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Azacitidine Improves RBC-TI Rates in Patients with Lower-Risk MDS
CC-486—the oral formulation of azacitidine—significantly improved RBC transfusion independence (RBC-TI) rates and induced durable bilineage improvements in patients with lower-risk myelodysplastic syndromes (LR-MDS) and high-risk disease features, according to a phase 3 clinical trial published in the Journal of Clinical Oncology (2021 March 25. Epub ahead of print).
Guillermo Garcia-Manero, MD, Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, and colleagues, conducted this study to discover more treatment options for patients with LR-MDS by evaluating CC-486 in patients with International Prognostic Scoring System LR-MDS and RBC transfusion-dependent anemia and thrombocytopenia.
A cohort of 216 patients (age ≥ 18 years) with IPSS-defined LD-MDS were randomly assigned to receive either 300 mg of CC-486 (n=107) or placebo (n=109) once daily for 21 days per 28-day cycle. The primary end point was RBC-TI lasting ≥ 56 consecutive days.
Significantly more patients in the CC-486 arm than the placebo arm achieved RBC-TI, with median durations of 11.1 and 5 months (30.8% v 11.1%, respectively; odds ratio [OR], 3.6 [95% CI, 1.7-7.4]; p=.0002). The median time to RBCI-TI was 2.4 months in the CC-486 arm and 2 months in the placebo arm.
A hematologic improvement in the erythroid (HI-E) response was seen in 46 patients (43%) in the CC-486 arm and 34 patients (31.5%) in the placebo arm. Reductions of ≥ 4 RBC units were attained by 42.1% and 30.6% of patients, respectively, with median durations of 10 and 2.3 months. More CC-486 patients had ≥ 1.5 g/dL hemoglobin increases from baseline (23.4%, 4.6%). Platelet hematologic improvement rate was higher with CC-486 (24.3%, 6.5%). There was no significant difference in the estimated median overall survival (OS) between CC-486 and placebo (17.3 v 16.2 months, p=.96).
The most frequently reported adverse events in both arms included hematologic and low-grade GI events. In the CC-486 arm, 90% of patients experienced a grade 3-4 adverse event, and in the placebo arm, 73% had one.
The overall death rate was also similar between the arms, but there was an imbalance seen early during the first 56 days, (CC-486, n=16; placebo, n=6), mostly related to infections.
“Further evaluation of CC-486 in MDS in needed, including rational identification of patients most likely to benefit from the drug,” concluded Garcia-Manero and colleagues.—Emily Bader
