Chronic myelomonocytic leukemia (CMML) is a complex clonal hematological disorder classified among myelodysplastic (MDS)/myeloproliferative neoplasms. Prognosis is poor and there is a lack of effective treatments. The hypomethylating agent decitabine has shown activity against MDS and elderly acute myeloid leukemia, but there is little data focusing specifically on its efficacy in CMML. In this prospective, phase 2 Italian study, CMML patients received intravenous decitabine 20 mg/m2 per day on Days 1–5 of a 28-day treatment cycle. Response was evaluated after four and six cycles; patients responding at the end of six cycles could continue treatment with decitabine. Forty-three patients were enrolled; >50% were high-risk according to four CMML-specific scoring systems. In the intent-to-treat population (n=42), the overall response rate after six cycles was 47.6%, with seven complete responses (16.6%), eight marrow responses (19%), one partial response (2.4%) and four hematological improvements (9.5%). After a median follow-up of 51.5 months (range: 44.4–57.2), median overall survival was 17 months, with responders having a significantly longer survival than non-responders (P=0.02). Grade 3/4 anemia, neutropenia and thrombocytopenia occurred in 28.6%, 50% and 38% of patients, respectively. Decitabine appears to be an effective and well-tolerated treatment for patients with high-risk CMML.
Background Erythropoiesis‐stimulating agents effectively improve the hemoglobin levels in a fraction of anemic patients with myelodysplastic syndromes (MDS). Higher doses (HD) of recombinant human erythropoietin (rhEPO) have been proposed to overcome suboptimal response rates observed in MDS patients treated with lower “standard doses” (SD) of rhEPO. However, a direct comparison between the different doses of rhEPO is lacking. Methods A cohort of 104 MDS patients treated with HD was retrospectively compared to 208 patients treated with SD in a propensity score‐matched analysis to evaluate hematological improvement‐erythroid (HI‐E) rate induced by the different doses of rhEPO. The impact of rhEPO doses on survival and progression to leukemia was also investigated. Results Overall HI‐E rate was 52.6%. No difference was observed between different rhEPO doses (P = .28) in matched cohorts; in a subgroup analysis, transfusion‐dependent patients and patients with higher IPSS‐R score obtained a higher HI‐E rate with HD, although without significant impact on overall survival (OS). Achievement of HI‐E resulted in superior OS. At univariate analysis, a higher HI‐E rate was observed in transfusion‐independent patients (P < .001), with a lower IPSS‐R score (P < .001) and lower serum EPO levels (P = .027). Multivariate analysis confirmed that rhEPO doses were not significantly related to HI‐E (P = .26). There was no significant difference in OS or progression to leukemia in patients treated with HD vs SD. Conclusion SD are substantially equally effective to HD to improve anemia and influencing survival in MDS patients stratified according to similar propensity to be exposed to rhEPO treatment.
1702 Background: Prognostic assessment has a crucial role in clinical evaluation of patients (pts) affected by myelodysplastic syndrome (MDS). Recently a Revised International Prognostic Scoring System (IPSS-R) has been developed (Greenberg et al, 2012) to improve the standard IPSS (Greenberg et al, 1997): it identifies five different prognostic categories mainly based on stratification of cytogenetic risk. Another prognostic score proposed in clinical practice is WPSS, based on transfusion dependency and WHO morphologic classification (Malcovati et al, 2005) subsequently modified (rWPSS) introducing level of hemoglobin in lieu of the previous not well defined variable of transfusion dependency (Malcovati et al, 2011). Aims: Aim of our study was to evaluate in a cohort of MDS pts enrolled in the Multiregional Italian MDS Registry the prognostic value of IPSS-R respect to IPSS and compare it with both WPSS and rWPSS. Materials and methods: Among the 1918 MDS pts enrolled in the Multiregional Italian MDS Registry from 1999 to 2012 we excluded all the cases already included in the IWG-PM database that generated the IPSS-R. We thus obtained a cohort of 646 pts with complete follow up. We evaluated the prognostic power of IPSS-R respect to IPSS, WPSS and rWPSS respectively by Harrell's C statistics, analyzing as endpoints overall survival (OS), leukemic evolution (LE) and progression free survival (PFS). For LE we considered leukemic evolution as an event, while all the other causes of death were competing events. For PFS we consider either leukemic evolution or death for any causes as an event. Results: Median age of MDS patients was 75 years (interquartile range: 69–80 years). 378 (59%) out of 646 pts were males. WHO classification was as follows: 33% RCMD, 10% RAEB-1, 9% RAEB-2, 6% CMML, 2% MDS-U, the remaining 40% were RARS, RA, isolated 5q deletion. Median follow up of censored pts was 17 months. According to IPSS score, 47% of pts were low risk, 39% Int-1, 10% Int-2 and 4% high risk. WPSS stratification was as follows: 31% were very low (VL) risk, 37% low (L), 19% intermediate (I), 11% high (H) and 2% very high (VH). By applying rWPSS stratification we obtained 30% VL, 35% L, 17% I, 15% H and 3% VH risk pts. IPSS-R risk stratification was as follows: 20% VL, 46% L, 20% I, 9% H and 5% VH risk pts. OS was analyzed according to the different scores by Kaplan-Meyer method. All prognostic systems allowed the identification of survival curves with significant differences among the different categories of risk stratification. IPSS-R application defined OS curves which better defined patients prognostic categories as shown in fig 1. In fact Harrel's C statistics demonstrated a better predictive value of the IPSS-R respect to IPSS, but also respect to WPSS and rWPSS (C=0,73; 0,63; 0,65; 0,64 respectively). Similar results have been obtained also considering time to LE (fig 2). Harrel's C statistics for LE was 0,84; 0,76; 0,78; 0,77 respectively in IPSS-R, IPSS, WPSS, rWPSS risk stratification groups. Moreover, we analyzed PFS outcomes (fig 3). Also in this case, IPSS-R showed the greatest prognostic power: Harrel's C statistics was 0,76; 0,67; 0,66; 0,69 respectively in IPSS-R, IPSS, WPSS, rWPSS risk stratification groups. Conclusions: In our hands, IPSS-R score demonstrated a better prognostic power respect to previously published prognostic systems (IPSS, WPSS, rWPSS). The cohort of MDS patients we employed to validate the new prognostic scoring system has a short follow up (17 months), due to the exclusion of cases already used to establish the IPSS-R system, and the majority of these are lower risk ones. We can conclude that a careful classification based on cytogenetic examination improve the prognostic power of the score. Thus, IPSS-R is confirmed to be a refined tool, easily applicable in real life and empowered respect to the currently used scores to define MDS patient prognosis. Disclosures: Saglio: Bristol-Myers Squibb: Consultancy, Speakers Bureau.
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