Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents

Purpose Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Second-line treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively ( P = .05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively ( P = .21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.

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Efficacy of granulocyte colony stimulating factor in combination with erythropoiesis stimulating agents for treatment of anemia in patients with lower risk myelodysplastic syndromes: A systematic review

Critical Reviews in Oncology/Hematology ◽

10.1016/j.critrevonc.2019.01.021 ◽

2019 ◽

Vol 136 ◽

pp. 37-47 ◽

Cited By ~ 3

Author(s):

Lucas Affentranger ◽

Julia Bohlius ◽

Mahmoud Hallal ◽

Nicolas Bonadies

Keyword(s):

Systematic Review ◽

Myelodysplastic Syndromes ◽

Lower Risk ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Erythropoiesis Stimulating Agents ◽

Stimulating Factor

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Long-term outcome of anemic lower-risk myelodysplastic syndromes without 5q deletion refractory to or relapsing after erythropoiesis-stimulating agents

Leukemia ◽

10.1038/leu.2013.16 ◽

2013 ◽

Vol 27 (6) ◽

pp. 1283-1290 ◽

Cited By ~ 45

Author(s):

C Kelaidi ◽

◽

S Park ◽

R Sapena ◽

O Beyne-Rauzy ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Lower Risk ◽

Term Outcome ◽

Long Term Outcome ◽

Erythropoiesis Stimulating Agents ◽

5Q Deletion

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Outcome of Lower-Risk Patients with Myelodysplastic Syndromes without 5Q Deletion after Failure of Erythropoiesis Stimulating Agents

Leukemia Research ◽

10.1016/s0145-2126(17)30162-5 ◽

2017 ◽

Vol 55 ◽

pp. S33 ◽

Cited By ~ 1

Author(s):

S. Park ◽

J.F. Hamel ◽

A. Toma ◽

C. Kelaidi ◽

S. Thepot ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Lower Risk ◽

Erythropoiesis Stimulating Agents ◽

Risk Patients ◽

5Q Deletion

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Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents

Journal of Clinical Oncology ◽

10.1200/jco.2015.66.0118 ◽

2016 ◽

Vol 34 (25) ◽

pp. 2988-2996 ◽

Cited By ~ 104

Author(s):

Valeria Santini ◽

Antonio Almeida ◽

Aristoteles Giagounidis ◽

Stefanie Gröpper ◽

Anna Jonasova ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Lower Risk ◽

Phase Iii ◽

International Prognostic Scoring System ◽

Double Blind Study ◽

Double Blind ◽

Erythropoiesis Stimulating Agents ◽

Endogenous Erythropoietin ◽

Erythroid Response ◽

Rbc Transfusion

Purpose This international phase III, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of lenalidomide in RBC transfusion–dependent patients with International Prognostic Scoring System lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Patients and Methods In total, 239 patients were randomly assigned (2:1) to treatment with lenalidomide (n = 160) or placebo (n = 79) once per day (on 28-day cycles). The primary end point was the rate of RBC transfusion independence (TI) ≥ 8 weeks. Secondary end points were RBC-TI ≥ 24 weeks, duration of RBC-TI, erythroid response, health-related quality of life (HRQoL), and safety. Results RBC-TI ≥ 8 weeks was achieved in 26.9% and 2.5% of patients in the lenalidomide and placebo groups, respectively (P < .001). Ninety percent of patients achieving RBC-TI responded within 16 weeks of treatment. Median duration of RBC-TI with lenalidomide was 30.9 weeks (95% CI, 20.7 to 59.1). Transfusion reduction of ≥ 4 units packed RBCs, on the basis of a 112-day assessment, was 21.8% in the lenalidomide group and 0% in the placebo group. Higher response rates were observed in patients with lower baseline endogenous erythropoietin ≤ 500 mU/mL (34.0% v 15.5% for > 500 mU/mL). At week 12, mean changes in HRQoL scores from baseline did not differ significantly between treatment groups, which suggests that lenalidomide did not adversely affect HRQoL. Achievement of RBC-TI ≥ 8 weeks was associated with significant improvements in HRQoL (P < .01). The most common treatment-emergent adverse events were neutropenia and thrombocytopenia. Conclusion Lenalidomide yields sustained RBC-TI in 26.9% of RBC transfusion–dependent patients with lower-risk non-del(5q) myelodysplastic syndromes ineligible for or refractory to erythropoiesis-stimulating agents. Response to lenalidomide was associated with improved HRQoL. Treatment-emergent adverse event data were consistent with the known safety profile of lenalidomide.

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