“Promising” Approaches May Advance Mantle Cell Lymphoma Therapy

In a visit to Yale Cancer Center in New Haven, Connecticut, CancerNetwork® spoke with Shalin Kothari, MD, about ongoing research initiatives that show promise in improving the care of patients with mantle cell lymphoma (MCL).

According to Kothari, an assistant professor of medicine (hematology) at Yale University, a potentially notable strategy is achieving coinhibition by administering BCL2 inhibitors with Bruton tyrosine kinase (BTK) inhibitors, with studies like the phase 3 SYMPATICO trial (NCT03112174) demonstrating an improvement in responses through this combinatorial approach. He also highlighted the promise of drug classes like noncovalent BTK inhibitors, MALT1 inhibitors, and chimeric antigen receptor (CAR) T-cell therapies in MCL. Regarding T-cell therapies, specifically, Kothari emphasized studying how to reduce manufacturing times to help reduce the likelihood of clinical progression among patients.

Transcript:

There are [many] promising approaches. No. 1 would be the combination of adding a BCL2 inhibitor and combining it with BTK inhibitors; like coinhibition. The trial that studied that [strategy] is the SYMPATICO trial [NCT03112174], where there was improvement in the complete response rate and overall response rate. That’s something that I would consider in the relapsed/refractory setting.

There are many other promising approaches. We can talk about noncovalent BTK inhibitors like pirtobrutinib [Jaypirca]. There are drugs like BTK degraders, which, rather than inhibiting, they degrade the BTK protein. That’s a promising approach. In addition, we have other novel drugs such as MALT1 inhibition or even CAR T-cell therapy. There are 2 CAR T-cell therapies that are already approved. There are many more products being studied, especially to figure out ways to reduce the manufacturing time.

Right now, the current CAR T-cell therapies take around 4 to 5 weeks to manufacture. If the patients are experiencing significant progression, then that is a long enough time that they can have clinical progression, which could be clinically meaningful within the 4- to 5-week period. Reducing the manufacturing time has a big impact. There is research going on in all directions.

Reference

Wang M, Jurczak W, Trneny M, et al. Ibrutinib plus venetoclax in relapsed or refractory mantle cell lymphoma (SYMPATICO): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2025;26(2):200-213. doi:10.1016/S1470-2045(24)00682-X