Early daratumumab therapy improves renal outcomes in newly diagnosed myeloma patients admitted with kidney injury

• Early use of daratumumab combinations in multiple myeloma admitted with kidney injury rapidly reduces serum free light chains.

• Early initiation of daratumumab combinations improves renal function and provides an approach that avoids plasmapheresis.

Cast nephropathy is the most common cause of acute kidney injury (AKI) in patients with multiple myeloma (MM). A prompt reversal of renal injury is paramount for improving clinical outcomes. Daratumumab, an anti-CD38 monoclonal antibody, has significant clinical efficacy in MM. We describe the effects of daratumumab-based therapy in 20 patients admitted with a new diagnosis of MM and AKI with a median creatinine of 6.5 mg/dL. All patients (100%) achieved sFLC reduction ≥50% within the first cycle with median time to sFLC reduction ≥50% of 3 days (95% CI 3-7). Fifteen of 17 patients (88%) achieved sFLC reduction ≤500 mg/L after 1 cycle of treatment. Median time to sFLC reduction ≤500 mg/L was 14.5 days (95% CI 9-49). Overall renal response at 3 months was 85% (n=17), with complete, partial, minor responses in 50% (n=10), 10% (n=2), and 25% (n=5), respectively. Out of the 9 patients who required dialysis at presentation, 4 out of 7 (57.1%) and 6 out of 7 (85.7%) were dialysis independent at 3 and 12 months, respectively. Hematologic ORR was 100% with VGPR in 90%. With median follow-up of 25 months, PFS was 46.5 months (95% CI, 11.9-NR) and 2-year OS was 83.7% (95% CI 68.4-100%). These findings highlight the importance of early initiation of daratumumab-based treatment in patients with MM and AKI to induce rapid and significant reductions in sFLC, improve renal outcomes, and provide an approach without plasmapheresis.