Carfilzomib, Lenalidomide, and Dexamethasone Therapy Improved PFS Among Patients With Multiple Myeloma

Results from the Randomized Phase 3 ATLAS Trial

According to the randomized, phase 3 ATLAS trial recently published in The Lancet Oncology, carfilzomib, lenalidomide, and dexamethasone maintenance therapy improved progression-free survival (PFS) among patients with multiple myeloma (MM) compared to the use of lenalidomide alone. However, lenalidomide alone produced less risk for adverse events than when combined with the other maintenance therapies. 

Dr Dominik Dytfeld and coauthors stated, “lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation,” which led them to compare it alone vs in combination with other maintenance therapies in this study to evaluate endpoints of progression-free survival, safety, and efficacy. 

The ATLAS trial was an investigator-initiated, multicenter, open-label, phase 3 study conducted at 12 centers in the USA and Poland. Between June 10, 2016, and October 21, 2020, 180 patients with a median age of 59 who had newly diagnosed multiple myeloma after autologous stem cell transplant (ASCT) were randomly assigned to receive a combination of carfilzomib, lenalidomide, and dexamethasone (n=93) or lenalidomide alone (n=87). They were to continue therapy for 36 cycles, or until disease progression or unacceptable toxicity was observed. After cycles were completed, both arms received lenalidomide treatment as maintenance. 

At a median follow-up of 33.8 months, the median progression-free survival was 59.1 months in the carfilzomib, lenalidomide, and dexamethasone arm vs 41.4 months in the lenalidomide arm. Serious treatment-related adverse events were observed in 30% (n=28) of patients in the carfilzomib, lenalidomide, and dexamethasone arm vs 22% (n=19) in the lenalidomide arm, and led to 1 death in the carfilzomib, lenalidomide, and dexamethasone arm. The most prevalent grade 3 or 4 adverse events were neutropenia (48% in the carfilzomib, lenalidomide, and dexamethasone arm vs 60% in the lenalidomide group), thrombocytopenia (13% vs 7%), and lower respiratory tract infections (8% vs 1%). 

As primary endpoints were met, Dr Dytfeld et al concluded that their study “provides support for considering carfilzomib, lenalidomide, and dexamethasone therapy in patients with newly diagnosed multiple myeloma who completed any induction regimen followed by autologous stem-cell transplantation.” Evaluation of the safety of the treatment is necessary for ongoing studies. 

Source: 

Dytfeld D, Wróbel T, Jamroziak K, et al. Carfilzomib, lenalidomide, and dexamethasone or lenalidomide alone as maintenance therapy after autologous stem-cell transplantation in patients with multiple myeloma (ATLAS): interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(2):139-150. doi:https://doi.org/10.1016/S1470-2045(22)00738-0