Activity of Decitabine (DEC) Combined with All-Trans Retinoic Acid (ATRA) in oligoblastic AML: Results from a Randomized 2x2 Phase II Trial (DECIDER)

Abstract DNA-hypomethylating agents are the backbone for non-intensive combination treatments of AML/MDS. In elderly AML patients, a combination of DEC+ATRA resulted in an improved response rate and survival compared to DEC without ATRA, also in those with prior hematologic disorder; additional valproic acid did not play a significant role (Lübbert et al., JCO 2020). To evaluate whether patients with oligoblastic AML also benefit from this combination, patients from the DECIDER cohort with 20-30% bone marrow blasts were analyzed for clinical outcome in this exploratory, not pre-planned subgroup analysis. They were newly diagnosed with AML, were unfit for induction and received DEC 20 mg/m2 day 1-5 in all arms, ATRA day 6-28 (arms C/D) and VPA p.o. continuously from day 6 (arms B/D) of each 28-day course. 200 patients were randomized and treated, 56 with oligoblastic AML. Of these, six attained a CR, 7 a CRi, and 1 a PR, resulting in an ORR of 25%. The effect on ORR of ATRA vs no ATRA was 31.8 vs 20.6% with an odds ratio of 1.85 (95% CI 0.54-6.37, p=0.33). With 48 deaths out of 56 patients, median OS was 9.1 months. The effect on OS of ATRA vs. no ATRA was 11.5 vs 7.6 months with a HR of 0.71 (95% CI 0.40-1.29, p=0.26). In elderly patients with oligoblastic AML ineligible for induction chemotherapy, the addition of ATRA to DEC resulted in a clinically meaningful survival benefit. We hypothesize that the combination of an HMA with a retinoid may also be active in MDS with excess blasts.