Decitabine Plus All-Trans Retinoic Acid Evaluated in Excess-Blasts MDS

In a study investigating treatment for adults with myelodysplastic syndrome (MDS) featuring excessive blasts, the clinical performance of decitabine plus all-trans retinoic acid was compared with decitabine monotherapy. Its findings were presented at the 66^th American Society of Hematology Annual Meeting & Exposition in San Diego, California.

Lead author Hongyan Tong, PhD, of Zhejiang University in Hangzhou, China, concluded “[t]his combination may be a new treatment option for MDS [with excess blasts] patients,” and highlighted its superior overall response rate (ORR) and progression-free survival (PFS) results.

The multicenter, open-label, randomized controlled trial had a total cohort of 227 patients, and a modified intention-to-treat population of 223 patients. 113 patients received oral all-trans retinoic acid plus decitabine, and 114 received decitabine monotherapy.

Patients were planned to all have at least four treatment cycles, at 28 days each cycle. All patients received 20 mg/m² intravenous decitabine on the first 5 days of each cycle. Patients in the combination therapy group were also administered oral all-trans retinoic acid at 25 mg/m²/day each day of the 28-day cycle, then, from the fifth cycle onward, only on the first 14 days of a cycle.

Over a median follow-up of 30.1 months, the combination therapy and monotherapy groups had overall survival of 23.0 months and 19.3 months, respectively (P = .137), with a hazard ratio (HR) of 0.77. PFS was 14.9 months in the combination therapy group and 10.5 months in the monotherapy group, respectively (P = .032), with an HR of 0.70. The time to acute myeloid leukemia (AML) transformation was 18.9 months with combination therapy and 15.8 months with monotherapy (P = .221), with an HR of 0.81.

In the combination therapy and monotherapy groups, the ORR was 78% and 51%, respectively (P < .001), with an odds ratio (OR) of 3.40. The complete response (CR) rate in the combination therapy group was 23% and in the monotherapy group was 12% (P = .042), with an OR of 2.05. The CR plus bone marrow CR rate was 72% with combination therapy and 49% with monotherapy (P < .001), with an OR of 2.69. The CR plus partial remission plus hematologic improvement rate was 48% with combination therapy and 34% with monotherapy (P =.027), with an OR of 1.84.

Regarding the incidence of serious treatment-emergent adverse events in the combination therapy and monotherapy groups, the rate of hematological-type events was 86% and 80% (P = .254), and of non-hematological-type events was 35% and 23% (P = .057), respectively.

In an off-label disclosure, the presenting investigators indicated that all-trans retinoic acid is recommended as acute promyelocytic leukemia treatment but is not very effective for AML unless the PML-RARA fusion protein is present.

“However, preclinical studies indicated that [hypomethylating agents] may render AML cells more sensitive to [all-trans retinoic acid]. Reciprocally, [all-trans retinoic acid] could potentiate the cytotoxic effects of decitabine,” the investigators wrote.

Reference

Tong H, Zhou X, Lin Y, et al. Decitabine plus all-trans retinoic acid versus decitabine monotherapy for myelodysplastic syndromes with excess blasts: a multicentre, randomized controlled trial. Abstract #663. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 7-10, 2024; San Diego, California.