Selecting Between Quadruplet Induction Regimens

Selecting Between Quadruplet Induction Regimens

Data from the Perseus and Cassiopeia trials have informed quadruplet induction strategies, with minimal residual disease (MRD) serving as a key endpoint. Standardizing MRD testing requires institutional coordination, including integration into electronic medical record systems for consistent ordering. Earlier MRD negativity and higher rates of MRD negativity before transplant are achievable with quadruplet regimens, though the clinical significance of early MRD negativity continues to evolve.

Patient education regarding MRD testing emphasizes the sensitivity threshold of one myeloma cell per million normal cells. Historical transplant outcomes data combined with deep disease control before transplant may portend longer progression-free survival, though the impact of intensive post-transplant consolidation and maintenance remains unclear. The "sandwich" approach of using identical drugs before and after transplant is widely practiced, but optimal duration and intensity of post-transplant therapy require further study.

Concerns exist regarding premature treatment de-escalation based on early MRD negativity, as demonstrated by loss of MRD-negative status in studies that reduced therapy intensity too early. For transplant decisions, achieving partial response after four cycles of induction remains an acceptable endpoint to proceed with high-dose therapy, particularly given that MRD negativity rates after four cycles of quadruplet therapy remain around 20-25% at sensitive thresholds. The timing and durability of MRD negativity warrant longer follow-up before using it to guide treatment de-escalation in the first 6-12 months.