Outcomes From the Multicenter ACCRU-LY-1804/CARiBOU TRIAL (Cytarabine, Acalabrutinib and Rituximab Integrated With...

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 10⁶ threshold was achieved in 26/33 tested patients (79%), and 94% at 10⁵. 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.