Results from the CLL11 Study: Salvage Therapy with Obinutuzumab plus Chlorambucil in Patients with CLL and Comorbidities
Chemoimmunotherapy with the anti-CD20 monoclonal antibody obinutuzumab plus chlorambucil—the G-Clb regimen—demonstrated clinical benefit in patients with previously untreated CLL and comorbidities (Goede V, et al. Leukemia. 2013;27:1172-1174). Goede and colleagues examined the safety and efficacy of G-Clb as salvage therapy in a subpopulation of patients who had been treated with chlorambucil alone in the CLL11 study (Blood. 2014;124. Abstract 3327). This study included 30 patients who had received chlorambucil alone as frontline treatment, but who developed progressive CLL ?6 months after the end of chlorambucil therapy and were offered the G-Clb regimen as salvage therapy. These patients exhibited a high comorbidity burden, with a median Clinical Illness Rating Scale score (CIRS) of 8 and reduced renal function; del11q and del17p were present in 12% and 20% of the patients, respectively, and 64% of the patients had unmutated IGVH genes.
After 6 cycles of therapy with G-Clb and a median observation of 23 months, 87% of the patients responded to the treatment, including 7% CR, 3% CR incomplete, and 77% partial response. Of the 13% nonresponders, 7% had stable disease and only 1 patient had progressive disease. Minimal residual disease negativity in bone marrow and/or in peripheral blood after receiving G-Clb was achieved in 23% of patients. The median PFS from the start of treatment with G-Clb was 17.2 months, and the PFS in these patients was 17.2 months. Grade 3/4 treatment-related AEs occurred in 67% of the patients, including neutropenia (33%), anemia (7%), thrombocytopenia (10%), and infection (13%).
The researchers concluded that G-Clb is a rational choice as salvage therapy for patients with CLL who are refractory to previous chemotherapy with chlorambucil. Indeed, they suggested that these data provide a rationale for treating CLL with G-Clb in the frontline setting rather than later in the treatment sequence.