Outcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure

Abstract

Purpose Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. Patients and Methods Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). Results The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. Conclusion Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population.

Survival benefits with transplantation in secondary AML evolving from myelodysplastic syndrome with hypomethylating treatment failure

“…The observation that higher BM blast count was a poor predictor for survival and that there was a poor response rate to intensive chemotherapy (CTx) for sAML with a prior history of HMA prompted us to investigate the role of active treatment in patients with sAML evolving from MDS-HTF (sAML/ MDS-HTF). 8,9 None of the prior studies have analyzed the impact of SCT on the survival of patients with sAML/MDS-HTF, although one group reported a poor outcome in patients with HTF in whom AZA was administered for sAML. 10 The aim of the present study was to evaluate the influences of therapeutic modalities on the survival of patients with sAML/MDS-HTF by analyzing clinical outcomes according to the treatment option.…”

“…4 Recent reports have shown a poor prognosis for patients with MDS experiencing HTF (MDS-HTF). Jabbour et al 8 reported that patients with HTF following DAC treatment had a median survival of 4.3 months. Prebet et al 8 showed a median survival of 5.6 months and a 2-year survival probability of 15.0% in patients with HTF following AZA treatment.…”

“…Jabbour et al 8 reported that patients with HTF following DAC treatment had a median survival of 4.3 months. Prebet et al 8 showed a median survival of 5.6 months and a 2-year survival probability of 15.0% in patients with HTF following AZA treatment. The authors showed that allo-SCT or investigational therapy resulted in better survival compared with conventional care in patients with MDS-HTF.…”

Lack of cross‐resistance to FF‐10501, an inhibitor of inosine‐5′‐monophosphate dehydrogenase, in azacitidine‐resistant cell lines selected from SKM‐1 and MOLM‐13 leukemia cell lines

“…Prognosis after azacitidine failure is poor both in MDS patients (Prébet et al. 2011), and in AML patients progressed from MDS (Prébet et al. 2012).…”

Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia

“…Small case series have shown that decitabine treatment after azacitidine failure yields modest responses (ORR: 0%-28%) that are generally short lived [48,[50][51][52][53]; however, this is not currently standard treatment practice. The current standard of care for patients with MDS who have not responded after at least six cycles of azacitidine treatment is to consider clinical trials [48,49] or proceed with SCT [51].…”