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

Abstract

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 serum free light chain (sFLC) reduction ≥50% within the first cycle, with a median time to sFLC reduction ≥50% of 3 days (95% confidence interval [CI], 3-7). Of 17 patients, 15 (88%) achieved sFLC reduction ≤500 mg/L after 1 cycle of treatment. The median time to sFLC reduction ≤500 mg/L was 14.5 days (95% CI, 9-49). The overall renal response at 3 months was 85% (n = 17), with complete, partial, and minor responses in 50% (n = 10), 10% (n = 2), and 25% (n = 5), respectively. Of the 9 patients who required dialysis at presentation, 4 of 7 (57.1%) and 6 of 7 (85.7%) were dialysis independent at 3 and 12 months, respectively. Hematologic overall response rate was 100%, with very good partial response (VGPR) in 90%. With a median follow-up of 25 months, progression-free survival was 46.5 months (95% CI, 11.9 to not reached), and the 2-year overall survival 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 sFLCs, improve renal outcomes, and provide an approach without plasmapheresis.

Graphical abstract

Figure 1.

Light chain kinetics outcomes in the first cycle of daratumumab-based therapy. (A) The median time to sFLC reduction ≥50% was 3 days (95% CI, 3-7). (B) The median time to sFLC reduction ≤500 mg/L was 14.5 days (95% CI, 9-49).

Figure 2.

Renal outcomes. (A) Renal response per IMWG criteria and the median time to sFLC ≤500 mg/L by subgroup. Eighty-five percent of patients had a renal response, with complete renal responses in 50%, partial renal response in 10%, and minor renal response in 25%. Complete renal response is defined as the best posttreatment creatinine clearance (CrCl) of at least 60 mL/min if the baseline eGFR was <50 mL/min per 1.73 m². Partial and minor renal responses to antimyeloma treatment are defined as best CrCl of 30 to 59 mL/min and 15 to 29 mL/min, respectively, if the baseline eGFR was <15 mL/min per 1.73 m². In addition, patients are determined to achieve a minor renal response if best CrCl response is between 30 and 59 mL/min and the baseline eGFR is from 15 to 29 mL/min per 1.73 m². (B) Dialysis outcomes in patients who started dialysis during inpatient hospitalization. Nine patients required dialysis during presentation. Two patients who started on dialysis died within 3 months (age 86 years, from aspiration pneumonia; age 87 years, from disease progression). Of the 7 patients, 4 (57.1%) came off dialysis by 3 months, and 6 (85.7%) were off dialysis at 1 year. ORR, overall response rate.