Lenalidomide-Induced Cytopenias In Patients with MDS Are Negatively Impacted by Reduced Glomerular Filtration Rate

The myelodsyplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders caused by dysplastic cellular proliferation accompanied by chronic peripheral cytopenias. Up to 90% of patients are found to be anemic upon presentation. Treatment with lenalidomide, a renally excreted drug, has been shown to abolish the need for red blood cell (RBC) transfusions in approximately two-thirds of MDS patients who harbor the deletion 5q abnormality. To date, there is no data regarding the degree of myelosuppression in patients with chronic kidney disease (CKD) who are receiving lenalidomide for the treatment of their MDS. Notably, increased myelosuppression related to abnormal glomerular filtration rate (GFR in mL/min) has been reported in myeloma patients on lenalidomide but has yet to be studied in patients with MDS (Niesvizky et al., 2007). We sought to evaluate the extent of cytopenias relative to GFR in patients who received lenalidomide for treatment of their MDS in the setting of the MDS 002/003 trials.

This is a retrospective chart review of patients with RBC transfusion dependent MDS treated with lenalidomide for symptomatic anemia in the setting of the 002/003 MDS trials at our center. All patients had an IPSS of low or intermediate risk-1 and were started on lenalidomide at 10mg daily. Patients were excluded from participation in the studies if their serum creatinine was > 2.5mg/dL. Blood counts prior to therapy and with each dosage change (defined as reduction, held dose or discontinuation) were recorded. Patients were stratified according to GFR <60 and GFR ≥60, with cytopenias related to lenalidomide identified in each group.

31 patients were identified. The median age was 70.5 years. 10 patients were male. 13 patients had normal karyotypes. 16 patients had del5q. 3 patients had other cytogenetic abnormalities. 17 patients were receiving ESAs prior to the study. 9 patients had a GFR of < 60 (including 2 with del5q), and 22 patients had a GFR ≥ 60 (including 13 with del5q). Of the 9 patients with a GFR < 60, 7 patients (78%) had their dose reduced/held for one or more grade 3/4 cytopenias: 5 with neutropenia, 2 with thrombocytopenia, and 1 with anemia. Of the 22 patients with a GFR ≥ 60, 17 (77%) required a dose change with 3 discontinuing lenalidomide. However, only 10 of these 22 patients (45%) required a dose change for one or more grade 3/4 cytopenias: 8 with neutropenia, 7 with thrombocytopenia, and 1 with anemia. Patients with a GFR <60 were maintained on lenalidomide for an average of 15 cycles (range 1 – 30). Patients with GFR ≥ 60 were maintained on lenalidomide for an average of 20 cycles (range 2 – 60 months).

The results of this study suggest that patients with CKD have a higher incidence of grade 3/4 myelosuppression when treated with lenalidomide. This effect appears to be greater than expected in those with non-del5q karyotypes and concurrent CKD. These observations require further investigation in a prospective manner. In the interim, consideration for initiating lenalidomide at a lower dose in patients with MDS and decreased renal function may reduce the incidence of myelosuppression, thereby potentially allowing for fewer dose modifications and longer treatment times. Our conclusion is in line with the recently published lenalidomide dose modification recommendations in patients with renal impairment and should prompt clinicians planning to treat MDS patients with lenalidomide to calculate GFR to determine an appropriate starting dose.

Gregory: Celgene: Research Funding. Venugopal: Celgene: Speakers Bureau. Shammo: Celgene: Honoraria, Research Funding, Speakers Bureau.