Comparing 5-Azacitidine Versus Transplant in Older Patients With MDS

In a prospective multicenter study, older patients with myelodysplastic syndromes (MDS) who underwent reduced-intensity allogeneic hematopoietic stem cell transplantation (alloHSCT) had longer event-free survival (EFS) compared with those who received continuous 5-azacitidine therapy. Results from the study were published in the Journal of Clinical Oncology.

“In contrast to 5-azacitidine, [alloHSCT] represents a curative treatment strategy for patients with [MDS], but therapy-related mortality (TRM) limits its broader use in elderly patients with MDS,” the authors, led by Nicolaus Kröger, MD, from University Medical Center Hamburg-Eppendorf in Germany, wrote. “The present prospective multicenter study compared HSCT following 5-azacitidine pretreatment with continuous 5-azacitidine treatment in patients with higher-risk MDS age 55 to 70 years.”

The study enrolled 190 patients (median age, 63 years). Patients received 4 to 6 cycles of 5-azacitidine followed by either HLA-compatible alloHSCT after reduced-intensity conditioning or continuous 5-azacitidine if no donor was identified.

A total of 162 patients received 5-azacitidine induction, but only 108 (67%) were eligible for subsequent allocation to HSCT (n = 81) or continuation of 5-aza (n = 27). Reasons for this type of discontinuation included disease progression (n = 26), death (n = 12), or other reasons (n = 16). Seven percent of the patients who started 5-azacitidine induction died before treatment allocation.

The cumulative incidence of TRM after alloHSCT at one year was 19%. For patients who received alloHSCT following 5-azacitidine induction, rates of three-year EFS and three-year overall survival were 34% and 50%, compared with 0% and 32% in the continuous 5-azacitidine group, respectively. Fourteen patients progressing after continuous 5-azacitidine received a salvage allograft from an alternative donor, and 43% were alive at last follow-up.

These findings suggest that older patients with MDS have significantly improved survival with alloHSCT compared with continuous 5-azacitidine. The authors also noted that “bridging with 5-azacitidine to HSCT before is associated with a considerable rate of dropouts because of progression, mortality, and adverse events.”