Venetoclax has single-agent antitumor activity in a range of non-Hodgkin lymphoma (NHL) subtypes.

  • Major finding: Venetoclax has single-agent antitumor activity in a range of non-Hodgkin lymphoma (NHL) subtypes.

  • Concept: A phase I dose-escalation study found that venetoclax is well tolerated in patients with NHL.

  • Impact: Venetoclax warrants further investigation alone and in combination therapies to treat patients with NHL.

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The antiapoptotic protein BCL2 is frequently overexpressed in non-Hodgkin lymphoma (NHL), resulting in dysregulated apoptosis. The selective, orally bioavailable BCL2 inhibitor venetoclax has been approved for the treatment of patients with chronic lymphocytic leukemia (CLL) and has demonstrated preclinical activity against multiple subtypes of NHL. Davids and colleagues evaluated the safety and efficacy of venetoclax in a phase I dose-escalation study of 106 patients with NHL, including 28 with mantle cell lymphoma (MCL), 29 with follicular lymphoma (FL), and 34 with diffuse large B-cell lymphoma (DLBCL). Venetoclax was well tolerated; the majority of treatment-related adverse events were grade 1 to 2. Grade 3 to 4 adverse events occurred in 56% of patients. The maximum-tolerated dose was not reached. Responses were observed in 47 of 106 patients (44%), including 14 complete and 33 partial responses. Although the best response rate was achieved in MCL (75%, including complete responses in 21%), antitumor activity was seen across NHL subtypes. The response rate was 38% in patients with FL and 18% in patients with DLBCL. The estimated median progression-free survival was 6 months; 14 months for MCL, 11 months for FL, and 1 month for DLBCL. The estimated 12-month overall survival was 70%. The expression levels of BCL2 did not correspond to the observed responses. Taken together, the results of this phase I study indicate that BCL2 inhibition with venetoclax is well tolerated and has single-agent antitumor activity across NHL subtypes, and the favorable toxicity profile suggests that combining venetoclax with other therapies may be beneficial and warrants further investigation in patients with NHL.

Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-hodgkin lymphoma. J Clin Oncol 2017 Jan 17 [Epub ahead of print].

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