Dr Mead on Unanswered Questions in the Treatment of MCL

Monica D. Mead, MD, assistant clinical professor, medicine, the University of California, Los Angeles (UCLA), UCLA Health, UCLA Jonsson Comprehensive Cancer Center, discusses the importance of addressing unanswered questions in the treatment of patients with mantle cell lymphoma (MCL).

There are many important unanswered questions within the MCL treatment landscape, Mead begins. The phase 3 TRIANGLE trial (NCT02858258) evaluated the combination of ibrutinib (Imbruvica) and standard induction chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) and fixed 2-year maintenance, Mead explains. Induction therapy consisted of R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone)/R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin).

After a median follow-up of 31 months, ASCT alone did not produce superior failure-free survival (FFS) vs ibrutinib alone, whereas ibrutinib and ASCT elicited a higher FFS compared with ASCT alone. Based on these data, the authors concluded that sufficient efficacy is seen with the addition of a BTK inhibitor to conventional chemotherapy in the frontline setting, Mead emphasizes. However, the the role of transplantation in the frontline setting has yet to be confirmed, she adds. Therefore, longer follow-up data from the TRIANGLE study could elucidate whethersequencing ASCT prior to treatment with rituximab and BTK inhibitor maintenance provides superior benefit vsproceeding to maintenance therapy in the absence of a transplant, Mead says.

Another pressing question in the field of MCL is how to optimally manage patients with MCLdisplaying TP53 mutations, Mead continues. This is considered a particularly challenging patient subset to treat, Mead notes. Studies utilizing various agents have shown decreased efficacy in the TP53-mutant patient population, Mead highlights. It remains important to understand how other MCL-directed agents perform in this patient subset.Several ongoing clinical trials in this space aim to develop more creative treatment strategies for this difficult-to-treat population, Mead concludes.