Outcome of Patients (pts) with Myelodysplastic Syndrome (MDS) and Chronic Myelomonocytic Leukemia (CMML) Post Decitabine Failure.
Authors: Jabbour Elias , Garcia-Manero Guillermo , Shan Jianqin , O’Brien Susan , Cortes Jorge , Ravandi Farhad , Issa Jean-Pierre J , Kantarjian Hagop M 
Published: April 2020

Abstract
Background and aims: Prognosis in pts with MDS post decitabine failure is reported to be poor, but there are no published data pertaining to survival, particularly in relation to pts who might benefit from specific strategies such as allogeneic stem cell transplantation (SCT) or investigational agents. In this regard, we report the results from our institution.
Materials and Methods: A total of 87 pts with MDS (n=67) and CMML (n=20) after failure of decitabine regimens from 2003 until June 2007 were analyzed. Responses to decitabine and subsequent therapies were coded according to the modified International Working Group criteria (IWG). Acute myeloid leukemia (AML) was defined by 30% or more of bone marrow blasts. Ps were classified according to the IPSS score and the MD Anderson score (MDAS) at the time of start of decitabine therapy and at the time of failure.
Results: Twenty-five (29%) pts had secondary MDS. Among 49 evaluable pts for IPSS risk category at the start of decitabine, 13 (26%) were int-1, 23 (48%) int-2, and 13 (26%) high-risk disease. According to the MDAS, 32 (37%) were high-risk, 31 (36%) int-2, 17 (19%) int-1, and 7 (8%) low-risk disease. Cytogenetics were diploid in 35 (40%) pts; 39 (45%) pts had ≥ 10% bone marrow blasts; 35 (40%) pts had primary resistance to decitabine and 52 (60%) had disease recurrence. Best response to decitabine was complete response (CR) in 21 (24%) pts, partial response (PR) in 2 (2%) pts, a bone marrow CR in 14 (16%) pts, and hematologic improvement (HI) in 14 (16%) pts. The median number of cycles of decitabine administered was 7 (range, 1–20). After a median of 21 months (range, 6 to 39) from decitabine failure, 13 (15%) pts remained alive. The median survival post decitabine failure was 4.3 months; the estimated 12-month survival was 28%. Upon failure, 22 (25%) pts transformed into AML, of whom only 3 were alive. At failure 15 (42%) were high-risk, 15 (42%) were int-2, and 6 (8%) were int-1 among 36 patients assessed for the IPSS score. Among 58 pts assessed by the MDAS, 32 (55%) were high-risk, 17 (29%) int-2, 7 (12%) int-1, and 2 (4%) were low-risk disease. The estimated 12-month survival rates were 27%, 33%, and 33% for respectively, patients with high-risk, int-2, and int-1 risk disease (p=0.99). The 12-month survival rates were 100%, 54%, 41%, and 18% for respectively, pts with low, int-1, int-2, and high-risk disease according to the MDAS (p=0.01). Post decitabine failure, 20 pts received idarubicin and cytarabine (IA); the objective response rate (ORR) was 20%; 39 pts received investigational agents with an ORR of 26%; 5 pts received an allogeneic SCT: 3 achieved and remained in CR. At the last follow-up, 13 pts were alive, 5 in CR post allogeneic SCT in 2, post clofarabine in 1, and post IA in 1, and 1 in marrow CR post IA.
Conclusion: Outcome of pts post decitabine failure is poor with a median survival of 4.3 months. The MDAS can predict survival at the start of decitabine therapy and upon decitabine failure, with patients with low-risk disease having favorable outcome.