Background: MDSs are clonal hematopoietic stem cell malignancies characterized by cytopenias resulting from ineffective hematopoiesis. A phase 2 study of lenalidomide (MDS-002) demonstrated hematological improvement in patients with MDS without an associated deletion 5q cytogenetic abnormality (

List AF, et al. Haematologica 2006;91[suppl1]:379[abst 1032]
). We now report multicenter results after 〉2 yrs follow-up.

Methods: A total of 214 pts with transfusion-dependent anemia were categorized into the following IPSS MDS risk groups after central review of bone marrow morphology, karyotype, and peripheral blood findings: Low/Int-1 (168 [78%]); Int-2/High (8 [4%]); and unclassified (38 [18%]). Patients were unclassified for missing or inadequate marrow studies for central review (morphology [29] or cytogenetic [7]) or other diagnoses (AML [1], atypical CML [1]). Patients were evaluated for frequency and duration of red blood cell transfusion independence (RBC-TI) (IWG criteria), hemoglobin (Hgb) response, and safety. The starting dose of lenalidomide was 10 mg (daily or daily × 3 wks q28d cycle).

Results: Overall, 56 (26%) of 214 enrolled patients achieved RBC-TI. Median time to RBC-TI was 5 wks, median duration of RBC-TI response was 41.0 wks (range, 8.0–136.4), and median Hgb increase achieved during RBC-TI was 3.2 g/dL (range, 1.0–9.8). An additional 36 patients experienced a ≥ 50% reduction in RBC transfusions (overall hematological improvement in 92 [43%] patients). Overall, 47 (22%) patients had an abnormal karyotype at baseline and 9 (19%) patients achieved a cytogenetic response (4 complete). The most common drug-related grade 3/4 adverse events (AEs) were neutropenia and thrombocytopenia (25% and 20%, respectively). Deep vein thrombosis occurred in only 2 (1%) patients. The duration of RBC-TI was ≥ 52 weeks in 21 (38%) patients. Among these 21 patients, 14 (67%) did not require a lenalidomide dose reduction during the first 52 weeks of treatment. Analyses of response variables will be presented. Dose-limiting neutropenia/thrombocytopenia was not reported after 52 weeks. The most commonly reported AEs after 52 weeks were mild-moderate diarrhea and fatigue (38% and 29%, respectively).

Conclusion: Lenalidomide is an active, well-tolerated treatment in MDS patients with transfusion-dependent anemia that is not associated with a deletion 5q abnormality. The rate of erythroid hematologic improvement and duration of RBC-TI is encouraging and offers a possible alternative to cytokine therapy.

Topics:
chromosome abnormality, lenalidomide, myelodysplastic syndrome, hemoglobin, anemia, erythrocyte transfusion, karyotype determination procedure, neutropenia, thrombocytopenia, transfusion

Disclosures: Revlimid (lenalidomide) is indicated for the treatment of patients with transfusion-dependent anemia due to Low-or Intermediate-1 - risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. This abstract pertains to a study being conducted in patients with transfusion-dependent anemia due to Low- or Intermediate-1 - risk myelodysplastic syndromes associated without a deletion 5q cytogenetic abnormality.; JZ, RK, KW, MS are employees of Celgene.; GD, AL, PG, JB, CS have consulted in the past two years.; JZ, RK, KW, MS, CS own shares in a publicly traded company.; VK, EF, AL, PG, CS, JS, LD, and JR have received research funding.; AR, JB and PG have received honoraria from an entity.; JZ as the Chief Medical Officer of Celgene has given expert testimony to a variety of legal and financial fora.; AL, AR, JB, PG, CS participated in Speakers Bureau and or Advisory Committees.

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2006, The American Society of Hematology
2006
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