Venetoclax plus azacitidine demonstrating efficacy for high-risk myelodysplastic syndromes

1. In patients with treatment-naive high-risk myelodysplastic syndromes (HR MDS), the use of venetoclax (14 days) plus azacitidine was well tolerated.

2. In patients with treatment-naive HR MDS, venetoclax plus azacitidine resulted in a 26-month median overall survival (mOS) rate with a complete response (CR) observed in 29.9% of patients.

Evidence Rating Level: 2 (Good)

HR MDS represents a heterogeneous group of hematological disorders with increased likelihood of progressing to acute myeloid leukemia (AML). Azacitidine is currently the first line treatment for HR MDS, but further research is required to delay time to progression and to improve survival. This open-label, multicentre phase 1b study therefore sought to investigate the safety of combining venetoclax and azacitidine in patients with HR MDS. Patients over the age of 18 with no prior treatment for MDS were included in the study and successively enrolled into one of three dose escalation cohorts receiving increasing dosages of venetoclax for 14 days in combination with azacitidine. 107 patients (median age[range], 68 years[26-87]; 69.2% male) received at least 1 dose of venetoclax at the recommended phase 2 dose (RP2D) of 400 mg of venetoclax and were included in safey and efficacy analysis. 10 patients (9.3%) required treatment discontinuation because of an adverse event (AE). CR was observed in 29.9% (n = 32; 95% CI, 21.4-39.5) of patients receiving RP2D and the mOS was 26.0 months. All patients treated at RP2D experienced at least 1 treatment-emergent adverse event (TEAE) and 56 (52.3%) patients require venetoclax dose reduction for any reason. Overall, this study found the use of venetoclax plus azacitidine in patients with treatment-naive HR MDS was well tolerated and was associated with an mOS of 26.0 months.

Click to read the study in Blood

Image: PD

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