Myelodysplastic syndromes (MDS) comprise a heterogeneous group of hematopoietic stem cell disorders characterized by dysplasia resulting in cytopenia in one or more cell lineages. Th e World Health Organization (WHO) classifi cation recognizes MDS associated with an isolated partial deletion of the long arm of chromosome 5 [del(5q)] as a distinct entity. Th e so-called del(5q) syndrome is characterized by macrocytic anemia, with or without other cytopenias, and less than 5% blasts in the bone marrow. Treatment of MDS consists traditionally of red blood cell (RBC) transfusions. In 2005 the Food and Drug Administration approved lenalidomide for the treatment of RBC transfusion-dependent MDS with del(5q). In Europe, lenalidomide is not yet approved for the treatment of patients with MDS and del(5q).Th e mechanisms of action include direct anti-tumor activity (e.g. via secreted protein acidic and rich in cysteine [SPARC], inhibitory eff ects on cdc25c and pp2ac and others), inhibition of angiogenesis and immune modulation [1,2]. Patients with del(5q) who respond to therapy with lenalidomide benefi t from improvement of anemia and transfusion independence, as shown in the MDS001 and MDS003 trials [3,4]. Recently, the French named patient program (NPP) and MDS004 trial confi rmed the high rate of transfusion independence upon treatment with lenalidomide in MDS with del(5q) [5,6]. In this study, we describe the evaluation of the fi rst Dutch NPP, investigating the effi cacy of lenalidomide in patients with MDS and del(5q).Patients were eligible for inclusion if diagnosed with MDS and del(5q), with or without additional cytogenetic abnormalities. Between 2007 and 2009, 40 patients were enrolled in the program after informed consent, in accordance with the Declaration of Helsinki. Case report forms could not be retrieved from 13 patients. Diagnoses were made using the WHO 2001 classifi cation. Karyotypes were examined and described according to the International System for Human Cytogenetic Nomenclature guidelines [7]. If conventional karyotyping failed due to lack of metaphases, a fl uorescence in situ hybridization (FISH) procedure was performed. Eight patients were excluded: one patient had a duplicate identity, fi ve patients had a normal karyotype at baseline and two patients received lenalidomide for less than 1 month. Among the 19 patients that could be evaluated, two patients were already receiving lenalidomide treatment in the context of the MDS004 trial. Both patients were included and continued treatment in the Dutch NPP after termination of the MDS004 trial. Patients received lenalidomide at a daily dose of 10 mg or 5 mg for every 21 days or continuously on a 28-day cycle. Th e dose and schedule were adjusted based on drug toxicity and blood counts according to standard guidelines. Response was evaluated using the International Working Group (IWG) 2006 response criteria [8]. Th e endpoints were disease status, hematologic improvement and cytogenetic response. Response was categorized as complete remission (CR)...
5032 Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplasia and cytopenia in one or more cell lineages. The WHO2001 classification recognizes MDS associated with del (5q) as a distinct entity. Previous data have shown that Lenalidomide can reduce transfusion requirements and reverse cytological and cytogenetic abnormalities in patients with MDS and del (5q). In this study we aimed to evaluate the efficacy of Lenalidomide in MDS patients with a del (5q) cytogenetic abnormality. Patients were eligible for inclusion if they had a chromosome 5q deletion with or without additional cytogenetic abnormalities. Between 2007 and 2009, 19 patients after signing informed consent were eligible for response in this patient named program. According to the WHO2001 classification the diagnoses were RCMD (n = 6), RAEB-1 (n = 3), RAEB-II (n = 2) and 5q-syndrome (n = 8). The median age was 68 [range 53 – 85]. At baseline 13 patients had an isolated del (5q), 3 patients had 1 additional cytogenetic abnormality and 3 patients had more than 1 additional cytogenetic abnormality. Patients received Lenalidomide at a daily dose of 10 mg for 21 days of a 28 days cycle. The dose and schedule were adjusted based on drug toxicity and blood count. Response was evaluated using the IWG2006 response criteria (Cheson et al, Blood 2006). Two patients stopped Lenalidomide treatment due to drug toxicity before completion of the first cycle. According to the IWG2006 criteria, 7 patients showed a complete remission (CR), 7 stable disease (SD) and 3 patients showed disease progression (PD) under treatment. Patients with a CR showed a significantly better overall survival (OS) (median 37.9 weeks, range 17.7 – 40.3 weeks ) compared to patients with SD (median 17.6 weeks, range 7.7 – 33.9 weeks) and PD (median 8.8 weeks, range 8.8 – 13.7) groups (p = 0.007). From the patients with CR and cytogenetic evaluation during follow up, five had a complete cytogenetic response. Median pre-treatment Hb was 5.3 mmol/L [range 4.3 – 6.9], absolute neutrophil count (ANC) 1.45×10̂9/L [range 0.40 – 11.36] and thrombocytes 218.5×10̂9/L [range 38 – 902]. Erythroid response (HI-E) was achieved in 11 patients after a median of 2.5 cycles [range 2 – 4] and sustained for 8 cycles [range 3 – 16]. Patients that achieved HI-E showed a significant increase in Hb (median 7.0 mmol/L, p < 0.001), the non-responders a stable Hb (median 5.1 mmol/L, p = 0.3661). Achievement of HI-E was significantly associated with improved OS (p = 0.02). Neutrophil response could be evaluated in 2 patients because the pre-treatment ANC was normal (ANC ≥ 1×10̂9/L) for the majority of the patients. One patient with pre-treatment ANC of 0.4×10̂9/L responded after 1 cycle (ANC 1.2×10̂9/L) and response was sustained for 11 cycles. Platelet response could be evaluated in 5 patients with pre-treatment platelets of <100×10̂9/L. Two patients showed a platelet response for a median duration of 6 cycles [range 3 – 9]. Fourteen patients stopped Lenalidomide treatment after a median of 60.7 weeks [range 10 – 182 weeks]. Six patients stopped due to lack of response, 2 patients due to toxicity, 3 patients due to disease progression, 2 patients stopped treatment after loss of response and 1 patient stopped after obtaining complete remission. In conclusion, patients that achieved CR had a significantly better OS compared to SD and PD patients. Moreover, the majority of patients who achieved HI-E had a significantly improved OS compared with patients without HI-E (p = 0.02), regardless of achievement of a CR. Our results confirm that Lenalidomide can reduce transfusion requirements and reverse cytological and cytogenetic abnormalities in patients with MDS and a del (5q) cytogenetic abnormality. Disclosures: No relevant conflicts of interest to declare.
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