Initial Results of a Phase I/II Study of Venetoclax in Combination with Azacitidine in Treatment-Naive and Relapsed/Refractory High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
To date 9 pts were enrolled. Four pts received VEN at 100mg dose, 3 pts at 200mg dose, and 2 pts at 400mg dose on days 1-7. There has been no protocol defined DLTs. The median age was 66 years (range, 59-83), 89% were male, 67% with MDS, 67% with normal karyotype. Five pts (56%) were treatment-naive, and 4 (44%) with R/R disease. Of the treatment-naive cohort (N=5), 4/5 (80%) pts had normal karyotype and none had TP53 mutations. ORR rate in this treatment-naive cohort was 100%, all pts achieving mCR, of which 1 (20%) had neutrophil response. Of the R/R cohort (N=4), cytogenetics were normal in 2/4 (50%) and complex in 2/4 (50%), and 2/4 (50%) had TP53 mutations. ORR in this R/R cohort was 3/4 (75%), all achieving mCR. One pt (25%) had stable disease (Table 1 and Figure 1). With a median follow-up duration of 3.6 months (95% CI: 1.4-8.4), 3 (33%) had disease progression and 1 (11%) died. Pts received median 2 courses of therapy (range, 1-4). One pt went to transplant. Median progression-free survival (PFS) for the entire cohort was 4.6 months (95% CI: 3.4-NA) and median OS has not been reached (Figure 2). Median duration of response is 4.1 months (95% CI: 2.4-NA). Possibly/probably related grade 3/4 adverse events included neutropenia in 4/9 (44%), thrombocytopenia in 3/9 (33%), and anemia in 1/9 (11%) pts. There were no grade 5 events (Table 2).