Exclusion of patients with renal impairment from phase 3 randomized controlled trials in hematologic malignancies

Phase 3 randomized controlled trials (RCTs) are key for assessing the efficacy and safety of new drugs used in hematologic malignancies. Up to 50% of patients with hematologic malignancies have renal impairment. The objective of this study was to perform a comprehensive analysis of the exclusion of patients with renal impairment from phase 3 RCTs of drugs administered systemically in leukemias, lymphomas, and multiple myeloma. Our analysis included 554 RCTs registered with ClinicalTrials.gov and started between 2009 and 2023. Overall, 370 (66.8%) RCTs had an exclusion criterion related to renal impairment. The most common criteria involved creatinine clearance/estimated glomerular filtration rate (GFR; n = 222; 40.1%) followed by serum creatinine level (n = 166; 30%). In multivariable analysis, the odds of the renal exclusion criteria were significantly higher in leukemia trials (adjusted odds ratio (OR), 1.62; 95% confidence interval (CI), 1.06-2.49; p = .03) and RCTs funded by commercial sponsors (adjusted OR, 1.66; 95% CI, 1.11-2.49; p = .01). Trials of chemotherapy were significantly associated with the odds of the renal exclusion criteria in univariate analysis (OR, 1.69; 95% CI, 1.18-2.41; p = .004), but not in multivariable analysis (adjusted OR 1.3; 95% CI 0.89-1.89; p = .18). While the nephrotoxic effects of anticancer drugs may occur more often in individuals with pre-existing renal decline, careful relaxation of the eligibility criteria in some trials should be considered to enable the investigators to assess the benefits and harms of the investigational drugs in the growing population of patients with a hematologic malignancy accompanied by renal impairment.