Dr Kahl on Future Directions for Frontline Treatment Strategies in MCL

“These data suggest that if you add a BTK inhibitor to the induction, you don’t need the high-dose cytarabine… What to do in high-risk disease, whether high-dose cytarabine is needed, and whether chemotherapy-free approaches can replace chemotherapy [are remaining questions in MCL].”

Brad S. Kahl, MD, a professor of medicine in the Division of Oncology and director of the Lymphoma Program at Washington University School of Medicine, discussed remaining questions surrounding frontline treatment approaches in mantle cell lymphoma (MCL).

With the role of autologous stem cell transplantation becoming clearer, Kahl said his attention in MCL is shifting toward other topics. Kahl noted the phase 3 TRIANGLE trial (NCT02858258) and its incorporation of high-dose cytarabine but questioned whether cytarabine remains necessary.

He pointed to the phase 2 ECOG-ACRIN EA4181 trial (NCT04115631), which compared chemotherapy regimens that included a BTK inhibitor. According to Kahl, findings from the trial suggest that adding a BTK inhibitor may permit the omission of high-dose cytarabine from induction.

Another priority in MCL is improving treatment for patients with high-risk MCL, including disease harboring TP53 mutations, Kahl noted. High-risk MCl tends to respond poorly to chemotherapy, he explained. Emerging chemotherapy-free combinations composed entirely of targeted agents have generated improved outcomes, but additional investigation is needed, Kahl added.

According to Kahl, the success of targeted approaches in high-risk disease raises a broader question: Could chemotherapy-free regimens also improve outcomes for patients without high-risk MCL? A forthcoming study is expected to compare standard immunochemotherapy with a chemotherapy-free strategy, he highlighted. Collectively, Kahk concluded that these efforts are evaluating whether clinicians can reduce cytarabine exposure, individualize therapy for high-risk disease, and eventually remove chemotherapy from frontline MCL treatment.