Acalabrutinib, an irreversible selective BTK inhibitor, has demonstrated clinical efficacy in relapsed chronic lymphocytic leukemia (CLL). Preliminary data from an ongoing phase 1/2 study of acalabrutinib in 72 patients with previously untreated CLL show clinical activity at both dose schedules (100 mg twice daily, 200 mg once daily) that were tested. All patients experienced rapid reduction in lymphadenopathy. Treatment-related lymphocytosis occurred in 53% and resolved in 97% of these patients. The overall response rate was 96%, with median time to response of 2 months. Neither CLL progression nor Richter’s transformation has occurred to date. A phase 3 trial comparing acalabrutinib with ibrutinib in relapsed CLL is underway.
Two-year data are now available from the international, double-blind, placebo-controlled, phase 3 study (HELIOS) comparing ibrutinib + bendamustine and rituximab (I+BR) and placebo + BR (BR) in patients with previously treated CLL/small lymphocytic lymphoma (SLL). At the first analysis (median follow-up, 17 months), progression-free survival (PFS) was significantly improved for I+BR versus BR. After 25.4 months, I+BR continues to show improvement in PFS (median not reached vs 14.2 months [BR]). Median overall survival is not yet reached in either arm. Rates of minimal residual disease (MRD)-negative response in the intent-to-treat population are 18% (I+BR) and 5% (BR). No new or unexpected safety signals are reported in this update.
GREEN is an ongoing phase 3b, open-label trial of OBIN alone or with chemotherapy in patients with previously untreated or relapsed/refractory CLL. The primary outcome is safety. In the study, patients receive OBIN alone or with chemotherapy at investigators’ discretion. Chemotherapy options include fludarabine plus cyclophosphamide (FC) for fit patients, chlorambucil (clb) for unfit patients, and bendamustine (B). Median observation time is 12.7 months to date. Findings are summarized below, and fit the known safety profile of OBIN.