Study Highlights Importance of Early Daratumumab-Based Therapy for Patients With MM and Acute Kidney Injury

Early initiation of daratumumab-based combination therapy rapidly reduces serum free light chains (sFLCs), restores renal function, and improves survival in patients with newly diagnosed multiple myeloma (MM) admitted with acute kidney injury (AKI), according to a study published in Blood Advances.

“Acute kidney injury from myeloma is one of those situations where it’s important to start therapy urgently, with the hope of restoring kidney injury, avoiding the need for dialysis, or helping patents come off dialysis sooner,” Andrew Yee, MD, senior author of the study and clinical director of the Center for Multiple Myeloma at Massachusetts General Hospital Cancer Center, told Blood Cancers Today.

The retrospective, single-center study evaluated 20 patients with a new diagnosis of MM and AKI who received daratumumab during or after inpatient admission at Massachusetts General Hospital between December 2018 and December 2023. Patients had a median creatinine level of 6.5 mg/dL at admission, and 9 patients required dialysis during hospitalization.

All 20 patients received daratumumab combination therapy, including daratumumab, bortezomib, cyclophosphamide, and dexamethasone (dara-VCd) for 11 patients (55%) and daratumumab, bortezomib and dexamethasone (dara-Vd) for 9 patients (45%).

Light Chain Kinetics

Within the first cycle of daratumumab-based therapy, all patients achieved sFLC reduction of 50% or more in a median of 3 days. Fifteen of 17 patients (88%) achieved sFLC reduction of 500 mg/L or less after the first cycle in a median of 14.5 days. One patient did not have an sFLC measurement by 28 days, 1 patient died, and 1 patient was lost to follow-up.

“Historically, plasmapheresis has been considered to reduce the light chain burden— although there is significant heterogeneity in practice —and recent studies with high cutoff dialyzers have raised the question of the value of the mechanical removal of light chains,” said Dr. Yee. “As myeloma therapies become better over time, we can achieve rapid light chain reduction with myeloma therapy alone.”

Renal and MM Response

Renal and MM disease responses were assessed by International Myeloma Working Group (IMWG) criteria. At 3 months, 17 patients (85%) achieved an overall renal response. Ten (50%) patients achieved a complete response, 2 (10%) achieved a partial response, and 5 (25%) achieved a minor response. Compared with patients who had less than a complete response, those who had a complete renal response showed a trend toward faster time to sFLC of 500 mg/L or less (median 22.5 days vs 10 days, respectively; P=0.2).

Of those who required dialysis, 4 of 7  patients (57.1%) were dialysis independent at 3 months, and 6 of 7 patients (85.7%) were dialysis independent at 12 months. Two patients undergoing dialysis died within 3 months (cause was aspiration pneumonia in 1 and disease progression in the other), and 1 patient continued dialysis at 12 months.

As for MM response, all patients achieved a hematologic overall response, with 90% achieving a very good partial response and 10% achieving a partial response. At a median follow-up of 25 months, progression-free survival was 46.5 months, and 2-year overall survival was 83.7%.

“It’s important to start effective therapy early in this challenging patient population, and daratumumab can be a key component of that effective therapy. These results can be achieved without plasmapheresis,” Dr. Yee explained. “From a practical standpoint, there can be reimbursement concerns with using daratumumab as an inpatient, and hopefully this study provides further support to starting daratumumab early, even as an inpatient.”

Reference

Kim EB, Malespini JE, Lei M, et al. Early daratumumab therapy improves renal outcomes in newly diagnosed myeloma patients admitted with kidney injury. Blood Adv. Published online March 14, 2025. doi:10.1182/bloodadvances.2025015901