Acalabrutinib in patients with mantle cell lymphoma subjected to allogeneic hematopoietic cell transplantation. a phase 2 study by the Polish Lymphoma Research Group (PLRG12 trial)

This phase 2 trial evaluated the safety and efficacy of acalabrutinib used to reduce tumor burden before allogeneic hematopoietic cell transplantation (allo-HCT) and as a maintenance therapy after transplantation in patients with relapsed/refractory mantle cell lymphoma (R/R MCL). Patients were treated with acalabrutinib 100 mg BID for 3-6 months. Those achieving complete or partial response (CR, PR) were referred for allo-HCT. Acalabrutinib was restarted 30-90 days after allo-HCT and administered for the subsequent 9 months. The remaining patients continued acalabrutinib until progression or unacceptable toxicity. Out of the 28 included patients, 16 subjects (57%) responded, with CR in 14 cases (50%) and PR in 2 cases (7%). Fifteen patients (54%) underwent allo-HCT. Twenty-three patients (79%) had grade 3-4 adverse events, most commonly neutropenia (34%) and infections (21%). Five patients died of treatment-related toxicity, including infections in 4 cases. he probabilities of overall and progression-free survival (PFS) at 2 years were 60% (95%CI, 40-79) and 41.5% (23-60), respectively. PFS rate for patients treated with allo-HCT was 67% (44-92) at 18 months. Acalabrutinib generates high response rates in patients with R/R MCL and may serve as a "bridge" to allo-HCT and maintenance after transplantation. Infections are most frequent life-threatening complications.