Validation of the IPSS-R in lenalidomide-treated, lower-risk myelodysplastic syndrome patients with del(5q)
Authors: M A Sekeres, A S Swern, P Fenaux, P L Greenberg, G F Sanz, J M Bennett, F Dreyfus, A F List, J S Li, M M Sugrue
Journal: Blood Cancer Journal (2014)

2][3][4] The International Prognostic Scoring System (IPSS) categorizes untreated MDS patients into one of four risk groups (low, intermediate [Int]-1, Int-2 and high) based on the percentage of bone marrow blasts, presence of cytogenetic abnormalities and number of cytopenias. 2 The revised IPSS (IPSS-R), also developed in untreated MDS patients, refines risk group definitions by assigning greater weight to the cytogenetic risk categories, 5 the depth of cytopenias and by altering bone marrow blast percentage cutoff points. 68][9] The prognostic value of the IPSS-R in treated patients has not been fully established, [8][9][10][11] and its prognostic value specifically in patients with deletion 5q [del(5q)] treated with lenalidomide is unknown.We assessed the prognostic value of IPSS-R using data from two multicenter studies (MDS-003 12 and MDS-004 13 ) that evaluated lenalidomide in red blood cell (RBC) transfusion-dependent patients with IPSS-defined low-or Int-1-risk MDS and del(5q), with or without additional chromosomal abnormalities.Methods for the MDS-003 and MDS-004 studies have been previously described; 12,13 both studies were sufficiently similar to justify combined analyses.Patients received lenalidomide at doses of 5 or 10 mg/day for 28 days of each 28-day cycle, or 10 mg/day for 21 days of each 28-day cycle.This analysis included patients from MDS-003 and MDS-004 with available baseline IPSS2 and IPSS-R 6 scores, who received lenalidomide from study start.IPSS-R adjusted for age (IPSS-R-A) was also calculated. 6Risk groups with o5 patients were excluded.End points included overall survival (OS), time to progression to acute myeloid leukemia (AML) and rate of RBC transfusion independence (RBC-TI) ⩾ 26 weeks.AML was defined by French-American-British criteria. 1OS and time to AML were estimated using the Kaplan-Meier method, with differences evaluated using the log-rank test.Rates of RBC-TI ⩾ 26 weeks were compared across risk groups using the Cochran-Armitage trend test.Univariate and multivariate Cox proportional hazards models were developed using the following covariates: IPSS (low-risk vs Int-1-risk), IPSS-R (multi-level), gender (female vs male), age (per year increase), French-American-British classification (refractory anemia (RA)/RA with ringed sideroblasts vs RA with excess blasts/chronic myelomonocytic leukemia), time since diagnosis (per year increase), transfusion burden (units/ 8 weeks), bone marrow blast count (as a continuous variable), bone marrow blasts (o 5% vs ⩾ 5%), number of cytopenias (as a continuous variable), number of cytopenias (0-1 vs 2-3), platelet count, absolute neutrophil count, hemoglobin (each analyzed as a continuous variable), del(5q) status (isolated vs ⩾ 1 additional abnormalities), RBC-TI ⩾ 26 weeks response (yes vs no), RBC-TI ⩾ 26 weeks response (time-varying; yes vs no), serum ferritin (per log unit increase) and serum lactate dehydrogenase (per unit increase).Significant variables identified by univariate analysis