Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, Previously untreated chronic lymphocytic leukemia

Abstract

Obinutuzumabis aglycoengineered, type 2 anti-CD20humanizedantibodywith single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900mgday 2, 1000mgday 8 and day 15 of cycle 1; 1000mgday 1 of cycles 2-8) or 2000mg (100mg IV day 1, 900 mg day 2, 1000mg day 3, 2000mg day 8 and day 15 of cycle 1; 2000mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similardemographics: median age 67 years,41%high-risk Rai disease, and10%del(17p)(13.1).ORR(67% vs 49%,P5.08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationshipmay exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up.