Outcomes From the Multicenter <scp>ACCRU</scp> ‐ <scp>LY</scp> ‐1804/ <scp>CARiBOU TRIAL</scp> (Cytarabine, Acalabrutinib and Rituximab Integrated With Bortezomib‐Based Outpatient Therapy) in 1st Line Mantle Cell Lymphoma

ABSTRACT First‐line therapy for mantle cell lymphoma (MCL) represents a critical opportunity for clinical benefit via sustained complete response. We conducted a phase 2 multicenter trial in the academic and community cancer research united (ACCRU) network, testing a multitargeted 1st line regimen. CARiBOU (ACCRU‐LY‐1804) employs alternating VR‐CAP and R‐cytarabine with continuous acalabrutinib, in six 21‐day cycles, for previously untreated MCL. The primary endpoint was complete metabolic response (CMR) rate. Secondary endpoints included safety, feasibility of stem cell collection, proportion proceeding to ASCT, and progression‐free (PFS) and overall survival (OS). Peripheral blood measurable residual disease (MRD) was tested using the ClonoSEQ assay (Adaptive Biotechnologies). Of 41 patients enrolled, 39 (95%) responded to therapy, including 37 patients achieving CMR (90%). Two nonresponders discontinued therapy for toxicity early, prior to study‐defined restaging, and received alternate therapy. Undetectable MRD at a 10 6 threshold was achieved in 26/33 tested patients (79%), and 94% at 10 5 . 18‐month estimated PFS is 79% (95% CI 64%–97%), and OS is 96% (95% CI 88%–100%). Toxicities were primarily hematologic (grade 3 hematologic AE in 32 patients, [78%]). Twelve required platelet transfusions, and one grade 3 bleeding event occurred. Febrile neutropenia occurred in 4 patients, and 6 (14%) experienced SAEs. There were no treatment‐related deaths. CARiBOU is an efficient, highly effective outpatient 1st line MCL regimen, employing intermediate‐dose cytarabine and continuous acalabrutinib for 6 cycles. This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD‐guided decisions on consolidation and maintenance. Trial Registration: ClinicalTrials.gov identifier: NCT04626791