Treatment with Lenalidomide in Myelodysplastic Syndromes with 5q Deletion; Results From the Patient Named Program (PNP) in the Netherlands
Authors: Abouyahya Imane , Alhan Canan , Westers Theresia M , Koedam Jan , Ossenkoppele Gert , Van de Loosdrecht Arjan A. 
Published: October 2019

Abstract
Abstract 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.