Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)
Category: Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)
Dara-VCd in Newly Diagnosed Multiple Myeloma with Severe Renal Impairment: A Prospective Multicenter Single-Arm Study
Yang Yang, MD, PhD
Associate Chief Physician
The First Affiliated Hospital, Zhejiang University School of Medicine
Renal impairment (RI) is one of the most common complications of multiple myeloma (MM). The combination of bortezomib, cyclophosphamide, and dexamethasone (VCd) has significantly improved treatment outcomes and overall survival (OS) in MM patients. However, persistent RI after treatment remains a poor prognostic factor. Recent studies have demonstrated that Daratumumab not only deepens hematologic responses but also promotes renal recovery. Nevertheless, patients with severe RI are frequently excluded from clinical trials. Therefore, we conducted a prospective study to evaluate the efficacy and safety of the DVCd regimen (daratumumab + VCd) in newly diagnosed MM (NDMM) patients with severe RI.
Methods:
This is an ongoing prospective multicenter single-arm study. NDMM patients with myeloma-related RI (eGFR< =40 ml/min/1.73m2) were enrolled. Patients received one initial cycle of VCd (1.3 mg/m2 bortezomib at day 1,4,8,11 of 28-day cycle, Cyclophosphamide 200mg/m2 at day 1,4,8,11, and dexamethasone 20mg on the day of and after bortezomib). Thereafter Daratumumab was added to VCd regimen (16mg/kg weekly for 2 cycles, bi-weekly for next 4 cycles, monthly up to 24 does, and subsequently every 8 weeks until disease progression or unacceptable toxicity). Autologous stem cell transplantation (ASCT) was administered to transplant-eligible patients following induction therapy. During the maintenance phase, a Daratumumab-based doublet regimen (daratumumab with bortezomib) was recommended. The primary endpoint was the renal overall response rate (ORR) after 4 cycles of induction therapy. Secondary endpoints included hematological ORR, progression-free survival (PFS), and OS.
Results:
A total of 51 patients were enrolled across five centers between September 25, 2023, and March 31, 2025. Three patients discontinued after one cycle and were lost to follow-up. At data cutoff, 43 had completed four induction cycles, and five remained on treatment. The median age was 63 years (range, 47–79), and 25.0% (n=12) required dialysis at baseline. High-risk cytogenetics (del[1p32], del[17p], t[4;14], or +1q21) were present in 58.3% (n=28). Based on R2-ISS, 27.1% and 37.5% of patients were stage III and IV, respectively. Forty-three patients were evaluable for efficacy. Median follow-up was 10.8 months (range, 5.1–18.2). Five (11.6%) underwent ASCT after induction. Renal ORR was 76.7%, including 18.6% CR, 20.9% PR, and 37.2% MR. Hematologic ORR was 95.1%, comprising 26.8% ≥CR, 51.2% VGPR, and 17.0% PR. The most common grade 3/4 adverse events were neutropenia (18.6%) and infections (20.9%). Two patients progressed during follow-up, including one with double-hit cytogenetics who died. Median PFS and OS were not reached; estimated 12-month PFS and OS were both 95.2%.
Conclusions:
DVCd combination regimen could deepen both renal and hematologic responses in NDMM patients with severe RI.