The multitargeted CARiBOU regimen elicited complete metabolic responses (CMRs) in patients with previously untreated mantle cell lymphoma (MCL), according to phase 2 data from the ACCRU-LY-1804 trial (NCT04626791) published in the American Journal of Hematology.1
Among 41 patients evaluated by intention to treat, the regimen, which alternates VR-CAP with rituximab (Rituxan) plus cytarabine and adds continuous acalabrutinib (Calquence), generated a CMR rate of 90% (95% CI, 83%-99%) and an objective response rate (ORR) of 95% (95% CI, 92%-100%). Undetectable measurable residual disease (MRD) at a threshold of 10-6 was achieved 79% of evaluable patients (n = 33) at the end of treatment, and 94% reached MRD negativity at the 10-5 threshold. At a median follow-up of 17 months, the estimated 18-month progression-free survival (PFS) rate was 79% (95% CI, 64%-97%) and the 18-month overall survival (OS) rate was 96% (95% CI, 88%-100%).
“CARiBOU is an efficient, highly effective outpatient [first]-line MCL regimen, employing intermediate-dose cytarabine and continuous acalabrutinib for 6 cycles,” lead study author Stephen D. Smith, MD, of Fred Hutchinson Cancer Center and the University of Washington School of Medicine in Seattle, and colleagues wrote in the publication. “This multitargeted regimen addresses the biologic heterogeneity of MCL and permits flexible MRD-guided decisions on consolidation and maintenance.”
CARiBOU (ACCRU-LY-1804) was a single-arm, multicenter phase 2 trial conducted across 4 centers in the Academic and Community Cancer Research United network. Eligible patients were at least 18 years of age, had no prior systemic therapy for MCL, and were considered eligible for autologous stem cell transplantation (ASCT) by investigator judgment, with an ECOG performance status of 2 or less.
The regimen consisted of six 21-day cycles alternating VR-CAP—bortezomib (Velcade), rituximab, cyclophosphamide, doxorubicin, and prednisone—in cycles 1, 3, and 5 with rituximab plus cytarabine in cycles 2, 4, and 6, along with continuous acalabrutinib at 100 mg twice daily.
The primary end point was CMR rate.
The trial accrued 41 patients between October 2021 and June 2025. The median age was 61 years (range, 41-73), 78% of patients were male, and MCL International Prognostic Index risk was intermediate or high in 56% of patients. Elevated Ki-67 (≥30%) was present in 54% of patients, and TP53 mutations were detected in 12% of tested patients (n = 34).
After thrombocytopenia was observed in the first 5 patients, the cytarabine dose was reduced from 3 g/m² to 2 g/m² given as two daily doses for all subsequent patients. Other frontline MCL regimens integrating BTK inhibition with intensive chemoimmunotherapy have also generated high response rates, including zanubrutinib (Brukinsa) plus rituximab, bendamustine, and cytarabine in treatment-naive disease.2
Thirty-seven of 41 patients achieved a CMR; the 2 nonresponders discontinued therapy for toxicity before study-defined restaging and received alternate treatment.
Among 34 patients who underwent bone marrow assessment at the end of treatment, 32 (94%) were negative for MCL. Among the 4 patients with baseline TP53 mutations, 1 discontinued early due to toxicity, whereas the other 3 achieved a complete response with undetectable MRD at 10-6 and none had relapsed during follow-up.
Because consolidation and maintenance were not protocol-defined and treatment practices shifted during the study, only 9 patients (23%) underwent ASCT, with no stem cell collection failures.
Rituximab maintenance was administered to 92% of patients who completed therapy, and BTK inhibitor maintenance was used in 23%. Four patients had relapsed at data cutoff, and 2 deaths occurred—one from COVID-19 complications and one from progressive MYC-rearranged disease.
Toxicity was primarily hematologic. Grade 3 or higher hematologic adverse effects (AEs) occurred in 32 patients (78%), including thrombocytopenia in 66%, neutropenia in 29%, and anemia in 27%; grade 4 thrombocytopenia was reported in 55% of patients. Febrile neutropenia occurred in 4 patients (10%), grade 3 nonhematologic AEs were reported in 13 patients (32%), and 6 patients (14%) experienced serious AEs, primarily febrile neutropenia or infection. No treatment-related deaths occurred during or within 100 days of study therapy.
Platelet transfusions were required exclusively during cytarabine nadirs, in 12 of 41 patients (29%). The cytarabine dose reduction lowered the proportion of cycles requiring transfusion support from 60% at 3 g/m² to 9% at 2 g/m². With twice-weekly blood count monitoring, clinically significant bleeding was uncommon, with a single grade 3 gastrointestinal bleed occurring in a patient with a newly diagnosed duodenal ulcer. One grade 3 atrial fibrillation event was observed, with no ventricular arrhythmias.
