INTRODUCTION: Venetoclax is a highly effective agent in chronic lymphocytic leukemia and acute myeloid leukemia. Phase I/II clinical trials have shown it to be safe and effective in non-Hodgkin lymphoma (NHL). Adverse events were consistent with package labeling despite escalation to high doses. To the best of our knowledge, venetoclax use outside the setting of a clinical trial of NHL has not been reported. PATIENTS AND METHODS: We conducted a single-center, retrospective study of 34 adult patients who had been treated off-label with venetoclax-containing regimens from 2016 to 2018. RESULTS: Of the 34 patients with NHL treated with venetoclax therapy, 13 had had high-grade B-cell lymphoma/diffuse large B-cell lymphoma, 10 mantle cell lymphoma, 5 transformed follicular lymphoma, 2 Richter transformation, 2 marginal zone lymphoma, 1 follicular lymphoma, and 1 post-transplant lymphoproliferative disorder. The patients had received a median of 4 previous therapies. The overall response rate was 26% (3% with a complete response and 35% with stable disease). The median venetoclax dose achieved was 400 mg. Of those receiving combination therapy, 18% had undergone radiation and 62% had received other systemic antineoplastic therapy. The median progression-free and overall survival for the cohort was 2 and 4.5 months, respectively. Adverse events occurred in 76% of the patients during venetoclax therapy. The adverse events included neutropenia, thrombocytopenia, tumor lysis syndrome, infection, neutropenic fever, diarrhea, and 1 opportunistic infection. CONCLUSION: Venetoclax therapy in a real-world cohort offered modest benefits in heavily pretreated patients. Adverse events were observed at a greater incidence than in the clinical trials. A wide heterogeneity of venetoclax dose escalation, multiagent combinations, and timing of initiation were identified and require investigation in subsequent clinical trials.
INTRODUCTION: Venetoclax is a highly effective agent in chronic lymphocytic leukemia and acute myeloid leukemia. Phase I/II clinical trials have shown it to be safe and effective in non-Hodgkin lymphoma (NHL). Adverse events were consistent with package labeling despite escalation to high doses. To the best of our knowledge, venetoclax use outside the setting of a clinical trial of NHL has not been reported. PATIENTS AND METHODS: We conducted a single-center, retrospective study of 34 adult patients who had been treated off-label with venetoclax-containing regimens from 2016 to 2018. RESULTS: Of the 34 patients with NHL treated with venetoclax therapy, 13 had had high-grade B-cell lymphoma/diffuse large B-cell lymphoma, 10 mantle cell lymphoma, 5 transformed follicular lymphoma, 2 Richter transformation, 2 marginal zone lymphoma, 1 follicular lymphoma, and 1 post-transplant lymphoproliferative disorder. The patients had received a median of 4 previous therapies. The overall response rate was 26% (3% with a complete response and 35% with stable disease). The median venetoclax dose achieved was 400 mg. Of those receiving combination therapy, 18% had undergone radiation and 62% had received other systemic antineoplastic therapy. The median progression-free and overall survival for the cohort was 2 and 4.5 months, respectively. Adverse events occurred in 76% of the patients during venetoclax therapy. The adverse events included neutropenia, thrombocytopenia, tumor lysis syndrome, infection, neutropenic fever, diarrhea, and 1 opportunistic infection. CONCLUSION: Venetoclax therapy in a real-world cohort offered modest benefits in heavily pretreated patients. Adverse events were observed at a greater incidence than in the clinical trials. A wide heterogeneity of venetoclax dose escalation, multiagent combinations, and timing of initiation were identified and require investigation in subsequent clinical trials.