How to Move the Needle in Defining High-Risk MCL?

The Lymphoma Research Foundation (LRF) hosts the annual Mantle Cell Lymphoma (MCL) Scientific Workshop, which is a global scientific meeting promoting collaboration and resource sharing among researchers dedicated to this rare lymphoma subtype.

Kami J. Maddocks, MD, who participated in the 2025 meeting, noted the inherent challenges of studying MCL because of the small number of affected patients. Collaborations fostered by the workshop are crucial to conducting practice-changing clinical trials and research that would be difficult to execute at a single center. Furthermore, this collaborative approach is essential for establishing the best therapies, end points, and pathways for securing drug approvals from regulatory bodies such as the FDA and European Medicines Agency (EMA), she said.

A particular focus at the meeting was high-risk MCL. Patients with TP53 mutations, blastoid disease, and high Ki-67 generally have inferior outcomes with standard treatment regimens. Consequently, a working group is being formed to better define this high-risk population, particularly to ensure a similar patient cohort for clinical trial eligibility moving forward.

Maddocks is a clinical professor in the Division of Hematology at The Ohio State University in Columbus and medical director of infusion services at The James Comprehensive Cancer Center.

What is the background of the MCL Workshop?

The MCL Workshop comes out of the [Lymphoma Research Foundation], [which began approximately] 20 years ago. The LRF recognized the need to have dedicated investigators come together to discuss this rare subtype of lymphoma, and as this group grew, so did interest, and more people wanted to meet with the group. They formally established the consortium and formed this annual meeting, which is now a global scientific workshop to promote collaboration and sharing of resources among researchers around the world.

What was a highlight from the 2025 event?

The whole event was a highlight, but we had about 100 consortium members and invited speakers. One of the highlights was just the great discussions that we had, in addition to the research and the information, the talks that were presented. There was so much discussion and excitement regarding what was going on in the field and how we could collaborate to move things forward.

Another highlight for me was a good discussion on high MCL and how we can better characterize this for clinical trial eligibility, better define this high-risk patient population. [We want to conduct] clinical trials that have these patients included, and…better study therapies for this population, because [they] have worse outcomes or inferior outcomes to our standard therapies at this time. Moving forward, we are forming a working group to work on defining high-risk MCL.

What is the importance of this meeting?

MCL is a rare subtype of lymphoma, and it can be challenging to study because of the smaller number of patients affected by this disease. It’s important that we come together to share our ideas about preclinical work that is ongoing, and that we work together on clinical trials, because it’s very difficult to conduct a clinical trial at a single center. We have to utilize our collaborations to do practice-changing clinical trials and practice-changing research as a community. To be able to get drugs approved through the FDA and the EMA for patients with MCL, it’s important for us to be able to collaborate, understand the best therapies, the best end points, and the best path forward for drug approvals.

What are some of the most pressing needs in MCL that current clinical trials are aiming to address?

In patients with the high-risk disease, particularly patients with TP53 mutations, but also patients with blastoid disease, high Ki-67, other mutations, and complex karyotypes, all have been shown to have inferior outcomes to our standard treatment regimens. Defining this population and finding improved frontline therapies [is imperative]. Historically, we’ve used intensive chemotherapy, chemoimmunotherapy, and autologous stem cell transplant, and as we have the availability of targeted therapies, moving our frontline therapy to more targeted therapies with improved toxicity profiles for patients is important. Regarding relapse in MCL, as we move BTK [Bruton tyrosine kinase] inhibitors into frontline therapy, there is a need for improved therapies in the relapse/refractory setting, including in patients who either have progressed or who don’t have access to or are not able to get CAR [chimeric antigen receptor] T-cell therapy. These are all unmet needs in this disease.

How do you see the treatment landscape evolving?

I hope that we can eliminate the use of chemotherapy in the frontline setting for patients. We have very effective targeted cellular antibody therapies, and my hope is that, for diseases like MCL, we can find ways so that most patients are not being exposed to chemoimmunotherapy in the frontline setting. This requires us to be able to find even better targeted therapies and cellular immunotherapies when they progress after the initial ones.

Is there anything else you’d like to highlight?

One of the things that came out of the workshop is that we will be forming an international working group to better discuss and define the high-risk population, particularly for clinical trial eligibility, as we move forward.