An IPSS-R Cutpoint of 3 Stratified Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML) Patients (pts) into Two Risk Groups

Introduction

The Revised International Prognostic Scoring System (IPSS-R) has refined the prognostic stratification of MDS by defining five risk groups categories, including the novel intermediate group when the score ranges from 3.5 to 4.5. For therapeutic decisions, pts in clinical practice tend to be categorized into low and high risk, although the exact cutpoint outlining these categories in the IPSS-R setting has not been established. The aim of the study is to stratify MDS and CMML pts in low vs. high risk pts according to the IPPS-R score.

Methods

Four-hundred forty six pts consecutively diagnosed with MDS and CMML according to the WHO 2008 classification between 2011 and 2016 in two University hospitals (Vall d´Hebron and Institut Català d´Oncologia) were included. MDS pts were stratified according to the IPSS and IPSS-R, whereas CMML pts were stratified according to the IPSS-R and CMML Prognostic Scoring System (CPSS). The cutpoint was obtained by the inference procedure of Contal and O´Quigley (Contal et al., CSDA 1999) based on the log-rank statistic test. Chi-squared test and Student's t test or Mann-Whitney was used for categorical and continuous variables, respectively. Survival analysis was calculated using the Kaplan-Meier method and log-rank test was used for statistical comparison. Statistical analysis was performed using the R version 3.3.1.

Results

Three hundred and sixty-four pts were diagnosed with MDS and 82 with CMML. The main characteristics of the pts are detailed in tables 1 and 2. Among MDS pts, median follow-up for survivors was 37 months (range 30.8-41.8 months). At the last follow-up, 146 (42%) pts have died and the median OS was 40.2 months (CI95% 34.2-50.4 months). As per the CMML pts, median follow-up for survivors was 26.4 months (range 23-49.7), at the last follow-up 46 (58%) pts have died, and the median OS was 31 months (CI95% 34.2-52.8).

On the basis of the log-Rank statistic test, the IPSS-R score of ≤3 vs . >3 points was the cutpoint that better dichotomizes pts into 2 risk categories, lower-risk vs. higher-risk, providing statistically significant differences in OS in both MDS and CMML pts (Figure 1 and 2). According to this categorization, 249 (68%) and 115 (32%) MDS pts were classified as low and high risk, exhibiting an OS of 61.1 months (CI95% 46.6-NA) vs . 13.9 months (CI95% 10.6-19.2), respectively (HR= 3.85, CI95% 2.7-5.3; p=0.001). In the CMML subgroup according to this categorization, 71 (87%) and 11 (13%) patients were classified as low and high risk, with an OS of 31.4 months (CI95% 25.5-NA) vs. 15 months (CI95% 3.9-NA), respectively (HR= 3.33, CI95% 1.5-7.4; p=0.001). (Figure 1 and 2) Interestingly, all pts included in the intermediate IPSS-R group fall into the high-risk category according to this cutpoint.

In the univariate analysis comparing the main characteristics between low and high risk using the cutpoint of 3, the following variables were statistically significant: age, WHO classification, laboratory data (hemoglobin <10 g/dl, neutrophils <0.5 x10⁹/L and platelets 30 x10⁹/L), IPSS, IPSS-R, and IPSS-R cytogenetic categories (Table 1 and 2) In the multivariate analysis, hemoglobin <10 g/dl, blast <5% and IPSS-R cytogenetics categories very low and low retained their statistical significance.

Conclusions

An IPSS-R cutpoint of 3 proved to be useful in the clinical setting to stratify MDS and CMML patients into low and high risk groups with significant differences in OS. Furthermore, this cutpoint includes the intermediate risk IPSS-R group within the high risk pts, which may have clinical implications in the daily management of these patients.