Study Shows Carfilzomib Combo Boosts Survival in Newly Diagnosed Multiple Myeloma Patients Post-Transplant
The phase 3 ATLAS trial (NCT02659293) conducted an unplanned interim analysis to evaluate the efficacy of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone (KRd) compared to lenalidomide alone in patients with newly diagnosed multiple myeloma who underwent autologous stem cell transplant (ASCT) after induction therapy. The results showed a significant improvement in progression-free survival (PFS) with KRd, but no difference in overall survival (OS).
After a median follow-up of 33.8 months, the median PFS was 59.1 months with KRd compared to 41.4 months with lenalidomide alone. This translates to a hazard ratio (HR) of 0.51, indicating a 49% reduction in the risk of disease progression or death with KRd (P = .012). However, there was no significant difference in OS between the two treatment arms, with a HR of 0.83 (P = .68). The median OS was not reached in the experimental arm, while it was 61.8 months in the control arm.
These findings suggest that maintenance therapy with KRd can significantly improve PFS in patients with newly diagnosed multiple myeloma who have undergone ASCT after induction therapy. However, it does not have a significant impact on overall survival. Further research and longer follow-up are needed to fully understand the implications of these results.
The authors of the publication stated that in the ATLAS study’s interim analysis, they demonstrated that a treatment approach targeting minimal residual disease (MRD) and adjusting for risk using carfilzomib, lenalidomide, and dexamethasone for 8 to 36 cycles may provide a progression-free survival (PFS) advantage compared to lenalidomide alone as maintenance therapy after autologous stem cell transplantation (ASCT) in patients with newly diagnosed multiple myeloma.
In patients with newly diagnosed multiple myeloma who are eligible for transplantation, the standard of care involves lenalidomide maintenance following induction therapy and ASCT. Previous attempts to enhance PFS and overall survival (OS) after transplantation through short consolidation therapy or tandem transplant have yielded mixed results. However, emerging evidence from two phase 2 trials (NCT01816971; NCT02203643) suggests that the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) may be more effective than lenalidomide maintenance alone.
To be eligible for enrollment in this trial, patients had to be at least 18 years old and have newly diagnosed multiple myeloma. They also had to have completed any type of induction therapy followed by a single ASCT. Additionally, patients needed to have stable disease or better, received the transplant within 100 days, initiated induction therapy 12 months before enrollment, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, an absolute neutrophil count of at least 1 × 10⁹ cells/L, a platelet count of at least 70 × 10⁹ platelets/L, adequate liver function, and a creatinine clearance of at least 50 mL/min or a serum creatinine level lower than 2 mg/dL.