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FDA Approves Chemotherapy-Free Regimen, Venetoclax Plus Obinutuzumab, as First-Line Treatment for CLL/SLL


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On May 15, the U.S. Food and Drug Administration (FDA) approved venetoclax (Venclexta) in combination with obinutuzumab (Gazyva) for the treatment of adult patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Approval was based on the CLL14 trial (ClinicalTrials.gov identifier NCT02242942), a randomized (1:1), multicenter, open--label, actively controlled trial of venetoclax in combination with obinutuzumab vs obinutuzumab in combination with chlorambucil in 432 patients with previously untreated CLL with coexisting medical conditions.

Key Outcomes in CLL14

The major efficacy outcome was progression-free survival, as assessed by an independent review committee. The trial demonstrated a statistically significant improvement in progression-free survival for patients who received venetoclax plus obinutuzumab compared with those who received obinutuzumab plus chlorambucil (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.22–0.51; P < .0001). Median progression-free survival was not reached in either arm after a median follow-up duration of 28 months.

The overall response rate was 85% in the venetoclax/obinutuzumab arm compared to 71% in the obinutuzumab/chlorambucil arm (P = .0007. The trial also demonstrated statistically significant improvements in the rates of minimal residual disease negativity (less than one CLL cell per 104 leukocytes) in the bone marrow and peripheral blood. Overall survival data were not mature at this analysis.

In CLL/SLL, the most common adverse reactions (occurring in ≥ 20% of patients) for venetoclax when administered with obinutuzumab, rituximab, or as monotherapy were neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema.

The FDA used the Real-Time Oncology Review and Assessment Aid Pilot Program for this application and granted priority review as well as Orphan Drug and Breakthrough Therapy designations. Approval was granted 3.7 months ahead of the Prescription Drug User Free Act date. 


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