Reduced-Intensity Conditioning Transplant Superior to Continuous 5-Azacitidine in Older Patients With MDS

In older patients with advanced myelodysplastic syndromes (MDS), reduced-intensity conditioning allogeneic hematopoietic cell transplantation (HCT) improved event-free survival (EFS) compared with continuous 5-azacitidine therapy. This was according to findings from the VidazaAllo study published in the Journal of Clinical Oncology.

While previous research suggested HCT may be too toxic for older patients with MDS, the VidazaAllo investigators questioned whether transplant could be a potentially curative option for this patient population. Findings from the new study also call into question the role of 5-azacitidine as pretreatment to transplant, given that many participants treated with the therapy progressed or died from toxicity.

The open-label, phase II study enrolled patients with MDS who had initially received 5-azacitidine 75 mg/m2 once a day for four treatment cycles. At baseline, patients’ median age was 63 years (range = 55-70) and the majority of participants were male. Most patients had an Eastern Cooperative Oncology Group score of 1 (n=73) and International Prognostic Scoring System (IPSS) intermediate-2 (n=84) or high-risk (n=70) disease.

After four cycles of 5-azacitidine, patients who experienced a response or stable disease were assigned to receive either continuous 5-azacitidine until disease progression or unacceptable toxicity (arm A; n=27) or HCT after a reduced-intensity conditioning regimen (arm B; n=81). In cases where no human leukocyte antigen (HLA)-compatible donor was found, patients were assigned to continuous 5-azacitidine. If an HLA-compatible donor was found, patients were assigned to arm B.

Initially, a total of 162 patients were enrolled in the induction phase, but the sample size dropped to 108 at the start of the subsequent treatment allocation. “The high dropout rate of patients during the induction phase with 5-azacitidine suggests, however, that timing of HCT is essential and probably should be done as soon as a compatible donor is available,” the researchers wrote. They added that “an earlier HCT may also result in a higher nonrelapse mortality [rate] because the 5-azacitidine pretreatment can be regarded as patient selection.”

Of the 162 patients who initiated 5-azacitidine induction chemotherapy, approximately 7% died during 5-azacitidine pretreatment, and 16% had disease that progressed. Following assignment to either continuous 5-azacitidine or HCT, there was no incidence of treatment-related mortality (TRM) in the 5-azacitidine arm. In contrast, the cumulative one-year incidence of TRM following HCT was 19% (95% CI 11-28; p=0.0065).

A total of 26 patients experienced either relapse or progression during the 5-azacitidine induction phase. Following allocation, however, all 27 patients in the continuous 5-azacitidine group had disease relapse or progression, while only 13.6% of patients in the HCT arm experienced relapse or progression during the follow-up period.

As shown in the TABLE, patients in the HCT group also had a significantly higher three-year EFS compared with patients in the continuous 5-azacitidine arm (34% vs. 0%, respectively; p<0.0001).

The authors also reported that more than half of patients (n=14) allocated to continuous 5-azacitidine experienced disease progression and underwent salvage HCT with an alternative HLA-mismatched donor.

There was no difference between arms in terms of three-year overall survival (OS; 50% vs. 32%; p=0.12), and, while the estimated OS was higher in the HCT arm (49% vs. 29%), this difference was not statistically significant (p=0.3). Survival was highest in patients older than 65, with IPSS intermediate-2 disease, and in remission at transplant.

Limitations of this study included its relatively small sample size and the focus on mostly older patients, which may limit generalizability of the findings in younger patients with lower-risk MDS.

Study authors report relationships with Bristol Myers Squibb, the manufacturer of 5-azacitidine.


Kröger N, Sockel K, Wolschke C, et al. Comparison between 5-azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo Study) [published online ahead of print, 2021 Jul 20]. J Clin Oncol. 2021;JCO2002724. doi: 10.1200/JCO.20.02724.