Quadruplet Induction Therapy, ASCT and MRD-modulated Consolidation and Treatment Cessation

MASTER trial analysis in newly diagnosed multiple myeloma

Dr. Luciano Costa presented the final analysis of the MASTER trial at the European Hematology Association meeting in June 2023. The trial focused on a combination of four active myeloma drugs: dexamethasone, lenalidomide (Revlimid), carfilzomib (Kyprolis), and daratumumab (Darzalex). Patients received four cycles of this combination as induction therapy, followed by autologous transplant. The treatment after transplant was determined by achieving minimal residual disease (MRD) negativity. Patients with two consecutive MRD-negative readings transitioned to an observation phase without further therapy, while others received lenalidomide maintenance.

The data from the trial indicates that the outcomes for patients with zero or one high-risk abnormality treated with the quadruple therapy combination are excellent, with a majority achieving MRD negativity and maintaining stability without therapy. However, patients with ultra high-risk disease remain a challenge, and new drugs with different mechanisms of action, such as bi-specific T-cell engagers or CAR-T therapies, are needed to further improve outcomes for these patients.

• 81% of patients in the MASTER trial achieved some level of minimal residual disease (MRD) negativity.
• 71% of patients in the trial achieved two consecutive MRD-negative readings and transitioned to an observation phase without further therapy.
• Patients with two or more high-risk chromosome abnormalities were less likely to achieve a deeper level of MRD response.
• Patients with zero or one high-risk abnormality had over 85% progression-free survival at three years and over 92% overall survival.
• Patients with two or more high-risk abnormalities had lower survival rates, with a three-year progression-free survival of 50% and overall survival of 75%.
• Patients who achieved MRD negativity at some point post-transplant had similar prognoses compared to those who did not achieve it, suggesting extended therapy for MRD-positive patients may help improve outcomes.
• Patients who achieved two consecutive MRD-negative readings and stopped therapy had over 85% progression-free survival at three years and over 95% overall survival.
• Patients in the observation phase without subsequent therapy had the majority achieving and maintaining MRD negativity, but some experienced disease progression or MRD resurgence.
• Future trials in myeloma may need to test drugs with new mechanisms of action, such as bi-specific T-cell engagers or CAR-T therapies, to improve outcomes for patients with ultra high-risk disease.

Authors:
Luciano Costa, Eva Medvedova, Sarabh Chhabra, Bhagirathbhai Dholaria,  Binod Dhakal, Kelly Godby, Rebecca Silberman, Susan Bal, Anita D'Souza,  Smith Giri, Timothy Schmidt, James Omel, Parameswaran Hari, Natalie Callander