A Phase 1b Study Evaluating the Safety and Efficacy of Venetoclax As Monotherapy or in Combination with Azacitidine for the Treatment of Relapsed/Refractory Myelodysplastic Syndrome

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.565-565
• Main Authors: Zeidan, Amer M., Pollyea, Daniel A, Garcia, Jacqueline S, Brunner, Andrew, Roncolato, Fernando, Borate, Uma, Odenike, Olatoyosi, Bajel, Ashish R., Watson, Anne Marie, Götze, Katharina, Nolte, Florian, Tan, Peter T., Hong, Wan-Jen, Dunbar, Martin, Zhou, Ying, Gressick, Lori, Ainsworth, William, Harb, Jason, Salem, Ahmed Hamed, Hayslip, John, Swords, Ronan, Garcia-Manero, Guillermo
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-124994

▪ Introduction Over-expression of the anti-apoptotic protein BCL-2 in MDS has been implicated in progression and drug resistance in MDS. Venetoclax (Ven), a selective, potent, orally bioavailable BCL-2 inhibitor, was recently approved in combination with HMAs or low dose cytarabine for the frontline management of older unfit pts with AML. In this study, we sought to evaluate the safety and efficacy of Ven in pts with R/R MDS. Methods This is an ongoing phase 1b, open-label, multicenter study in R/R MDS (NCT02966782). Key eligibility criteria include age ≥18 years, failure of HMA after receiving at least 4 cycles of Aza or 4 cycles of decitabine within the previous 5 years, marrow blasts 3 therapies prior to enrollment in the study. Baseline bone marrow blasts were: ≤5% was observed in 16 (35%) pts, >5% and ≤10% in 23 (50%), and >10% in 7 (15%) pts respectively. Cytogenetics risk was evaluated in 27/46 pts and were as follows: Good 12 (44%), Intermediate 9 (33%), and Poor 6 (22%). Overall, 9 pts discontinued study therapy (8 deaths, 1 withdrew consent). The most frequent treatment-emergent adverse events (TEAEs) included neutropenia, thrombocytopenia, nausea, and diarrhea (Table ). Infectious TEAEs included febrile neutropenia and pneumonia. Predominant Grade 3 and 4 TEAEs were hematological and includ