Recent Breakthroughs in Therapies for Patients With Mantle Cell Lymphoma

Tycel Phillips, MD, City of Hope National Medical Center, Duarte, California, discusses 2 recent advancements in the treatment landscape of relapsed/refractory (R/R) mantle cell lymphoma (MCL), including the use of [Bruton’s tyrosine kinase] (BTK) inhibitor pirtobrutinib, and [chimeric antigen receptor] (CAR) T-cell therapy treatment lisocabtagene maraleucel. 

Transcript: 

Hello, my name is Dr. Tycel Phillips. I am an associate professor of medicine at City of Hope National Medical Center in Duarte, California .

Oncology Learning Network: What recent advancements or breakthroughs within the treatment landscape of mantle cell lymphoma have caught your attention? How do you envision these advancements addressing the current challenges of MCL?

Excluding glofitamab, there are 2 treatments. One was recently FDA-approved as a non-covalent BTK inhibitor, called pirtobrutinib. It has shown some efficacy in the post-covalent ibrutinib tyrosine kinase inhibitor population. I'll bet the drug is probably better situated as an alternative to a covalent BTK inhibitor, due to this improved safety profile compared to what we saw before.

The other drug would be [lisocabtagene maraleucel] (liso-cel), which is another CAR T[-cell therapy] product. This one has shown quite a bit of reduction in severe grade 3 to 4 [immune effector cell-associated neurotoxicity syndrome] (ICANS). 

With brexucabtagene [autoleucel], which is a currently FDA-approved CAR T product, we have graded 3 to 4 ICANS of about 30%, which is quite high. This is reduced to around 10% for patients with liso-cel.  

Unfortunately, liso-cel doesn't have FDA approval as of yet. But, my guess is, if it does get an indication, if the data continues to show that liso-cel is almost as effective as brexucabtagene autoleucel, then that would probably be the preferred CAR T[-cell therapy] agent for patients with relapsed/refractory mantle cell lymphoma, because of the improvement in safety that it has over [brexucabtagene autoleucel] (brexu-cel).

Source: 

Phillips T, Dickinson M, Morschhauser F, et al. MCL-467 Glofitamab monotherapy induces high complete response rates in patients with heavily pretreated relapsed or refractory mantle cell lymphoma. Clinical Lymph Myel and Leuk. Published online: September 2023. doi: 10.1016/S2152-2650(23)01378-2