Efficacy and Safety of Daratumumab Combined with Bortezomib and Dexamethasone Regimen in Newly-Diagnosed Multiple Myeloma Patients

Background: Multiple myeloma (MM) is an incurable clonal plasma cell dysplasia, the second most hematological malignancy. Renal insufficiency (RI) is a common complication of MM and is associated with poor prognosis and shorter survival. Treatment options for patients with RI are limited and can lead to higher drug-related adverse events. Several authoritative guidelines recommend a triplet-drug combination regimen based on bortezomib and dexamethasone (Vd) for MM patients with RI. The NCCN guidelines suggest regimens containing bortezomib and/or daratumumab. Daratumumab (Dara) targets myeloma cells via immune-mediated mechanisms and is primarily metabolized through internalization, with minimal renal excretion. Previous clinical trials of Dara-containing regimens in patients have shown good hematologic response depth and speed, high renal response rates, and reduced risk of disease progression and mortality. However, there are no clinical data available on the use of the daratumumab combined with bortezomib and dexamethasone (DVd) regimen in newly diagnosed multiple myeloma (NDMM) patients. Therefore, this study aims to evaluate the efficacy and safety of the DVd regimen in NDMM.

Methods:

Eligible NDMM were enrolled in this prospective clinical study (China National Medical Research Registration and Filing Information System Number: MR-21-23-018124). In the first treatment cycle, patients received the Vd regimen, followed by the DVd weekly regimen from the second to the fifth cycle. Each treatment cycle lasted 28 days, with 5 cycles observed in total. Efficacy and safety assessments were conducted after each cycle. The primary endpoints were overall response rate (ORR) and renal response rate (RRR); secondary endpoints included minimal residual disease (MRD) negativity rate and safety events.

Result:

1. A total of 44 NDMM patients were included in this study, including 22 patients with RI and another 22 without RI. All patients achieved an ORR of 100% after 1 cycle of Vd regimen and 4 cycles of DVd regimen. Among patients with RI, 18.2% achieved MRD negativity, 9.1% achieved complete response (CR) or stringent complete response (sCR), and 31.8% achieved very good partial response (VGPR). In patients without RI, 22.7% achieved MRD negativity, 22.7% achieved CR or sCR, and 13.6% achieved VGPR. The proportion of patients achieving ≥VGPR was consistent between the two groups.

2. The RRR in patients with RI was 90.91%, with 63.64% achieving complete response, 13.64% partial response, and 13.64% minor response (3 patients). Only 9.09% (2 patients) showed no response in renal function. Only 1 patient required hemodialysis due to severe heart failure, while the rest were weaned off dialysis.

3. Among 22 NDMM patients with RI, 13 patients had an iFLC > 50% reduction after the first DVd therapy, and 15 patients showed a > 90% reduction in iFLC after 4 cycles of the DVd regimen.

4. In different eGFR groups, 100% complete renal response was observed in patients with eGFR between 30-59 ml/(min×1.73m²), 60% partial response or better in patients with eGFR between 15-29, and 56% partial response or better in patients with eGFR below 15. No significant differences in hematologic efficacy were observed among the different eGFR groups.

5. The DVd regimen was well-tolerated, with only 3 patients experiencing 3-grade lymphopenia and anemia; other hematologic adverse events were grade 1-2 and could be corrected with symptomatic supportive treatment. Non-hematologic adverse events mainly included fever and fatigue, with only 1 patient experiencing infectious fever during Dara treatment, which was resolved with symptomatic anti-infective therapy.

Conclusion:

The addition of daratumumab to Vd significantly increase the remission rate, deepen the depth of remission, and improve the poor prognosis in NDMM patients with renal impairment. It also rapidly reduces involved light chain levels and promotes renal function recovery. The DVd regimen is well-tolerated, without introducing new safety issues.

Key words: Daratumumab; Multiple Myeloma; Renal Impairment

No relevant conflicts of interest to declare.