Optimizing lenalidomide therapy in renal impairment: analysis of renal response in the prospective REMNANT study in transplant-eligible newly diagnosed multiple myeloma

Renal impairment (RI) is a serious complication in multiple myeloma (MM), linked to poor survival and early mortality. Rapid renal recovery improves outcomes, yet patients with RI have been excluded from most key trials in transplant-eligible newly diagnosed (TE-ND) MM. REMNANT is an ongoing, academic, multicenter phase 2/3 study in TE-NDMM patients aged 18-75, regardless of baseline renal function. Here, we report a subanalysis of the non-randomized phase 2 component. All patients received four 21-day cycles of induction with bortezomib, lenalidomide, and dexamethasone. Lenalidomide was dosed higher than the recommended standard of care: 25 mg/day for eGFR ≥30 mL/min/1.73 m² and 15 mg/day for eGFR <30. Between August 2020 and September 2024, 382 patients were enrolled; 81 (21%) had RI, including seven (2%) on dialysis during cycle 1. Renal response was achieved in 77%, with complete renal response in 57%. Five dialysis-dependent patients became dialysis-independent. Overall response rates were similar, and adverse events were comparable between RI and non-RI groups, except for higher rates of anemia and thrombocytopenia in the RI cohort. Four RI patients (5%) experienced worsening renal function; two cases were possibly related to lenalidomide, both reversible. These findings support the safety and efficacy of increased lenalidomide-dosing during induction in TE-NDMM patients with RI, including those with severe impairment.