Lenalidomide Is Likely To Improve Overall Survival in Patients with del(5q) Myelodysplastic Syndrome with a Complex Karyotype.
Authors: Giagounidis Aristoteles A. , Haase Sabine , Germing Ulrich , Göhring-Michaelsen Gundula , Schlegelberger Brigitte , Aul Carlo 
Published: April 2020

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.