical research. That is the key to moving things forward.

Since the COVID-19 pandemic, things have been a little bit harder as far as conducting clinical research and getting participation from other sites, so that we can have multicenter studies. That has been a difficult thing that hopefully will not be long-lasting, because it’s great to conduct research at 1 site, but to ensure that the data are replicable, it’s much better to have multiple sites participate in a clinical trial. You get a variation of investigators, and you get a variation in the patient populations to ensure that the data that [are] obtained [can be generalized] to the population. For us to continue to make inroads in treatment and improve the outcomes in patients with MCL, we do need to continue to support these clinical research projects and ventures and continue to have the collaboration that’s been so key to a lot of the changes that we’ve been able to provide to our patients in the last couple of years.