Researchers from the University of Chicago Medicine Comprehensive Cancer Center and colleagues in Poland report promising results from their ongoing ATLAS trial, published on January 12, 2023 in the journal Lancet Oncology.
The results of this study indicate that maintenance therapy (a term researchers use to describe therapy with aim to preventing disease progression or death) with a combination of three drugs, carfilzomib, lenalidomide, and dexamethasone (known as KRd) may improve progression-free survival (a term clinicians use to describe the time to disease progression or death) when compared to the current standard of single agent lenalidomide treatment in patients with newly diagnosed multiple myeloma who have undergone initial induction treatment followed by autologous stem cell transplantation.
The ATLAS trial, is an investigator-initiated, open-label, randomized, phase 3 clinical study conducted at 12 academic and clinical centers in the United States and in Poland. Between June 10, 2016 and October 21, 2020, the study enrolled 180 patients who were randomly assigned to receive either KRd or lenalidomide alone. The key eligibility criteria included the completion of transplantation after any initial pre-transplantation therapy with no progression within twelve months from initiation of pre-transplantation therapy.
The KRd arm received either 8 or 36 cycles of KRd treatment based on the minimal residual disease (MRD) status - the amount of cancer cells that remain in the body during or after treatment - and presence or absence of disease risks for progression. Patients who had standard risk disease and 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 the secondary endpoints included MRD-negativity rates, safety, and tolerability.
After median follow-up of 33.8 months, median progression-free survival for the KRd arm was 59.1 months compared to 41.6 months for the lenalidomide arm, which represents a 49% reduction in the risk of progression or death. This risk reduction was observed despite a shorter duration (8 cycles) of KRd treatment in 44% patients on the KRd arm with standard risk and MRD-negativity after cycle 6. The improvement of progression-free survival was associated with higher rate of MRD-negativity in the KRd arm compared to the lenalidomide arm at the completion of 6 cycles (53% vs 31%). As expected, patients in the KRd-treated arm experienced higher rates of toxicity but the differences did not translate into higher rates of treatment discontinuation or dose reductions, the authors noted. Based on these results, investigators concluded that MRD- and risk-adapted KRd can be considered as a new option for post-transplant maintenance in newly diagnosed myeloma.
