Outcome of Patients (pts) with Low and Intermediate-1 Risk Myelodysplastic Syndrome (MDS) After Hypomethylating Agent (HMA) Failure.

Abstract

AbstractAbstract 2824 Background:HMA are standard of care in pts with high-risk MDS and commonly used in pts with lower risk. Pts with high-risk disease post HMA failure have a poor prognosis with a median survival of 4 months (Jabbour et al. Cancer. 2010;116:3830–4). The prognosis of patients with low and intermediate-1 risk MDS after HMA failure is not known. Aims:To assess survival in patients with low and intermediate-1 risk disease at the time of HMA failure that might benefit from specific strategies or investigational agents. Methods:Data from 699 patients with MDS (n=397) and chronic myelomonocytic leukemia (n=302) treated with HMA at one institution between 2000 and 2011 were reviewed. 126 (18%) of them were of low and intermediate-1 risk disease by IPSS score. Results:A total of 30 (24%) patients with MDS (n=26) and CMML (n=4) who had failed HMA therapy and remained of low and intermediate-1 risk disease were analyzed. These included 6 patients with low- and 24 intermediate-1 risk disease. Eleven patients had secondary disease. At the start of HMA, 22 patients were low-risk and 8 were intermediate-1 risk disease. Seventeen patients had a diploid cytogenetic analysis. Seven and 23 patients received azacitidine and decitabine, respectively. These patients had discontinued HMA because of primary resistance in all patients. The characteristics of the study group are shown in Table 1.Upon HMA failure, 24 (80%) were low-risk disease and 6 (20%) intermediate-1-risk disease. A total of five (17%) patients transformed subsequently into acute myeloid leukemia. After a median of 18 months from HMA failure, 12 (40%) patients remained alive. The median overall survival was 22 months with estimated 1- and 2-year overall survival rates of 65% and 45%, respectively. Considering overall survival from the start of HMA therapy, the median survival was 29.5 months with estimated 1- and 2-year overall survival rates of 80% and 60%, respectively. The 30 patients with HMA failure were subsequently assessed by the lower-risk MDACC risk model (Garcia-Manero et al. Leukemia. 2008;22:538–43): 8 (27%) had low-risk, 8 (27%) intermediate-risk, and 14 (46%) high-risk disease. Their 1-year survival rates were 66%, 73%, and 86%, respectively. Considering survival from the time of the initiation of HMA therapy, the estimated 1-year survival rates were 60%, 70%, and 100%, respectively, for patients with high-risk, intermediate-risk, and low-risk disease according to the MDACC risk model. After HMA failure, 11 (37%) patients received salvage investigational therapy, of whom 3 responded with 2 achieving hematologic improvement for a median of 12 months (range, 5–19) and one patient achieving a complete remission for 14 months that was lost thereafter, 1 (3%) received immunotherapy, 1 (3%) received growth factors only, and 17 (57%) elected not to receive any further treatment. No response was observed in the 2 patients who received subsequent immunotherapy or growth factors. Conclusion:The outcome of patients with low and intermediate-1 risk MDS after HMA failure is poor and appears to be predictable.Table 1Characteristics at time of failure, N=30N(%) TotalAge ≥ 60 years1963Sex (Male)2377Diagnosis (WHO)RA/MDS-U/RARS/RCMD/RCMD-RS2067RAEB620CMML413IPSSLow620Int-12480CytogeneticDiploid1447Chromosome 5/7 abnormalities13Others1550Hgb < 10g/dL1757PLT < 100 × 109/L2067WBC ≥ 10 × 109/L413ANC < 1.5 × 109/L1653BM blasts percentage0–424805–10620Prior malignancy620Prior chemotherapy310Prior radiation13MDA risk model at initiation of HMALow723Int-11344High1033MDA risk mode at HMA failureLow827Int-1827High1446 Disclosures:Ravandi:Genzyme/Sanofi: Honoraria. Faderl:Genzyme: Advisory Board Other, Research Funding.