Quadruplet Regimen of Subcutaneous Daratumumab Plus Bortezomib, Thalidomide, and Dexamethasone Shows Efficacy for Newly Diagnosed MM
A weekly regimen of subcutaneous (SC) daratumumab in addition to bortezomib, thalidomide, and dexamethasone (D-VTd) therapy showed promising efficacy and manageable safety among patients with newly diagnosed (ND) multiple myeloma (MM) who are transplant-eligible, according to study results published in Annals of Hematology.
Previous research has found the quadruplet therapy of daratumumab plus bortezomib, thalidomide, and dexamethasone to be efficacious for the treatment of MM, however intravenous administration has been associated with increased infusion-related reactions. Researchers conducted a multicenter, observational study to determine the outcomes of the quadruplet regimen which included subcutaneous daratumumab for the treatment of newly diagnosed MM in a real-world setting.
Daratumumab was administered subcutaneously once weekly at 1,800 mg for 2 cycles followed by every 2 weeks for another 2 cycles, alongside bortezomib, thalidomide, and dexamethasone either orally, intravenously, or subcutaneously. Responses were assessed using International Myeloma Working Group (IMWG) criteria. The primary objective was evaluating the efficacy and safety of daratumumab plus bortezomib, thalidomide, and dexamethasone as a quadruplet induction and consolidation therapy for patients with R/R MM.
Overall, 51 patients who were treated with this quadruplet therapy were included. The median age was 58 years (range, 38 to 73). Autologous stem cell transplantation (ASCT) was reported by most patients (97.9%).
The median follow-up was 11.5 (range, 4.9 to 27.5) months and the median duration of treatment was 8.9 (1.0 to 15.7) months. The median range of induction cycles completed was 4.0 (range, 1.0 to 6.0). Patients who entered the consolidation phase (n = 37) had a median of 2 (range, 1.0 to 2.0) treatment cycles. Among 48 evaluable patients, the overall response rate (ORR) was 91.7%. Successful autologous stem cell transplantation was achieved by 43 of 44 patients.
In terms of safety, treatment-emergent adverse events of any grade occurred in 89.8% of patients with the most common being neutropenia (53.1%0, peripheral neuropathy (40.8%), febrile neutropenia (28.6%), and COVID-19 infection (22.4%). The most common grade 3 or 4 treatment-emergent adverse events were febrile neutropenia (18.4%) and neutropenia (16.3%). Serious adverse events occurred in 28.6% of patients which occurred more often in the induction phase than consolidation phase. Infections grade 3 or 4 were reported among 18.4% of patients, with the most common being COVID-19 (8.2%) and pneumonia (4.1%).
"In conclusion, daratumumab SC plus VTd demonstrated favorable responses and a safety profile that were comparable to those of its IV counterpart,” the researchers concluded.
“Overall, these findings gathered from a real-world clinical practice setting provide additional evidence to support the use of daratumumab SC plus VTd in transplant-eligible patients with ND MM,” they added.
Source:
Hungria V, Moura FL, Costa A, et al. Real-world data on the use of subcutaneous daratumumab plus bortezomib, thalidomide, and dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma. Annals of Hematology. Published online April 30, 2025. doi:10.1007/s00277-025-06365-3
