Azacitidine Treatment Failure Outcomes in Patients with MDS or AML

December 2011, Vol 2, No 7 - In the Literature


Azacitidine is the current standard of care for high-risk myelodysplastic syndrome (MDS), but many patients experience treatment failure. No study has previously analyzed patient outcomes of those who fail azacitidine therapy. This new analysis combined data from 4 international clinical trials to describe patient outcomes after failing azacitidine treatment (Prébet T, et al. J Clin Oncol. 2011;29:3322-3327).

The study combined data of 435 patients with high-risk MDS or with acute myeloid leukemia (AML) who demonstrated treatment failure after receiving azacitidine therapy between 2000 and 2009. Of these patients, 302 had received therapy for MDS, and 133 had received therapy for AML. The median follow-up after failing azacitidine therapy was 15 months.

The median OS in the combined 4 trials was 5.6 months, and the 1-year and 2-year survival probability was 28.9% and 15.3%, respectively. This study shows that there is no standard second-line chemotherapy treatment for patients with high-risk MDS or acute AML after azacitidine failure. Best supportive care or cytotoxic chemotherapy (ie, hydroxyurea, mercaptopurine, low-dose cytarabine, low-dose melphalan, or intense AMLlike chemotherapy) were not of any substantial benefit.

Postfailure treatment data available for 270 patients showed worst prognosis for those who received un – known salvage therapy (OS, 3.6 months) or best supportive care (OS, 4.1 months) and was best for those who received investigational agents— DNA methyltransferase enzyme in – hi bitor alone or in combination with histone deacetylase inhibitor, thalidomide- derivative (ie, lenalidomide or thalidomide), treatments for patients in clinical trials evaluating nonregistered drugs (including immunotherapy, bryostatin, triapine, farnesyl transferase inhibitors, and mammalian target of rapamycin inhibitors)—(OS, 13.2 months) or allogeneic stem-cell transplantation (OS, 19.5 months). Poor outcomes were also observed in patients who received low-dose chemotherapy (OS, 7.3 months) or intensive AML-like chemotherapy (OS, 8.9 months).