Influence of Different Treatment Modalities On the Prognosis of Patients with High Risk MDS Aged Above 60 Years. A Matched-Pairs Analysis.

Patients with high-risk MDS have a poor prognosis, partly attributable to a high rate of leukemic transformation. In this patient group, treatment approaches include hypomethylating agents, i.e. decitabine or 5-azacytidine, low-dose chemotherapy with cytosine arabinoside (LD-AraC), and induction chemotherapy as used in the treatment of acute myeloid leukaemia. Nevertheless, many patients, especially those aged above 60 years, receive best supportive care (BSC) only. In order to evaluate the use of hypomethylating agents, LD-AraC, and induction chemotherapy, we performed a matched-pairs analysis, comparing each of these interventions with matched BSC patients from the Düsseldorf MDS Registry, which now provides follow-up data on more than 3600 patients.

Sixty-seven patients with high-risk MDS aged over 60 were treated with hypomethylating agents, of whom 28 received decitabine, 33 received 5-azacytidine, and 6 received both drugs in succession. LD-AraC was given to 58 patients, and 87 patients underwent induction chemotherapy. A matched partner receiving only BSC was sought in the Düsseldorf MDS Registry for each patient in these treatment groups. Patients were matched according to age, gender, WHO type and IPSS score.

Median age of patients receiving hypomethylating agents was 70 years (60–79). The median survival time in this treatment group was 24 months, not differing significantly between patients treated with decitabine and those receiving 5-azacytidine. The median number of treatment cycles was 5 (1–31). Median survival time in the matched BSC patients was only 13 months (p=0.01).

Median age in the low-dose cytosine arabinoside group was also 70 years (60–81). Median survival time of patients receiving LD-AraC was 17 months, as compared to 11 months in the group of matched BSC patients (p=n.s.).

The median age in the induction chemotherapy group was 67 years (60–78) and the median survival 21 months, as compared to 16 months in the matched BSC patients (p=n.s).

This data confirms that high-risk MDS patients derive a substantial survival benefit from treatment with hypomethylating agents as compared to best supportive care. The results of our retrospective matched-pairs analysis are in remarkable agreement with a large prospective clinical trial (AZA-001, Fenaux et al., Lancet Oncogy 2009) that yielded a benefit in median overall survival of 24.4 vs. 15 months for 5-Aza vs. conventional care regimens (BSC, LD-AraC, induction CTx), and a benefit of 21.1 vs. 11.5 months in a subgroup analysis of 5-Aza vs. BSC. We observed no significant survival benefit for patients treated with LD-AraC or induction chemotherapy, as compared with BSC. Accordingly, hypomethylating agents should be considered treatment of choice in elderly high-risk MDS patients who are not candidates for allogeneic stem cell transplantation.

Gattermann:Novartis, Celgene: Honoraria, Participation in Advisory Boards on deferasirox clinical trials, Research Funding. Germing:Novartis, Celgene: Honoraria, Research Funding. Kuendgen:Celgene: Honoraria.