Carfilzomib, lenalidomide, and dexamethasone (KRd) is highly effective in patients with newly diagnosed multiple myeloma (MM) who are eligible for transplant, according to data published in Blood.
The phase 2 trial evaluated the efficacy of 4 cycles of KRd as induction therapy and 4 cycles as consolidation therapy, followed by 1 year of lenalidomide maintenance.
A total of 46 patients younger than age 66 years newly diagnosed disease who had no prior MM therapy were included and given induction therapy. There were 42 patients who underwent transplantation, and 40 patients who entered the maintenance phase.
Patients had rapid, deep responses that increased throughout the program.
A total of 26 of 42 patients (61.9%) achieved stringent complete response (sCR) after consolidation therapy. There were 27 of 42 patients (64.3%) who achieved at least CR, and 92.6% (n=25) of those patients had undetectable minimal residual disease (MRD) by flow cytometry. The median time to CR was 10.6 months.
After a follow-up of 60.5 months, 21 patients had disease progression, and 10 patients died.
There were 4 patients who had serious adverse events (AEs) that led them to discontinue combined treatment, and 11 patients discontinued at least 1 study drug because of AEs. A total of 31 patients reported 56 serious AEs, including cardiac disorders, vascular disorders, febrile neutropenia, and second primary neoplasm. Patients also reported infection and musculoskeletal disorders, along with other grade 3/4 treatment-emergent AEs.
The 5-year overall survival (OS) is estimated at 77.8% based on the trial results, and the median progression-free survival (PFS) was 56.4 months. Patients who were MRD-undetectable did not reach the median PFS, compared with patients who were MRD-persistent (PFS, 43.5 months).
The authors concluded that a combination regimen with KRd and 1 year of lenalidomide maintenance is effective for patients with newly diagnosed MM. The safety profile was acceptable, but cardiovascular and thrombotic toxicities should be closely monitored.
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Roussel M, Lauwers-Cances V, Wuilleme S, et al. Up-front carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRd final results. Blood. 2021;138(2):113-121. doi:10.1182/blood.2021010744