The combination of ibrutinib plus obinutuzumab appeared safe and effective for the first-line treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) providing a chemotherapy-free alternative for treatment-naïve patients.

“Treatment of chronic lymphocytic leukaemia has dramatically evolved with the introduction of B-cell receptor signalling inhibitors,” Carol Moreno, MD, of the Department of Hematology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona in Spain, and colleagues wrote in The Lancet Oncology. “Ibrutinib, a first-in-class, once-daily oral inhibitor of tyrosine-protein kinase BTK (also known as Bruton tyrosine kinase), has shown substantial single-drug efficacy in chronic lymphocytic leukaemia and provides a chemotherapy-free treatment option for this common leukaemia.”

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Moreno and colleagues conducted a randomized, multicenter phase 3 trial among 229 patients with previously untreated CLL or SLL either 65 years old or younger than 65 with coexisting conditions.

Patients were randomly assigned 1:1 to treatment with ibrutinib plus obinutuzumab (oral ibrutinib [420 mg once daily continuously] combined with intravenous obinutuzumab [100 mg on day 1, 900 mg on day 2, 1000 mg on day 8, and 1000 mg on day 15 of cycle 1 and on day 1 of subsequent 28-day cycles, for a total of six cycles]) or chlorambucil plus obinutuzumab (oral chlorambucil [0·5 mg/kg bodyweight on days 1 and 15 of each 28-day cycle for six cycles] combined with the same obinutuzumab regimen.

Median follow up was 31.3 months. Researchers observed a greater median progression-free survival (PFS) among patients treated with ibrutinib-obinutuzumab combination (median not reached; 95% CI, 33.6-non-estimable) compared with chlorambucil plus obinutuzumab (19 months; 95% CI, 15.1-22.1; HR = 0.23; 95% CI, 0.15–0.37; P < .0001).

Estimated 30-month PFS was 79% (95% CI, 70-85) among the ibrutinib plus obinutuzumab group and 31% (95% CI, 23-40) in the chlorambucil plus obinutuzumab group.

The most common grade 3 or 4 adverse events in both groups were neutropenia and thrombocytopenia. Serious adverse events occurred in 58% patients treated with ibrutinib plus obinutuzumab and 35% patients treated with chlorambucil plus obinutuzumab.

One patient died of sudden death in the ibrutinib plus obinutuzumab and one patient died of neuroendocrine carcinoma of the skin in the chlorambucil plus obinutuzumab.

“The ibrutinib plus obinutuzumab regimen had an acceptable safety profile and was tolerated by most patients for up to 3 years,” Moreno and colleagues wrote. “Furthermore, patients given this regimen had better progression-free survival outcomes than those who had the standard chlorambucil plus obinutuzumab combination regimen recommended in consensus treatment guidelines, regardless of risk factors.”