Conference Coverage

Carfilzomib-Based KRd Regimen Demonstrates Superior Efficacy to VRd in Newly Diagnosed Patients with Multiple Myeloma

Edited by:
Anthony Calabro, MA

Key Highlights

  • Carfilzomib, lenalidomide, and dexamethasone (KRd) significantly improved minimal residual disease (MRD)–negative complete response rates compared with bortezomib, lenalidomide, and dexamethasone (VRd) at both 10⁻⁵ and 10⁻⁶ thresholds.
  • Progression-free survival was significantly longer with KRd, meeting the co-primary endpoint.
  • Rates of grade ≥3 adverse events were higher with KRd, including increased neutropenia and cardiac events.
  • Both regimens achieved high overall response rates, though KRd produced deeper responses.

Interim results from the phase III COBRA trial indicate that carfilzomib, lenalidomide, and dexamethasone (KRd) provides superior efficacy compared with bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma. Researchers presented their study results at the 67th ASH Annual Meeting and Exposition in Orlando, FL.

The trial assessed whether KRd could improve minimal residual disease (MRD)–negative complete response and progression-free survival, the 2 co-primary endpoints, in a frontline setting. Prior studies, including the ENDURANCE trial, showed similar progression-free survival between the regimens, underscoring the clinical relevance of this updated evidence.

Researchers randomized 250 patients with NDMM 1:1 to receive KRd (n = 126) or VRd (n = 124), regardless of transplant eligibility or cytogenetic risk. Treatment duration totaled 24 cycles, followed by lenalidomide 15 mg daily until progression or intolerance. MRD was centrally assessed using next-generation sequencing. The primary analysis occurred once all patients could complete the 12-month MRD evaluation. At the time of interim analysis, 86 of 106 planned progression-free survival events (81%) had occurred.

Study Findings

After a median follow-up of 35 months, both co-primary endpoints were met. KRd produced higher MRD-negative complete response rates at the 10⁻⁵ threshold (31% vs 18%; OR = 2.08; P = .016) and the 10⁻⁶ threshold (19% vs 7%; OR = 3.01; P = .008). Progression-free survival (PFS) favored KRd, with median PFS not reached versus 49 months with VRd (HR = 0.57; P = .0095).

Overall response rates were similar (94% KRd vs 91% VRd); however, KRd yielded more complete responses or better (71% vs 53%; OR = 2.11; P = 0.005). At data cutoff, 20 patients in the KRd arm and 18 in the VRd arm had died.

Grade ≥3 adverse events occurred in 72% of KRd recipients and 62% of VRd recipients. Neutropenia was the most frequent severe hematologic toxicity (21% vs 11%). Peripheral neuropathy of any grade occurred in 17% of KRd patients compared with 56% receiving VRd. Cardiac events of any grade were more frequent with KRd (18% vs 10%). Two treatment-related deaths occurred in the KRd arm due to pneumonia and COVID-19.

Clinical Implications

According to the study authors, these interim data suggest that KRd leads to deeper responses and improved progression-free survival compared with VRd in NDMM while maintaining a safety profile consistent with known toxicities. The findings indicate potential value for KRd as an induction regimen across risk groups, regardless of autologous transplant eligibility.

Expert Commentary

“The randomized phase III COBRA trial showed superior efficacy of KRd compared with VRd in NDMM, with safety profile consistent with prior reports,” the researchers concluded. “These findings support further evaluation of KRd-based induction regimens in NDMM.”

Reference
Dytfeld D, Kubicki T, Tyczynska A, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) versus bortezomib, lenalidomide and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM): interim results from the randomized Phase III COBRA trial. 67th ASH Annual Meeting and Exposition; December 6-9; Orlando, FL. Accessed December 5, 2025. https://submit.hematology.org/program/presentation/679275.