Treatment of newly-diagnosed multiple myeloma (MM) with a transplant-free regimen of carfilzomib plus cyclophosphamide and dexamethasone (KCd) with carfilzomib maintenance was inferior to autologous hematopoietic stem cell transplant (HSCT), according to the results of the phase 2 CARDAMON study published in Lancet Haematology.
Given that HSCT is associated with morbidity and some mortality, the authors evaluated whether treatment with a carfilzomib-based regimen and maintenance therapy without HSCT was noninferior.
The open-label, phase 2 CARDAMON randomly assigned 218 patients with newly-diagnosed MM to receive KCd consolidation or undergo high-dose melphalan consolidation followed by autologous HSCT. All patients received KCd induction and carfilzomib maintenance therapy. The primary endpoint was at least very good partial response (VGPR) and progression-free survival (PFS) at 2 years. The median follow-up was 40.2 months.
There were 57.7% of patients who achieved at least a VGPR after induction, including 3% who achieved a complete response and 5% a stringent complete response. After consolidation, 78.0% and 77.1% of patients achieved at least a VGPR with KCd or HSCT, respectively.
Noninferiority of PFS was not met, with a rate of 68% with KCd and 75% with HSCT at 2 years (hazard ratio, 1.35; 70% CI, 1.11-1.64; P =.11). The 2-year overall survival (OS) was 90.8% in the KCd group compared with 94.4% in the HSCT group. The median OS was not reached.
Grade 3-4 adverse events occurred among 66% of patients during induction, and 5 patients died. Among patients in the KCd group, grade 3-4 AEs occurred among 45% and 45% of patients during consolidation and maintenance, respectively. Among patients in the HSCT group, grade 3-4 AEs occurred among 65% of patients and there was 1 death.
The authors concluded that “KCd did not meet the criteria for noninferiority compared with autologous HSCT.”
Disclosures: This study was supported in part by Amgen. Please see the original reference for a full list of disclosures.
Yong K, Wilson W, de Tute RM, et al. Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib–cyclophosphamide–dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial. Lancet Haematol. Published online December 15, 2022. doi: 10.1016/S2352-3026(22)00350-7