Carfilzomib-Lenalidomide-Dexamethasone Regimen Compared With Bortezomib and HSCT Treatment for Patients With Multiple Myeloma

Results from the Randomized Phase 2 CARDAMON Trial 

According to a study recently published in The Lancet Haematology, carfilzomib-lenalidomide-dexamethasone (kCD) regimen did not meet non-inferiority criteria compared with bortezomib-based induction followed by high-dose melphalan and autologous hematopoietic stem-cell transplantation (HSCT) and lenalidomide maintenance among patients with newly diagnosed multiple myeloma (MM), although future studies are necessary to refine treatment approaches. 

Dr Kwee Yong, PhD, University College London, London, UK, and colleagues aimed to observe primary endpoints of partial response post-induction and progression-free survival rate, as well as safety of treatment as the secondary endpoint, in this randomized phase 2 CARDAMON trial. 

Between June 16, 2015 and July 8, 2019, 281 patients with a median age of 59 years and newly diagnosed and transplantation-eligible multiple myeloma (Eastern Cooperative Oncology Group performance status: 0 to 2) were enrolled in 19 hospitals across England and Wales. Patients received 4 28-day cycles of carfilzomib (56 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), cyclophosphamide (500 mg orally on days 1, 8, and 15), and dexamethasone (kCD [40 mg orally on days 1, 8, 15, and 22]) as induction therapy, followed by peripheral blood stem cell mobilization. 

The 218 patients who had at least a partial response to treatment were randomly assigned 1:1 to receive either high-dose melphalan plus autologous HSCT (n=109) or 4 cycles of kCD (n=109). Patients in both groups were administered 18 cycles of carfilzomib (56 mg/m2 intravenously on days 1, 8, and 15) as maintenance therapy). 7 patients withdrew before maintenance therapy (5 in the HSCT arm and 2 in the KCd arm). 

After induction therapy, 57.7% of patients (n=162) were observed to have at least a “very good partial response.” The progression-free survival rate at 2 years was 75% in the HSCT arm vs 68% in the kCD arm. These results indicate that kCD did not meet criteria for non-inferiority compared with HSCT. 

The most common grade 3 or 4 events during induction and consolidation in the KCd arm were lymphocytopenia and infection, and during carfilzomib maintenance therapy were hypertension and infection. Treatment-related serious adverse events were observed in 39% (n=109) of patients, with infections being the most common (29%). 2% (n=5) of patients died during induction, and 1 patient died during maintenance after HSCT. 

The results of this trial suggest that the carfilzomib-based treatment plan without autologous HSCT is not non-inferior to standard bortezomib-based induction followed by high-dose melphalan and autologous HSCT and lenalidomide maintenance among patients with multiple myeloma. Although endpoints were not met, Dr. Yong et al stated, “the marginal difference in progression-free survival suggests that further studies are warranted to explore deferred autologous HSCT in some subgroups, such as individuals who are MRD negative after induction.” 

Source: 

Yong K, Wilson W, Tute RM de, 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. The Lancet Haematology. 2023;10(2):e93-e106. doi:https://doi.org/10.1016/S2352-3026(22)00350-7