Polish experience of lenalidomide in the treatment of lower risk myelodysplastic syndrome with isolated del(5q)

Abstract

BackgroundLenalidomide has been approved for the treatment of lower-risk myelodysplastic syndrome (MDS) with 5q deletion (del(5q)). We present for the first time a retrospective analysis of low-risk MDS with isolated del5q treated with lenalidomide, outside the clinical trials.Methods36 red blood cell (RBC) transfusion-dependent patients have been included in the study. Patients received lenalidomide 10 mg/day on days 1–21 of 28-day cycles.Results91.7 % of patients responded to lenalidomide treatment: 72.2 % achieved erythroid response, 19.4 % achieved minor erythroid response and 8.4 % of patients did not respond to treatment. Response depended on number of previous treatment lines (p = 0.0101), International Prognostic System Score (IPSS; p = 0.0067) and RBC transfusion frequency (p = 0.0139). Median duration of response was 16 months (range 6–60 months). Treatment was well tolerated. We observed hematological toxicity (grade 3 and 4): neutropenia in 16 (44.4 %) patients and thrombocytopenia in 9 (25 %) patients. Two patients (5.5 %) progressed to high-risk MDS and two subsequent progressed to acute myeloid leukemia. A Kaplan-Meier estimate for overall survival at 5 years in the study group was 79.0 ± 8.8 %.ConclusionsLenalidomide in this group of patients was beneficial for the treatment of RBC transfusion-dependency with well-known safety profile.

Efficacy and Safety of Lenalidomide for Treatment of Low-/Intermediate-1-Risk Myelodysplastic Syndromes with or without 5q Deletion: A Systematic Review and Meta-Analysis

“…The overall rates of HI-E were presented in twelve articles [15,18,20–26,28–30]. High heterogeneity of the overall rate of HI-E was found from the data ( P < 0.001, I 2 = 97.0%), and thus the random-effect model was chosen.…”

“…AEs of lenalidomide and relevant data were presented in ten articles [14,15,18,20,21,23–26,30]. All studies investigated the incidences of grades 3–4 AEs.…”

“…Based on the analysis of pooled data, the incidence rates of neutropenia and thrombocytopenia were obviously high and the RR of grades 3–4 neutropenia and thrombocytopenia was higher in the lenalidomide-treated group. The survival time was longer in the group of patients with grades 3–4 AEs because the erythroid and cytogenetic responses occurred after the treatment of lenalidomide[26]. Therefore, lenalidomide could be safely used to treat lower-risk MDS patients.…”

Bone Marrow Conventional Karyotyping and Fluorescence In Situ Hybridization

“…2,[16][17][18][19][20][21] The discovery of lenalidomide as an effective treatment in patients with a del(5q) abnormality has further cemented the role of genetic studies in the diagnosis and treatment of the patient with MDS. [22][23][24][25] Recent studies in MDS have shown frequent somatic mutations in the spliceosomal machinery (eg, SFB31, SRSF2, U2AF1, ZRSR2), epigenetic modifiers (eg, TET2, DNMT3A, IDH2/1, EZH2, ASXL1), signaling transducer, transcription factors, and other important gene targets (eg, RUNX1, TP53, NRAS, STAG2, CBL, ETV6). [3][4][5][6][7][8] This molecular information has exhibited value in refining the MDS prognostic risk stratification scheme and may improve therapy response prediction and choice of potential targeted therapies.…”

Techniques for detecting chromosomal aberrations in myelodysplastic syndromes

“…Moreover, selection of particular treatment may rely on the presence of specific chromosomal aberrations. Low-risk, transfusion-dependent MDS patients with del(5q) are reported to respond well to lenalidomide [ 28 – 30 ]. So accurate detection of del(5q) is not only important for precise diagnosis of MDS, but also vital for individualized treatment of MDS patients.…”