Long-Term Outcome Of Higher-Risk MDS Patients Treated With Azacitidine: Single Centre Experience

The primary goals of treatment for patients with higher-risk MDS are to improve bone marrow function, suppress AML transformation and prolong survival. The international phase 3 trial, AZA-001, established that azacitidine (AZA) significantly prolonged median overall survival and significantly delayed median time to AML transformation as compared with conventional care regimens. AZA was also associated with significant improvements in other clinically relevant outcomes, including reducing the need for transfusion, hospitalization and intravenous antimicrobials, and improving quality of life. Although several clinical trials have examined the safety of AZA, limited data are available about the long-term use of this drug.

We report a retrospective analysis of the outcome of 16 higher-risk MDS patients (M/F: 7/9) treated at our Institution with AZA, from June 2008 to June 2013, with a median follow-up of 33.5 months (range 24-60) after the start of AZA to determine the characteristics of this subset of long-term survivors.

Median age at diagnosis was 68 years (range 51-75) and PS was <2 in 13 cases (81.2%). Diagnosis according to the 2008 WHO Classification was refractory anemia with excess blasts (RAEB)-1 in 7 cases and RAEB-2 in 9 cases. Cytogenetic risk was low in 6 cases (37.5 %; all with normal karyotype) and high in 10 cases (62.5%; all with complex abnormalities). All patients received AZA administered subcutaneously at a dosage of 75 mg/m2 daily for 7 days, repeating the cycle every 28 days; median number of AZA cycles received was 25 (range 19-56).

Results

According to International Working Group 2006 criteria, 4 patients (25%) achieved complete response, 7 patients (44%) achieved partial response, and 5 (31%) stable disease. 13 patients (81%) are still alive and continuing to receive AZA. Two patients (12.5 %) died due to disease progression, one after 27 months and one after 29 months after the start of AZA. One patient died to infection disease (pneumonia). AZA treatment has lasted more than 3 years in 4 (25%) of the 16 patients. Peripheral cytopenias were the most common advent events for treatment.

Allogeneic stem cell transplantation remains the only potentially curative treatment for MDS but the vast majority of patients with MDS are ineligible for transplantation because of comorbidities, advanced age, or lack of a suitable donor. Study in a larger series of patients is warranted, but our experience shows that in the absence of intolerable toxicity or disease progression, continued AZA treatment seems to improve the outcome of higher-risk MDS patients who are not eligible for transplantation.

No relevant conflicts of interest to declare.