Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS

Abstract

Lenalidomide is the approved treatment for patients with red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndromes (MDS) and chromosome 5q deletion (del(5q)). We report the long-term outcomes (median follow-up 3.2 years) in patients treated with lenalidomide in the MDS-003 trial. RBC transfusion independence (TI) ≥ 8 weeks was achieved in 97 of 148 treated patients (65.5%), with a median response duration of 2.2 years. Partial or complete cytogenetic response was achieved by 63 of 88 evaluable patients (71.6%). Median overall survival (OS) was longer in patients achieving RBC-TI ≥ 8 weeks (4.3 vs 2.0 years in non-responders; P<0.0001) or cytogenetic response (4.9 vs 3.1 years in non-responders; P=0.010). Time to acute myeloid leukemia (AML) progression was longer in patients achieving RBC-TI ≥ 8 weeks or any cytogenetic response versus non-responders (P=0.001 and P=0.0002, respectively). In a landmark multivariate analysis, RBC-TI ≥ 8 weeks was associated with prolonged OS (P<0.001) and a trend toward reduced relative risk of AML progression (P=0.080). Among these lower-risk MDS patients with del(5q), lenalidomide was associated with prolonged RBC-TI and cytogenetic responses, which were linked to improved OS and reduced risk of AML progression.

Figure 1

Duration of red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response to lenalidomide in: (a) the overall population; (b) by baseline karyotype and (c) by cytogenetic response. Symbols indicate censored patients who remain transfusion independent at the time of data cutoff or at the time of study discontinuation. Abbreviation: del(5q), chromosome 5q deletion.

Figure 2

Kaplan–Meier estimates of overall survival according to: (a) baseline karyotype (1 patient had no baseline karyotype available and was excluded from the analysis); (b) red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response (by the 6-month landmark analysis) and (c) partial or complete cytogenetic response (by the 6-month landmark analysis). Abbreviation: del(5q), chromosome 5q deletion.

Figure 3

Time to acute myeloid leukemia (AML) progression with death as a competing risk according to: (a) baseline karyotype (one patient had no baseline karyotype available and was excluded from the analysis); (b) red blood cell-transfusion independence (RBC-TI) ⩾8 weeks response and (c) partial or complete cytogenetic response. Symbols indicate censored patients (+) or patients who died without AML (∘). Abbreviation: del(5q), chromosome 5q deletion.