New evidence supports the use of a three drug combo—carfilzomib, lenolidomide, and dexamethasone (KRd), for maintenance therapy after autologous stem cell transplantation in patients newly diagnosed with multiple myeloma. Maintenance therapy using these three drugs may improve progression-free survival as compared to single agent lenalidomide treatment.
After almost 34 months in the study, median progression-free survival for the KRd arm was 59.1 months compared to 41.6 months for the lenalidomide arm. That’s a 49% reduction in the risk of progression or death. This reduction was despite a shorter duration (8 cycles) of treatment in 44% patients on the KRd arm.
Researchers from the University of Chicago Medicine Comprehensive Cancer Center and colleagues from the Polish Myeloma Consortium report the results, from the ongoing ATLAS trial, this month in Lancet Oncology. The study was led by Dominik Dytfeld, MD, PhD.
Overall, efficacy and toxicity results were favorable, making KRd a compelling consideration for post-transplant treatment after autologous stem-cell transplantation, said Andrzej Jakubowiak, MD, PhD, the Director of the Myeloma Program at the University of Chicago and the overall Principal Investigator of the ATLAS study.
Multiple myeloma is caused by rogue plasma cells producing a monoclonal immunoglobulin. These cells proliferate in the bone marrow and can cause osteolytic lesions, osteopenia, and fractures. Patients are categorized with standard-risk to high-risk disease based on fluorescence in situ hybridization (FISH) and other tests.
Treatment regimens are based on the stage of the disease. Those whose condition is most serious are candidates for autologous hematopoietic cell transplantation. Prior to transplantation, they undergo “induction therapy,” the goal of which is to reduce the number of rogue plasma cells prior to the procedure. The next step after the transplant is maintenance therapy.
But, “Many of the preferred treatment options have not been compared directly with each other in a randomized trial in these patient populations. As such, there is no standard of care and different experts use different regimens,” notes UpToDate in its latest post on multiple myeloma treatment.
As a result, various regimens and ways to guide their use are currently being evaluated in a number of ongoing randomized trials, including ATLAS—a phase 3 clinical study being conducted at 12 academic and clinical centers in the United States and Poland.
Between June 2016 and October 2020, this study enrolled 180 patients who were randomly assigned to receive either KRd or lenalidomide alone. Eligibility criteria included the completion of transplantation with no progression within twelve months from start of pre-transplantation therapy.
The KRd arm received either 8 or 36 cycles of KRd treatment based on minimal residual disease status and other risks for progression. Patients with standard risk disease who achieved MRD-negativity at the end of 6 cycles of KRd maintenance, received a total 8 cycles of KRd followed by lenalidomide maintenance. The remaining patients continued KRd for 36 cycles followed by lenalidomide maintenance.
The primary endpoint of the study was progression-free survival and secondary endpoints included MRD-negativity rates, safety, and tolerability.
Investigators note that these interim results are in line with those from the phase 2 FORTE trial, published in The Lancet in 2021. That study reported an improvement in progression-free survival, in the maintenance phase of the trial, with addition of carfilzomib to lenalidomide in comparison with lenalidomide alone.