Venetoclax was well-tolerated with variable efficacy against various non-Hodgkin lymphoma (NHL) subtypes, according results from cohort B of the M12-175 trial ( Identifier: NCT01328626), a first-in-human study published in the Journal of Clinical Oncology.1

Venetoclax is a highly selective BCL-2 inhibitor; BCL-2 abnormalities are present in follicular lymphoma (FL), diffuse large B-cell lymphomas (DLBCL), and mantle cell lymphoma (MCL). This analysis evaluated the safety, pharmacokinetics, and efficacy of venetoclax in patients with NHL.

Cohort B of the M12-175 trial treated 106 patients with relapsed or refractory NHL with venetoclax once daily until disease progression or unacceptable toxicity (target doses, 200 to 1200 mg).

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The NHL subtypes included MCL, FL, DLBCL, DLBCL arising from CLL Richter transformation (DLBCL-RT), Waldenström macroglobulinemia (WM), and marginal zone lymphoma (MZL).

Treatment-emergent adverse events occurred in 97% of patient, most of which were grade 1 to 2 in severity. Grade 3/4 events occurred in 56% of patients, with the most common including anemia, neutropenia, and thrombocytopenia. More common serious adverse events (3% each) were hyponatremia, influenza, and lower respiratory tract infection. A maximum tolerated dose was not reached.

The overall response rate of venetoclax was 44%; the response rate was 75% in MCL, 38% in FL, 18% in DLBCL, 43% in DLBCL-RT, 67% in MZL, and 100% in WM.

The overall median progression-free survival was 6 months, which varied from 14 months among patients with MCL to 11 months in FL and 1 month in DLBCL.

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The investigators determined that 800 mg and 1200 mg of venetoclax are the recommended single-agent dose for MCL and FL or DLBCL, respectively. The mechanism of action of venetoclax suggests it may partner well in combination regimens.


  1. Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patietns with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.70.4320 [Epub ahead of print]