In the German phase II VidazaAllo study reported in the Journal of Clinical Oncology, Kröger et al found that switching from azacitidine to reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT) contingent upon donor availability was associated with better outcomes vs continuous azacitidine in older patients with advanced myelodysplastic syndrome (MDS).
Study Details
The multicenter trial enrolled patients aged 55 to 70 years (median = 63 years; range = 55–72 years) between June 2011 and November 2016. Patients received four to six cycles of azacitidine followed by human leukocyte antigen (HLA)-compatible (10 of 10 alleles) HSCT after reduced-intensity conditioning or by continuous azacitidine until disease progression or unacceptable toxicity if no donor was identified. Reduced-intensity conditioning consisted of a busulfan/fludarabine regimen or a regimen of sequential amsacrine, cytosine arabinoside, and fludarabine followed by busulfan/fludarabine (FLAMSA). The primary endpoint was 3-year overall survival; 3-year event-free survival was a secondary endpoint.
Key Findings
Among a total of 190 enrolled patients, 28 did not fulfill inclusion criteria (n = 20), died (n = 2), withdrew informed consent (n = 5), or were excluded for an unknown reason (n = 1).
In older patients with MDS, reduced-intensity conditioning HSCT resulted in a significantly improved event-free survival in comparison with continuous 5-azacytidine therapy. Bridging with 5-azacytidine to HSCT before is associated with a considerable rate of dropouts because of progression, mortality, and adverse events.— Kröger et al
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Induction with azacitidine was started in 162 patients; however, only 108 (67%) were eligible for subsequent allocation to HSCT (n = 81) or continuation of azacitidine (n = 27). Reasons for discontinuation of treatment during induction consisted of disease progression (n = 26), death (n = 12, mainly due to infectious complications), adverse events (n = 7), withdrawal of consent (n = 2), or other reasons (n = 7); overall, 7% of patients died during azacitidine treatment before treatment allocation to HSCT or continued azacitidine treatment.
After allocation to HSCT or continuous azacitidine, no treatment-related mortality was observed in those receiving azacitidine, whereas cumulative treatment-related mortality at 1 year after HSCT was 19%.
At 3 years, overall survival was 50% (95% confidence interval [CI] = 39%–61%) after HSCT vs 32% (95% CI = 14%–52%) with continuous azacitidine (P = .12). Event-free survival was 34% (95% CI = 22%–47%) vs 0% (P < .0001). A total of 14 patients whose disease progressed during continuous azacitidine treatment received a salvage allograft from an alternative donor; of these patients, 43% were alive at last follow-up.
The investigators concluded: “In older patients with MDS, reduced-intensity conditioning HSCT resulted in a significantly improved event-free survival in comparison with continuous azacitidine therapy. Bridging with azacitidine to HSCT before is associated with a considerable rate of dropouts because of progression, mortality, and adverse events.”
Nicolaus Kröger, MD, of the Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by a research grant from Celgene. For full disclosures of the study authors, visit ascopubs.org.
