Dr Phillips on Research Directions Beyond BTK Inhibition in Mantle Cell Lymphoma

“It would be nice to see a large, randomized study comparing BTK inhibitor–based frontline regimens to [other treatment options].”

Tycel Phillips, MD, an associate professor in the Department of Hematology and Hematopoietic Cell Transplantation in the Division of Lymphoma at City of Hope, discussed the next steps researchers should take in terms of investigating novel classes of agents beyond BTK inhibitors in mantle cell lymphoma (MCL) and the design of future clinical trials.

Phillips began by underscoring the prevalence of BTK inhibitors in the MCL treatment paradigm. Ultimately, seeing how these agents stack up against other treatments in large, randomized trials might be of use for the MCL field, he said. Phillips specifically pointed out acalabrutinib (Calquence) plus bendamustine and rituximab (Rituxan; BR), which was approved by the FDA in January 2025 for patients with previously untreated MCL who are ineligible for autologous hematopoietic stem cell transplantation, as a BTK inhibitor–based regimen that he wants to see evaluated against other treatment options.

The approval of the combination was supported by data from the phase 3 ECHO study (NCT02972840). Regarding efficacy, at a median follow-up of 49.8 months, results from the trial showed a median progression-free survival of 66.4 months (95% CI, 55.1-not estimable [NE]) for patients who received the combination (n = 299) compared with 49.6 months (95% CI, 36.0-64.1) for patients who received a placebo (n = 299; HR, 0.73; 95% CI, 0.57-0.94; P = .016).

Phillips then noted how large, randomized studies comparing BTK inhibitor–based regimens to others in the first-line setting might provide crucial insight on how much the use of early BTK inhibition impacts remission durations for patients. However, the size of larger trials might be more difficult within the MCL field compared with other more commone lymphoma subsets like large cell lymphoma, Phillips added.

Despite these challenges, Phillips explained that there will likely be a plethora of studies looking at numerous first-line MCL treatment options.