Impact of Baseline Renal Function on Transfusion-Independence Response, Survival, and Transformation to Acute Myeloid Leukemia in Patients with Deletion 5q: A Sub-Analysis of the MDS-003 Study

Introduction: Lenalidomide reduced transfusion requirements and reversed cytologic and cytogenetic abnormalities in patients who have myelodysplastic syndrome (MDS) with the chromosome 5q31 deletion del(5q)] (List et al., NEJM 2006). Dose-adjusted lenalidomide is safe and effective in MDS patients with del(5q) and severe renal impairment (Knop et al., Leuk Lymph 2008), but the impact of baseline renal function on outcomes has not been specifically studied. This MDS-003 clinical trial sub-analysis investigates the impact of baseline renal function on the transfusion-independence (TI) response, overall survival, and transformation to acute myeloid leukemia (AML).

Methods: Transfusion-dependent, Low/Int-1-risk patients with primary MDS and del(5q) with/without additional cytogenetic abnormalities were treated with lenalidomide 10 mg daily for 21 days every 28 days. Patients were treated until disease progression, treatment failure, or treatment-limiting adverse events. This sub-analysis included patients with normal renal function (creatinine clearance [CrCl] >80 mL/min) and patients with mild (CrCl 50–80 mL/min), moderate (30–50 mL/min), or severe renal impairment (CrCl <30 mL/min). CrCl was calculated according to the Cockcroft-Gault formula. Red blood cell (RBC) transfusion-dependent anemia was defined as having received ≥2 units of RBCs within 8 weeks of the first day of study treatment. Neutropenia was defined as a baseline absolute neutrophil count of <1,000/μL. Thrombocytopenia was defined as a baseline platelet count of < 100,000/μL. TI response, overall survival, and transformation to AML were assessed.

Results: Of 148 patients enrolled in the study, 70 patients had normal renal function and 70 patients had renal impairment (47 mild, 19 moderate and 4 severe impairment; with renal data missing for 8 patients). The TI response was 44/70 (63%) for patients with normal renal function and 48/70 (69%) for patients with impaired renal function (P=0.47). In the subcategories, the TI responses were 79%, 53% and 25% for mild, moderate and severe impairment, respectively (P=0.07, P=0.42 and P=0.13 vs. normal function). Renal impairment resulted in shorter median overall survival compared with no renal impairment (hazard ratio of 2.88, 95% confidence interval, 2.24–3.45). The transformation to AML rate was 19% for normal patients and 20% for patients with renal impairment.

Conclusion: In this analysis, baseline renal function does not have a significant impact on achieving transfusion independence or transformation to AML. Patients with moderate to severe renal impairment had a shorter survival than patients with normal renal function.