Venetoclax Studied in Relapsed or Refractory Non-Hodgkin Lymphoma


Key Points

  • The highest response rates to venetoclax were seen in patients with mantle cell lymphoma.
  • The most common grade 3 or 4 toxicities associated with venetoclax were hematologic events.

The BCL-2 inhibitor venetoclax (Venclexta) was found to be active in patients with relapsed or refractory non-Hodgkin lymphoma (NHL), according to a phase I study reported by Davids et al in the Journal of Clinical Oncology. Further study of this agent, including in combination therapy to augment response rates and durability, is ongoing.

Study Details

In the study, 106 patients with relapsed or refractory NHL received venetoclax once daily until disease progression or unacceptable toxicity at doses of 200 to 1,200 mg in dose-escalation and safety-expansion cohorts. Patients included those with mantle cell lymphoma (n = 28), follicular lymphoma (n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenström macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Doses received were ≤ 400 mg in 22 patients, 600 to 900 mg in 33 patients, and 1,200 mg in 51 patients.

Adverse Events

The most common adverse events of any grade were nausea (48%), diarrhea (45%), and fatigue (42%). Grade 3 to 4 adverse events occurred in 56%, with the most common being anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Serious adverse events occurred in 25%. Laboratory tumor-lysis syndrome was observed in three patients, with no cases of clinical tumor-lysis syndrome being observed.

Response Rates

The overall response rate was 44%, including response rates of 75% in mantle cell lymphoma, 38% in follicular lymphoma, and 18% in DLBCL. Overall, median progression-free survival was 6 months, including 14 months in mantle cell lymphoma, 11 months in follicular lymphoma, and 1 month in DLBCL.

The investigators concluded: “Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in [follicular lymphoma] and DLBCL, with 800 mg being sufficient to consistently achieve durable response in [mantle cell lymphoma]. Additional investigations including combination therapy to augment response rates and durability are ongoing.”

The study was supported by AbbVie and Genentech.

Matthew S. Davids, MD, MMSc, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.