Reduced Dose Lenalidomide Is Safe and Effective in Deletion (5q) MDS Patients with Severe Renal Impairment: Report of Two Cases.

Introduction: Lenalidomide (Len) is highly active in the treatment of MDS with deletion 5q (del[5q]) (List et al. NEJM 2006). Patients with renal impairment have often been excluded from Len studies because of potential for delayed excretion with increased risk for adverse events. We present 2 MDS patients with 5q− syndrome and renal impairment who were treated with Len at reduced dosage.

Patient 1: A 50-year-old woman presented with shortness of breath on exertion, pallor, and tachycardia. Laboratory tests showed hemoglobin (Hb) 3.9 g/dL with significant macrocytosis; white blood cell count (WBC) of 3.2 × 10⁹/L; and creatinine 2.66 mg/dL (normal value, < 1.1 mg/dL). Bone marrow aspirate was consistent with World Health Organization 5q− syndrome. Abdominal ultrasound revealed unilateral renal agenesis. The patient required 2 packed red blood cell (RBC) units every 2 to 3 weeks. Glomerular filtration rate (GFR) was severely impaired (23 mL/min). Len was initiated at 5 mg/d and increased to 10 mg/d after 4 weeks. The patient showed a fast and sustained hematologic response, Hb of 10–11 g/dL without exogenous erythropoietin, and achieved transfusion independence within 6 weeks. Due to decreased WBC of 1.3 × 10⁹/L, and a platelet count (plt) of 57 × 10⁹/L, indicating thrombocytopenia, Len was adjusted to a daily alternating dose of 5 mg and 10 mg, respectively. Complete cytogenetic remission was achieved by 6 months of treatment.

Patient 2: An 83-year-old female presented with sustained anemia despite treatment with recombinant erythropoietin. Bone marrow findings and peripheral blood features were consistent with the 5q− syndrome. The patient was transfusion dependent and received a single treatment cycle with azacitidine, but developed acute renal insufficiency, accompanied by an elevation in creatinine to 4.8 mg/dL. She continued supportive care measures receiving 2 units of RBC every 4 weeks. Len was initiated at 5 mg daily. GFR at start of therapy was moderately decreased (31 mL/min). After 6 weeks of treatment the patient developed a generalized rash, occupying 30–50% of the body, which subsided with temporary therapy cessation. Laboratory studies at 6 weeks revealed a WBC of 1.58 × 10⁹/L, with an absolute neutrophil count (ANC) of 3.5 × 10⁹/L, Hb of 12.3 g/dL and plt of 42 × 10⁹/L. Because of progressive decline in the patient’s Hb levels Len was resumed 5 months later at a dose of 5 mg 3 times per week. This was well tolerated. Complete cytogenetic remission was achieved after 10 months of follow-up.

Conclusions: These cases show that Len can be administered safely to MDS patients with renal insufficiency and with preserved clinical activity. In addition, the present observations suggest that Len therapy could abrogate the need for use of additional erythropoietin in these patients.