Phase II Trial Finds Acalabrutinib/Lenalidomide/Rituximab Triplet Safe, Effective Against MCL

The triple chemotherapy-free combination of acalabrutinib, lenalidomide, and rituximab is well tolerated, highly effective, and produces high rates of minimal residual disease (MRD)-negative complete remission (CR) as initial treatment for mantle cell lymphoma (MCL), including high-risk patients with TP53 mutations.

Preliminary findings are from a phase II trial and were presented in an oral presentation at the 2022 American Society of Hematology Annual Meeting by Jia Ruan, MD, PhD, of Weill Cornell Medicine and New York Presbyterian Hospital in New York, and colleagues.

The ongoing study includes induction and maintenance, with acalabrutinib provided at 100 mg twice daily continuously. Lenalidomide is administered at 15 mg daily on days one through 21 of a 28-day cycle for 12 cycles during induction, with dose escalation to 20 mg if tolerated, then dose reduction to 15 mg during maintenance. Rituximab is administered weekly four times during cycle one, then once every other cycle throughout induction and maintenance.

The study enrolled 24 subjects between October 2019 and October 2021. At study entry, median age was 64 years (range, 35-77 years), and the male to female ratio was 3.8:1. All patients had stage III/IV disease, 21% had elevated lactate dehydrogenase, and 96% had bone marrow involvement. TP53 mutations were detected in 29% of subjects.

As of July 2022, at a median follow-up of 19 months, all 24 patients (100%) remain on the study without evidence of progression, including 21 who have completed 12 cycles of induction; 11 patients completed 24 cycles of treatment. Of the 21 patients evaluable for the primary endpoint, the overall response rate was 100% (90% CI, 87-100), and the CR rate was 90.5% (90% CI, 73-98) after 12 cycles of treatment. Peripheral blood MRD was undetectable (<10^-6) in 50% of patients (n=12/24) after six cycles, 71% (n=15/21) after 12 cycles, and 82% (n=9/ 11) after 24 cycles, including 80% patients (n=4/5) with TP53 mutations achieving MRD-negative CR after 12 cycles.

The treatment was well tolerated with expected side effects, according to the investigators.

Reference

Ruan J, Leonard J, Chen G, et al. Phase 2 trial of acalabrutinib-lenalidomide-rituximab (ALR) with real-time monitoring of MRD in patients with treatment-naïve mantle cell lymphoma. Abstract #73. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.