A prospective, multi-center, phase IV clinical study to assess the safety and clinical outcome of acalabrutinib in Indian adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma or relapsed/refractory mantle cell lymphoma.

OBJECTIVE: To evaluate the safety and clinical outcomes of acalabrutinib in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or refractory/relapsed mantle cell lymphoma (MCL) in a real-world setting in India. METHODS: This Phase IV, open-label, single-arm, multi-center, prospective study included 89 patients with CLL/SLL (treatment naive or one or more prior therapy) and 11 patients with refractory/relapsed MCL who received acalabrutinib capsules 100 mg orally twice daily for six 28-day cycles or until study drug discontinuation. Patients were followed up for 28 days after the drug discontinuation to collect additional safety data. The primary endpoint was the incidence of adverse events (AEs), treatment-emergent AEs (TEAEs), serious adverse events (SAEs), second primary malignancies, and other AEs of clinical interest. Secondary endpoints included objective response rate (ORR) and quality of life. RESULTS: By the end of the follow-up period, 48 (54%) patients in the CLL/SLL cohort and 9 (82%) patients in the MCL cohort reported at least one AE. Of these, 38 (43%) patients in the CLL/SLL cohort and 7 (64%) in the MCL cohort reported TEAEs, with serious TEAEs reported in 9% and 27%, respectively. Three patients in CLL/SLL and two in MCL reported drug-related TEAEs. Drug-related deaths were reported in two MCL patients. Drug discontinuation due to AEs was reported in 3.4% and 18.2% of the CLL/SLL and MCL cohorts, respectively. During the follow-up period, the ORR was 62% in CLL/SLL cohort and 36% in MCL cohort, with quality of life scores maintained throughout. CONCLUSION: The study demonstrated safety of Acalabrutinib with no new signals and encouraging clinical outcomes in Indian patients with CLL/SLL and MCL, consistent with global clinical trials. CLINICALTRIALSGOV IDENTIFIER: NCT04930536.