In a phase 1 study, patients with relapsed/refractory multiple myeloma (MM) received venetoclax monotherapy at escalating doses of 300 to 1200 mg, after a two-week lead-in period. Dexamethasone was added upon disease progression. The study enrolled 66 patients, with 30 in dose-escalation cohorts and 36 in the safety expansion group. These patients had undergone a median of five prior therapies, with 61% being double refractory to bortezomib and lenalidomide. Notably, 46% had the t(11;14) genetic abnormality. 

The overall response rate (ORR) to venetoclax was 21%, with 15% of patients achieving very good partial response or better. Most responses (86%) were observed in the subset of patients with the t(11;14) abnormality, where the ORR was 40%, and 27% achieved a very good partial response or better. Biomarker analysis revealed that the response to venetoclax was higher in patients with elevated BCL2:BCL2L1 and BCL2:MCL1 mRNA expression ratios. The study concludes that venetoclax monotherapy, administered at a daily dose of up to 1200 mg, is safe and demonstrates significant activity against MM, particularly in patients with the t(11;14) translocation and a favorable BCL-2 family gene expression profile.

Reference: Kumar S, Kaufman JL, Gasparetto C, et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood. 2017 Nov 30;130(22):2401-2409. doi: 10.1182/blood-2017-06-788786. Epub 2017 Oct 10. PMID: 29018077.