Venetoclax was well-tolerated with variable efficacy against various non-Hodgkin lymphoma (NHL) subtypes, according results from cohort B of the M12-175 trial (ClinicalTrials.gov 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.
Reference
- 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]
