As initial treatment, most younger patients with MCL receive a cytarabine-containing induction regimen followed by autologous stem cell transplantation (ASCT). The treatment approach for relapsed disease is tailored to each individual patient and to the aggressiveness of the MCL. Although there is no standard approach to the treatment of those with MCL who relapse following intensive induction therapy, we have many options for these individuals, and we must take patient and disease characteristics into consideration when determining the best approach to sequencing these therapies. We first look at the treatment that the patients received previously (eg, how did they do on Bruton tyrosine kinase [BTK] inhibitors?). After that, we can consider the different options, including lenalidomide and other combinations; even allogeneic SCT would be an option for younger patients. 

If the patient relapses after the induction regimen and ASCT, I would argue that a BTK inhibitor would be the standard of care. Several different BTK inhibitors are currently available (ie, ibrutinib, acalabrutinib, and zanubrutinib). So, I would consider the toxicity profiles of those agents, the disease characteristics, and the patient characteristics and comorbidities when selecting a treatment. Chimeric antigen receptor (CAR) T-cell therapy is now an option for those with relapsed MCL. Prior to CAR T-cell therapy, patients typically would have already been treated with a cytarabine-containing induction chemoimmunotherapy with rituximab, ASCT, a BTK inhibitor, and, perhaps, an immunomodulatory drug.

Patients with aggressive MCL and the TP53 mutation are very difficult to treat. They usually respond very briefly or not at all to frontline chemoimmunotherapy. Some of these individuals do achieve a brief remission with BTK inhibitors. And we certainly consider CAR T-cell therapy for such patients. So, while there are not as many options for these patients, we do have some good therapies available.

Regarding clinical trial participation, for low-risk patients with MCL who require treatment, we would likely go through the treatment algorithm with induction therapy, possibly transplantation, and a BTK inhibitor. After that would be a good time to either start CAR T-cell therapy or consider clinical trials. For higher-risk patients, we tend to consider clinical trials a bit sooner because the standard-care therapies do not work very well. There are several clinical trials of interest, including those that combine BTK inhibition with CAR T-cell therapy.