Superior 12-month progression-free survival with frontline DVd versus VRd in patients with newly diagnosed multiple...

Multiple myeloma, a malignant plasma cell disorder, has undergone remarkable therapeutic advancement. The lenalidomide-bortezomib-dexamethasone (VRd) regimen has been firmly established as one of the standard induction therapies for newly diagnosed multiple myeloma (NDMM) patients, owing to its substantial clinical benefits. Despite its superiority in achieving good responses, VRd harbors intrinsic limitations in high relapse risk, and treatment-related toxicities. Dara (Daratumumab)-containing regimens are prioritized as frontline treatment options per international guidelines. While the quadruplet Dara-VRd combination further improves clinical efficacy, it carries notable safety and tolerability burdens and is suboptimal for vulnerable patient subgroups: it is poorly tolerated by elderly or frail individuals, requires complicated dose modifications for patients with renal impairment, and impairs hematopoietic stem cell mobilization in transplant-eligible candidates. The triplet daratumumab-bortezomib-dexamethasone (DVd) regimen has yielded encouraging anti-tumor activity in patients with relapsed/refractory multiple myeloma (RRMM), which motivated us to explore its clinical performance in the frontline setting. The present study aimed to compare the efficacy and safety of frontline DVd versus VRd induction, to generate real-world clinical evidence guiding individualized treatment decision-making for NDMM.

To compare the efficacy, safety and real-world applicability of DVd versus VRd in NDMM patients.

This multicenter prospective study enrolled 206 NDMM patients (DVd: n = 98; VRd: n = 108) from 12 Chinese centers (March 2023-March 2025). Propensity score matching (PSM; covariates: age, serum creatinine, Durie-Salmon stage, ISS stage) generated a balanced cohort (70 patients/group). Key endpoints: overall response rate (ORR), renal response rate (RRR), time to renal recovery (TTRR), progression-free survival (PFS), duration of response (DOR), and adverse events (AEs; NCI CTCAE v5.0).

Both groups had high completion rates after induction (95.9% [94/98] vs. 94.4% [102/108], p = 0.623). ORR was comparable in the original cohort (DVd 97.9% vs. VRd 94.1%, p = 0.282), but DVd achieved faster response (median time to response: 1.85 vs. 2.27 months, p = 0.002), despite worse baseline characteristics. In the propensity score-matched cohort, the two groups also had similar ORR (DVd 97.1% vs. VRd 97.0%, p = 1.00) with comparable deep remission rates (MRD negativity: 4.3% vs. 7.3%; sCR/CR: 30.4% vs. 32.3%). Renal response: Despite lower mean baseline eGFR in DVd group (23.7 vs. 32.7 mL/min, p < 0.001), magnitude of eGFR improvement was comparable (ΔeGFR: 15.2 vs. 12.7 mL/min, p = 0.48) in the original cohort. In the propensity score-matched cohort, 78.6% (22/28) in DVd and 95.0% (19/20) in VRd achieved response (renal-CR: 50.0% vs. 70.0%; renal-PR: 7.1% vs. 15.0%; renal-MR: 21.4% vs. 10.0%, p = 0.207). PFS: In the original cohort, the 12-month PFS rate was 92.8% in the DVd group and 79% in the VRd group. In the propensity score-matched cohort, the 12-month PFS rate in DVd and VRd group was 91.9% vs. 84%. Subgroup analyses confirmed PFS benefits in patients with high-risk genetics, ISS stage III, and transplant-eligible patients. DOR: In the original cohort, the 12-month DOR rate was 92.5% in the DVd group and 74.6% in the VRd group. In the propensity score-matched cohort cohort, the 12-month DOR rate in DVd and VRd group was 91.9% vs. 84%. Subgroup analyses confirmed DOR benefits in patients with high cytogenetic risk, ISS stage III, and transplant-eligible patients.

Across both the original and PSM cohorts, the DVd regimen had relatively fewer severe adverse reactions than the VRd regimen with no statistical significance. After PSM, the patients in DVd group vs. VRd group: grade 3-4 neutropenia (5.71% vs. 10%, p = 0.346) and thrombocytopenia (10% vs. 14.29%, p = 0.438), grade 3-4 ALT elevation (7.14% vs. 10%, p = 0.546).

DVd demonstrates faster response, superior PFS and DOR, accompanying with relatively less toxicity in NDMM patients. These real-world data support DVd as a frontline option for NDMM patients.