Outcome of Patients with Myelodysplastic Syndrome (MDS) with Bone Marrow (BM) Blasts Between 10 to 30% Treated with Hypomethylating Agents Versus Intensive Chemotherapy

In 2001, the World Health Organization modified the French-American-British (FAB) classification for MDS by folding the refractory anemia with excess blasts in transformation (RAEB-t) category into acute myeloid leukemia (AML). Since then, controversy exists regarding whether this subset of pts should be treated with AML (ie cytotoxic therapy) or MDS therapy (hypomethylating agents, HMA). Furthermore, a subset analysis of the AZA-001 trial has shown that azacitidine prolongs overall survival (OS) compared to intensive chemotherapy (IC) in pts with AML and BM blasts of 20–30%. The purpose of this analysis is to evaluate the clinical outcome and OS of pts with MDS and BM blasts between 10–30% who were treated with HMA vs IC.

We conducted a retrospective analysis of newly diagnosed pts with refractory anemia with excess blasts-2 (RAEB-2) and RAEB-t according to FAB classification criteria that were treated at one institution with frontline therapy between 1/2000 and 10/2011. For the purpose of this analysis, pts were divided into 4 groups based on their treatment: 1) hypomethylating agents (HMA) only (azacitidine and decitabine), 2) hypomethylating agents in combination with investigational drug (HMA-I), 3) intensive chemotherapy (IC, mainly cytarabine based regimens), and 4) investigational agents (I-A). Responses were defined as achieving a complete remission (CR), complete remission without platelet recovery (CRp), or complete remission with incomplete recovery (CRi) as defined by the International Working Group criteria (Cheason BD, J Clin Oncol. 2003). OS was calculated by using the Kaplan-Meier method, and survival curves were compared by using the log-rank test. The Gehan-Wilcoxon method was used to evaluate OS at early time point.

Three hundred forty-nine pts were included in the final analysis. 53 pts (15%) were treated with HMA, 40 pts (11%) with HMA-I, 237 pts (68%) with IC, and 19 pts (5%) with I-A. Pts' clinical characteristics are summarized in table 1. 20 pts (38%) achieved a response in HMA group, 19 (48%) in HMA-I, 143 (60%) in IC, and 1 (5%) in I-A group (P <0. 001). Response duration was 19. 3 months (m), 14. 7 m, 14. 5 m, and not reached, respectively, (P = 0. 62). 4 weeks mortality was 1 (2%), 2 (5%), 10 (4%) and 2 (11%) respectively, (P = 0. 36). With a median follow up of 37 m (1–96), the median OS was 21. 8 m, 16. 1 m, 14. 6 m, and 15. 8 respectively, (P = 0. 15). The OS was higher in pts who were treated with HMA vs IC by using Gehan-Wilcoxon test (P = 0. 04). In subgroup analysis, pts with BM blasts between 20–30% had higher response rates when they were treated with IC (63%) compared to HMA (44%), HMA-I (38%), and I-A (13%), (P = 0. 008); however, the remission duration 16 m, not reached, 15 m, and 8 m, respectively, (P = 0. 28), and the OS 16 m, 27 m, 24 m, and 8 m respectively, (P = 0. 2) were not significant.

Although pts with MDS and BM blasts between 10–30% achieved higher response rates when they treated with IC vs HMA, pts with BM blasts between 20–30% had similar OS when they were treated with HMA vs IC. There was a trend toward increased survival early after treatment administration in favor of HMA. This data suggests that IC is not superior to HMA in the treatment of this subgroup of pts.

No relevant conflicts of interest to declare.