Al-Ola A Abdallah, Associate Professor and Plasma Cell Disorder Program Director of the Division of HMCT at the University of Kansas Medical Center, shared a post on X:
“Abstract 8/10: ASH25
New data alert in Multiple Myeloma!
Interim results from the Phase III COBRA trial compare KRd (carfilzomib/lenalidomide/dex) versus VRd (bortezomib/lenalidomide/dex) in newly diagnosed MM (NDMM).
Why it matters: VRd is the current frontline standard. KRd has shown strong activity, but previous head-to-heads (e.g., ENDURANCE) didn’t show PFS benefit. COBRA revisits this across all NDMM patients, regardless of transplant eligibility or cytogenetics.
Study design: 250 patients randomized 1:1 to KRd versus VRd.Co-primary endpoints:
- MRD-negative CR at 12 months
- Progression-free survival (PFS) Both were met at interim analysis.
MRD results: At 10⁻⁵ sensitivity:
- KRd: 31%
- VRd: 18%
At 10⁻⁶ sensitivity:
- KRd: 19%
- VRd: 7% KRd significantly improves depth of response.
Progression-free survival: KRd significantly prolonged PFS versus VRd.
- Median PFS: Not reached (KRd) versus 49 months (VRd)
- HR = 0.57 (p = 0.0095) A notable PFS advantage not seen in ENDURANCE.
Other efficacy findings:
- ORR high in both arms: 94% KRd versus 91% VRd
- CR or better: 71% KRd versus 53% VRd
Clear improvement in depth of response with KRd.
Safety:
- Grade ≥3 AEs: 72% KRd versus 62% VRd
- Neutropenia ≥3: 21% KRd versus 11% VRd
- Peripheral neuropathy (any grade): 17% KRd versus 56% VRd
- Cardiac events (any grade): 18% KRd versus 10% VRd
Two KRd treatment-related deaths reported.
Takeaway: COBRA demonstrates superior efficacy of KRd over VRd in frontline NDMM, including MRD-negativity and PFS—with expected, manageable toxicity profiles. Supports further evaluation of KRd-based induction strategies.
Abstract Number: abs25-10191.”
Title: 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.
Authors: Dominik Dytfeld, Tadeusz Kubicki, Agata Tyczynska, Marcin Rymko, Krzysztof Jamroziak, Fredrik Schjesvold, Jaroslaw Piszcz, Tomasz Wrobel, Krzysztof Giannopoulos, Bartosz Pula, Agnieszka Konska, Pawel Steckiewicz, Juha Lievonen, Mateusz Ziarkiewicz, Pawel Bernatowicz, Lidia Gil, Anna Lojko-Dankowska, Magdalena Matuszak, Jan Zaucha, Maria Czyzewska, Kamil Wisniewski, Magdalena Olszewska-Szopa, Anna Pula, Frank Wen, Frida Bugge Askeland, Valdas Peceliunas, Jennifer Cooperrider, Ken Jiang, Theodore Karrison, Benjamin Derman, Andrzej Jakubowiak
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