Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: a subset analysis from the MDS-004 study

Abstract

Objective: A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q).

Methods: Patients received lenalidomide 10 mg/d (days 1-21; n = 47) or 5 mg/d (days 1-28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively.

Results: Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3-4 adverse event was myelosuppression.

Conclusions: These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q).

Keywords: acute myeloid leukaemia; del(5q); lenalidomide; myelodysplastic syndromes; transfusion independence.

Figure 1

Mean change (±standard deviation) in haemoglobin levels from baseline over time by randomised treatment group in patients with isolated del(5q) (intent-to-treat population). *One of the 47 patients in the LEN 10 mg group was excluded due to lack of haemoglobin values at baseline and postbaseline. LEN, lenalidomide.

Figure 2

Progression to AML in patients with isolated del(5q) (intent-to-treat population) by: (A) randomised treatment group; (B) 6-month landmark analysis according to RBC-TI ≥182 d; and (C) cytogenetic response (major + minor response). *Of the 43 patients randomised to LEN 5 mg, 25 crossed over to LEN 10 mg in the open-label extension phase. ^†Of the 45 patients randomised to placebo, 38 crossed over to LEN 5 mg in the open-label extension phase. AML, acute myeloid leukaemia; LEN, lenalidomide; RBC-TI, red blood cell-transfusion independence.

Figure 3

Overall survival in patients with isolated del(5q) (intent-to-treat population) by: (A) randomised treatment group; (B) 6-month landmark analysis according to RBC-TI ≥182 d; and (C) cytogenetic response (major + minor response). *Of the 43 patients randomised to LEN 5 mg, 25 crossed over to LEN 10 mg in the open-label extension phase. ^†Of the 45 patients randomised to placebo, 38 crossed over to LEN 5 mg in the open-label extension phase. LEN, lenalidomide; RBC-TI, red blood cell-transfusion independence.