<p>CAR T-cell therapy is a promising alternative to standard treatments for patients with relapsed/refractory mantle cell lymphoma (MCL) and may help extend survival in those who would otherwise have limited treatment options. However, some patients may not tolerate this treatment or may not have the social support that is required, so careful patient evaluation is important.</p>

Many factors need to be taken into consideration when choosing therapies for our patients with MCL. Patients who are a bit older, which is sometimes the case with MCL, might not be able to tolerate some of our more aggressive treatments. We also need to consider which induction and salvage therapies the patient has already had, as well as any health comorbidities they may have.

 

If a patient has failed on standard immunochemotherapy, an anti-CD20 antibody, and a BTK inhibitor, then there are not a lot of good options left for that individual. You may try different combinations of standard therapies or different treatment options such as venetoclax or a noncovalent BTK inhibitor. Pirtobrutinib is the only US Food and Drug Administration (FDA)–approved noncovalent BTK inhibitor, and it is typically used when a patient has failed to respond to or cannot tolerate a covalent BTK inhibitor. I definitely consider pirtobrutinib if a patient is not a candidate for CAR T-cell therapy.

 

CAR T-cell therapy would probably be at the top of my list for patients with MCL who have failed chemotherapy, an anti-CD20 monoclonal antibody, and a BTK inhibitor. This is assuming that they meet other criteria, including having good organ and cardiac function, being in otherwise good health, and being able to tolerate potential side effects. We evaluate patients extensively to make sure that they are candidates for CAR T-cell therapy before starting treatment.

 

If the patient is a candidate, we first need to be certain that they have the social support they need to be able to receive CAR T-cell therapy in the outpatient setting, as this therapy requires that patients have a lot of assistance from family members or caregivers. Patients are monitored very carefully for any adverse effects from the treatment for 28 days after CAR T-cell infusion. They have to have a caregiver with them 24/7 during that 28-day period, and that is the part that is sometimes difficult.

 

It is good to have the option of different CAR T cells for our patients. In the ZUMA-2 study, the response rate to brexucabtagene autoleucel (brexu-cel) was quite high. As time goes on, we are seeing that some patients on brexu-cel therapy are relapsing, especially higher-risk patients who perhaps have a high Ki-67 proliferation index, TP53 abnormalities, or a complex karyotype. Lisocabtagene maraleucel (liso-cel) also has very high response rates and seems to have slightly less toxicity associated with it than brexu-cel, especially less high-grade immune effector cell–associated neurotoxicity syndrome and cytokine release syndrome. So, I think that liso-cel may be an appropriate choice, especially for older patients with more comorbidities.