ALBERT

Description: Introduction: Lenalidomide is a novel immunomodulatory drug that is highly effective in patients with transfusion-dependent MDS with del(5q.31) chromosomal abnormality. In the recent MDS-003 study of lenalidomide, there was a 76% erythroid response rate, including 67% transfusion independence. Cytogenetic complexity or bone marrow blast percentage did not affect this response rate. A number of patients experienced disease progression to higher FAB subtypes or AML. We questioned whether lenalidomide might promote disease progression in del(5q) MDS and performed a retrospective analysis to identify risk profiles. Methods: Fifty patients from three institutions were included in this analysis. They were partly treated within the Lenalidomide-MDS003-study. Patients were treated with an initial lenalidomide dose of 10 mg po daily. In case of grade 〉2 neutropenia, G-CSF and antibiotics were administered. Results: The median age was 71 years; 31 patients were female and 20 were male. Disease progression to a higher FAB subtype or to AML occurred in 13 patients (29.5%). 7 of the 13 patients had RAEB at the first lenalidomide dose. In addition, 3 of these had additional chromosomal aberrations (2, trisomy 21; 1, complex karyotype). Of the remaining 6 patients, 2 had a complex karyotype at the first lenalidomide dose, 1 had an additional inv(9)(p11q12), and 1 had hypocellular bone marrow so no FAB subtype could be assigned. Only 2 of 50 patients (4.3%) with 5q-syndrome progressed to AML; both patients developed acute erythroid leukemia (FAB M6). Conclusion: Within the del(5q) MDS subgroup, patients with an isolated del(5q) chromosomal aberration and a bone marrow blast count of 5% bone marrow blasts or additional chromosomal anomalies. Lenalidomide does not seem to increase the risk of transition of del(5q) MDS to higher stages of disease.

Description: Abstract 3807 Poster Board III-743 Background Lenalidomide has high erythroid remitting activity in patients with del(5q) myelodysplastic syndrome (MDS). The actual recommendation is to continue drug administration until relapse of red blood cell transfusion dependence. We address the question whether it is safe and advisable to discontinue lenalidomide after achieving a hematologic and/or cytogenetic response Patients 13 patients (8 female, 5 male) were treated with lenalidomide between December 2003 and January 2007. Median age was 69 years. All had low- or intermediate-1 risk MDS with del(5q) chromosomal abnormality. All patients were red blood cell (RBC) transfusion dependent. All patients started treatment with 5 or 10 mg lenalidomide for 28 out of 28 days or for 21 out of 28 days. Discontinuation of lenalidomide was usually due to patient's choice, and occurred after achievement of RBC transfusion independence. Lenalidomide administration duration ranged from 6 weeks to 24 months Results Four patients had a total lenalidomide exposure of 〉 12 months (12, 15, 18 and 24 months), seven patients between 4 and 12 months and two patients had lenalidomide exposures of 12 months of CCR achievement. They are transfusion independent for 27+ months, 41+ months, and 66+ months. The latter patient had reoccurrence of one metaphase out of 20 with del(5q) after 60 months. Finally, one patient took lenalidomide only six months beyond CCR and remains in transfusion independence for 70+ months. However, this patient was trated with a fludarabine-containing regimen for follicular lymphoma 48 months ago Discussion Discontinuation of lenalidomide seems to be feasible in patients with del(5q) MDS, preferably in those who achieve CCR. Best results regarding long-term transfusion independence and long-term complete cytogenetic remissions are seen in patients who continue lenalidomide for 12 months after CCR achievement. Disclosures: Giagounidis: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Göhring:Celgene Corp.:. Schlegelberger:Celgene Corp.:. Kuendgen:Celgene: Honoraria. Platzbecker:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background: Myelodysplastic syndromes (MDS) with deletion of the long arm of chromosome 5 involving bands q31-q33 (del(5q)) are heterogeneous diseases. While patients with an isolated del(5q) and a low blast count have a long overall survival and a low probability to transform into acute myeloid leukemia (AML), patients with a complex karyotype including del(5q) are threatened by rapid transformation into AML. METHODS: In an analysis of 43 untreated patients with del(5q) and complex karyotypic abnormalities, we show that the median overall survival is 7 months, irrespective of the medullary blast percentage of the patients. We treated 4 patients with del(5q) and a complex karyotypic abnormality with lenalidomide, all of whom had an International Prognostic Scoring System (IPSS) evaluation of intermediate (int)-1 or int-2. The patients were aged 59, 66, 67, and 77 years. 2 were male, two female. MDS diagnosis was made 0.1, 0.2, 0.5, and 1.1 year before treatment commencement. Diagnosis according to World Health Organization classification was RCMD in 2 patients, RCMD-RS, and RAEB-1 (6% medullary blast count). Karyotypes were: 46, XX, del(5)(q15q35), -6, add(17)(p), der(21), +mar; 44, XY, del(5)(q13q33), -7, -15, -18,-19,-19, 3mar; 46, XX, der(1)t(1;2)(p13;?), der(2)t(1;2)(p13;q31), del(2)(p23), del(5)(q15q31); 46, XY, del(5)(q21q34), t(7;10)(q10;q10), add(10)(p12). Treatment was begun with 10 mg orally once a day and dose was reduced in case of adverse events (AE) grade III or IV according to National Cancer Institute (NCI). RESULTS: All four patients are alive 10 months (m), 8 m, 4 m, and 26 m after treatment onset. 2 of the patients achieved complete hematologic and cytogenetic remission of the disease (confirmed by fluorescence in situ hybridization), ongoing for 4+ m and 26+ m. One of the two remaining patients has intermittently had a partial response with transfusion independence for 6 m, but has relapsed requiring 2 packed red cell transfusions every 3 weeks (reduction of 50% to pre-treatment levels). The fourth patient had an increase in platelet counts without other hematologic or cytogenetic response and has interrupted drug intake for 4 m for AE. Drug dose reductions have been done in 2 patients, 1 for pruritus and diarrhea, 1 for lack of appetite. The ongoing responders take 5 mg three times a week (response 26+ m), and 10 mg daily (4+ months). DISCUSSION: Lenalidomide leads to cytogenetic remissions even in high risk MDS with del(5q) and complex karyotypic abnormalities. A long-term complete cytogenetic remission (CCR) exceeding two years has been observed in one of our patients with two follow-up cytogenetic examinations confirming CCR. Another patient has gone into CCR after 6 weeks of treatment on continuous drug treatment. These response patterns suggest the possibility of long-term suppression of the del(5q) clone even in the presence of additional karyotypic abnormalities. While patients with complex karyotypic aberrations including del(5q) rapidly succumb without treatment, lenalidomide may prove to induce long-term remissions in a substantial portion of patients.