Alternatives to CAR T-Cell Therapy Needed Post-BTK Inhibitor in R/R MCL

Tycel Phillips, MD, a clinical associate professor of hematology and medical oncology at the University of Michigan, discusses the need for more effective agents for treating patients with relapsed/refractory mantle cell lymphoma (R/R MCL) as alternatives to chimeric antigen receptor (CAR) T-cell therapy.

According to Phillips, the only therapy with significant efficacy for patients with R/R MCL who have failed to benefit from Bruton tyrosine kinase (BTK) inhibitors is brexucabtagene autoleucel (Tecartus), a CAR T-cell therapy. Other agents, including venetoclax (Venclexta), lenalidomide (Revlimid), and PI3 kinase inhibitors such as idelalisib (Zydelig), have not been effective in this setting. One option that may offer benefit for these patients is bendamustine and cytarabine, but many patients have already received these agents before BTK inhibitors.

Phillips notes that in Michigan, only 3 centers offer CAR T-cell therapy for MCL, all in the southeast part of the state, leaving many patients without easy access to treatment. Patients would need to travel long distances or be separated from their families to receive infusions, leading many patients to avoid treatment.

Therefore, he says there is a serious unmet need for new therapies that can be given post-BTK inhibitors without requiring patients to go outside their community. Phillips is currently investigating the bispecific antibody glofitamab, which shows potential efficacy in this setting.

TRANSCRIPTION:

0:08 | As of right now, the only real agent we have that has shown any demonstrable efficacy in this R/R MCL population post BTK inhibitors has been the CAR T product from [Kite Pharma]. As for agents that we've explored—venetoclax, lenalidomide, the PI3 kinase inhibitors all have shown to be very ineffective in this patient population. There is a retrospective study that has demonstrated that bendamustine and cytarabine appears to be effective, but a lot of these patients will have already seen bendamustine. And a lot of them will already receive cytarabine by the time they fail the BTK inhibitor.

Based on the limited availability of CAR T products to most patients, again, because even in our state, there are only select centers…3 sites within the state that can actually administer this treatment. And they're all for the most part saturated in the southeast corner of Michigan. There's a whole swath of our state that's not necessarily within close proximity to a CAR T center. So again, CAR T is still at this point limited for most patients because of selectivity to where they live in relation to a CAR T center.

1:22 | A lot of these patients don't have access to a readily-accessible treatment option post BTK inhibitors. A lot of these patients, they can't get to a CAR T center, or they don't want to necessarily be separated from their families, they don't have a lot of great options and will succumb to their disease. So, the post BTK R/R MCL patient is still a patient that has a very high need for new and novel treatments and even more treatment that can actually be given in the community and don't necessarily require being treated at a select center.