Conference Correspondent

Phase 2 Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed/Refractory CLL

Conference Correspondent - ASH 2018 - CLL
The goal of the triple-agent regimen of obinutuzumab (OBIN), ibrutinib (IBR), and venetoclax (VEN) is to achieve deep remissions and facilitate treatment discontinuation. The previously reported phase 1b cohort on this study established VEN 400 mg daily as the recommended dose for use with the label doses of OBIN and IBR in this combination. To determine response rates, eradication of minimal residual disease (MRD), and progression-free survival (PFS) in relapsed/refractory (R/R) and treatment-naïve chronic lymphocytic leukemia (CLL) with this regimen, 2 separate cohorts were accrued to a phase 2 trial. Here, researchers report their mid-therapy assessment findings.

Patients with previously untreated or R/R CLL requiring therapy were eligible for the study. Treatment was given for 14 cycles of 28 days with OBIN, IBR, and VEN started sequentially over the first 3 cycles.

The study enrolled a total of 50 patients; 25 were previously untreated and 25 were R/R. In terms of safety, hematologic toxicities were most frequent, with 80% of patients experiencing all-grade thrombocytopenia and 76% experiencing neutropenia. The most frequent all-grade nonhematologic toxicities were hypertension (70%), infusion-related reactions (66%), bruising (52%), myalgia (50%), and nausea (50%). Grade ≥3 adverse events included neutropenia (56%) and thrombocytopenia (34%).

The median follow-up for the study was 21.5 months for the R/R cohort and 24.2 months for the previously untreated cohort. The overall response rate (ORR) in R/R patients at end of treatment was 84% for treatment naïve patients and 88% for R/R patients. A total of 67% and 50% of treatment-naïve and R/R patients achieved MRD-negative status at end of therapy, respectively, 28% of whom achieved complete responses in both groups.

In conclusion, the combination of OBIN, IBR, and VEN showed a tolerable safety profile in both R/R and previously untreated CLL patients. This triple-agent regimen has a high ORR in treatment-naïve and R/R patients, with promising early MRD-negative responses. Long-term follow-up is needed to determine PFS.

Rogers KA, et al. ASH 2018. Abstract 693.

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Last modified: December 4, 2018
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