Recombinant human erythropoietin plus all-trans retinoic acid and testosterone undecanoate for the treatment of anemia in patients with lower-risk myelodysplastic syndromes: a multicenter, single-arm, prospective trial

Erythropoiesis-stimulating agents (ESA) achieve hematological improvement-erythroid (HI-E) in only 30% of ESA-naïve lower- risk myelodysplastic syndrome (LR-MDS) patients with anemia, highlighting the need for developing novel drugs or new treatment strategies to improve the outcome of these patients. We conducted this multicenter, single-arm trial to investigate the efficacy and safety of a triple regimen consisting of recombinant human erythropoietin (rhEPO), all-trans retinoic acid (ATRA) and testosterone undecanoate in patients with anemia due to lower-risk MDS based on Revised International Prognostic Scoring System. Eligible patients received rhEPO 10,000 IU/day, oral ATRA 25 mg/m2/day and oral testosterone undecanoate 80 mg twice daily for 12 weeks. The primary endpoint was the proportion of patients achieving HI-E during 12 weeks of treatment. Of 52 eligible patients, 32 (61.5%, 95% confidence interval [CI]: 48.0-73.5%) achieved HI-E, meeting the primary endpoint. Fifteen patients (65.2% [15/23]) with baseline serum erythropoietin (EPO) ≤500 IU/L had HI-E versus 58.6% of those (17/29) with baseline serum EPO >500 IU/L. More patients with very low or low risk had HI-E than those with intermediate risk (73.3% vs. 45.5%; P=0.041) and fewer patients with mutated ASXL1 had HI-E than those with wild-type ASXL1 (33.3% vs. 70.0%; P=0.040). The regimen had an acceptable safety profile compatible with individual agents. In conclusion, the triple regimen of rhEPO combined with ATRA and testosterone undecanoate attained HI-E in approximately 61.5% of patients regardless of baseline serum EPO levels, supporting further development of this regimen for LR-MDS patients with anemia. This study was registered at http://www.chictr.org.cn (Identifier: ChiCTR2000032845).