Lenalidomide in Myelodysplastic Syndromes with 5q Deletion. Results From the Italian National Cancer Registry

Lenalidomide (LEN) is available in Italy for patients with intermediate-1- and low-risk myelodysplastic syndromes (MDS) associated with 5q deletion (5q-) since October 2008, based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96). LEN is an oncological drug subject to intensive monitoring and, when it is prescribed in MDS, physicians are requested to enter the patient into a registry, which is entirely web-based.

This observational, retrospective, multicenter study (registered at www.clinicaltrials.govasNCT01347944) has enrolled patients at 40 centres of 43 authorized in Italy. The study was approved by the ethic committee of each participating institution. The purpose was to analyse data available in the Registry and to integrate them with additional clinical and laboratory findings by filling up new e-forms in all cases with MDS and 5q- receiving LEN from October 31st, 2008 until the present. Diagnosis, treatment, follow-up and re-evaluation of patients were considered.

Study population included patients pre-treated and not pre-treated, with or without the integration form at the end of treatment. Pre-treated were defined as patients who were given LEN (from 1 to 12 cycles, median 3) before entering the AIFA registry. 158 patients (42 pre-treated and 116 not pre-treated) were eligible for this preliminary analysis. Median age was 75 (range, 38–89 years); 6 patients were younger than 50. There were 108 females (68.35%) and 50 males (31.6%) (table). Hematological findings evaluated at diagnosis were: hemoglobin (<8.5g/dL, 43% and >8.5g/dL, 57%), macrocytosis (MCV >98 fL, 54.4%), platelet count (<140×10⁹/L, 24.7%; between 140 and 400×10⁹/L, 56.3%; >400×10⁹/L, 19%). Median white blood cell count was 4× 10³/L with 54% neutrophils. Bone marrow blasts ≤5% were found in 75.9% of cases. The 5q- was detected by conventional cytogenetics in 131/158 cases (82.9%): it was isolated in 110 cases, associated with one additional in 15, and in complex karyotypes in 6. In 2 cases with normal karyotype and in 25 cases with failed cytogenetics the 5q- was demonstrated by fluorescence in situ hybridization (FISH). These cases could not be grouped as isolated or non-isolated. Patients received LEN at a daily dose of 10mg or 5 mg for 21 of 28 days as the starting dose. The dose and schedule was adjusted mainly based on blood count and hematological toxicity. Median time on treatment was 15.5 months (range, 1–45). Major and minor criteria for hematological and cytogenetic response are under evaluation. Transfusion independence at 6 months was reached in 77/103 cases (74.75%). Hematological toxicity could be evaluated in 148 cases. A total of 555 neutropenia events (36% grade 3 and 12.9% grade 4) and 422 thrombocytopenia events (10.9% grade 3 and 6.16% grade 4) were seen. Among 69 evaluable cases, 11 (15.9%) developed acute myeloid leukemia. In this group the median age was 72 (range, 62–85) and there were 4 males and 7 females. The median number of LEN cycles was 6 (range, 2–31). The median time from diagnosis of MDS was 34 months (range, 4–68). Chromosome 5q- at diagnosis was demonstrated by conventional cytogenetics in 8 cases (6 isolated and 2 with one additional change) and by FISH in 3.

The Italian Drug Agency (AIFA) Registry provided us with a large series of MDS cases with 5q- to investigate appropriatness of LEN prescription and management. As expected LEN was successful to obtain transfusion independence in this patient population. Hematological toxicity was manageable. The number of cases with leukemic evolution is in line with data reported in the literature. These cases will be further investigated.

Mecucci:CELGENE: Research Funding.