Abstract Introduction: Carfilzomib (K) and daratumumab (D) combination has earning FDA approval for relapsed/refractory multiple myeloma. The MASTER trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) therapy show significant clinical efficacy and favorable safety profile in newly diagnosed Multiple Myeloma (NDMM). Building upon these findings, this retrospective analysis evaluates the real-world effectivity and tolerability of DK-based combination therapy in patients with NDMM not undergoing autologous stem cell transplantation (ASCT) Methods: This single-center retrospective cohort study was conducted at The First Affiliated Hospital of Kunming Medical University. Eligible participants included adults (age ≥18 years) with NDMM deemed ineligible for ASCT or opting against transplant-based therapy and exhibited an Eastern Cooperative Oncology Group (ECOG) performance status of 0–3. Patients (n=21) were enrolled between May 11, 2023, and July 15, 2025. The DK-based regimens (DKd; DKBd; DKCd; DKRd) — combining daratumumab, carfilzomib, dexamethasone ± bendamustine, cyclophosphamide, or lenalidomide — were administered in 28-day cycles (≥2 cycles). The primary efficacy endpoint was the overall response rate (ORR). Secondary endpoints included rates of very good partial response (VGPR) or better and complete response (CR), progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). Results: The cohort comprised 21 patients (median age: 62 years range: 49–79; 42.9% aged ≥65 years; male: 66.7%). Patient baseline characteristics included ISS Stage III disease (42.9%), extramedullary involvement (19.0%), elevated lactate dehydrogenase (14.3%), and anemia (33.3%) and patients received a median of 3 treatment cycles (range: 2–6). Regimens included DKd (n=13, 61.9%), DKBd (n=2, 9.5%), DKCd (n=2, 9.5%), and DKRd (n=4, 19.0%). The overall response rate (ORR) for DK-based regimens was 90.5% (19/21), comprising CR (n=10, 47.6%), VGPR (n=7, 33.3%), and PR (n=2, 9.5%). In the DKd subgroup (n=13), ORR reached 92.3% (CR: 46.2%, VGPR: 38.5%, PR: 7.7%). Patients completing ≥4 treatment cycles (n=8) demonstrated a trend toward higher ≥VGPR rates compared to those receiving 4 cycles (n=13) (100% vs. 69.2%, P=0.13), though CR rates remained comparable (50.0% vs. 46.2%). Notably, 75% (3/4) of patients with extramedullary disease achieved responses (CR: n=1, VGPR: n=1, PR: n=1). With a median follow-up of 12.3 months (data cutoff: July 15, 2025), median PFS and median OS were not reached. The 12-month PFS rate was 87% (95% CI: 72–100%). TRAEs were hematologic toxicities predominated (23.8%), with grade ≥3 anemia (19.0%) and neutropenia (4.8%). Notable non-hematologic events included hypertension (14.3%, grade 3: 2 cases) and grade 3 heart failure in a patient with pre-existing cardiomyopathy. The cardiac event emerged during cycle 2 of DKRd therapy, presenting as acute dyspnea with bilateral rales and elevated B-type natriuretic peptide(BNP) 5000 pg/mL. Carfilzomib dose reduction achieved cardiac stabilization, enabling treatment continuation through cycle 8 (August 2024) with maintained hematologic response. No treatment-related mortality was observed. Conclusion: DK-based regimens achieved high effectivity in patients with NDMM not undergoing ASCT, including those with EMD. Efficacy improved with prolonged treatment. The combination of carfilzomib and daratuzumab aligns with published data, confirming feasibility and effectiveness. No severe AEs were observed in elderly patients (≥65 years). This regimen represents a safe and effective option for NDMM patients not undergoing ASCT, even in cases with limited baseline conditions.
Xu et al. (Mon,) studied this question.