MRD-guided Dara-KRd induction in NDMM: A phase II trial

Achieving and maintaining sustained undetectable MRD translates into improved outcomes for patients with MM; however, data are limited on how to integrate MRD status in guiding treatment decisions. Results from a phase II trial (NCT04113018) evaluating an MRD-guided Dara-KRd induction regimen in NDMM were published by Bhutani et al. in Blood Advances.¹

A total of 36 patients completed induction and were divided into three groups post-induction: Group A (MRD negative, n = 24), Group B (MRD positive, transplant eligible, n = 8), and Group C (MRD positive, transplant ineligible, n = 4). The primary endpoint was rate of responses ≥CR or sCR at the end of Dara-KRd induction. Secondary endpoints included MRD negativity post-induction and safety. 

At the end of induction, 53.8% of patients achieved ≥CR (90% CI: 39.6–67.7; p = 0.375), including 41% who achieved sCR.

MRD negativity rates were 59% and 41% post-induction, and 77% and 72% at any time point, by NGS at sensitivities of 10^-5 and 10^-6, respectively. In Group B, 62.5% of patients were MRD negative at 10^-5 after auto-HSCT, 3 of whom were also MRD negative at 10^-6.

At least 1 TEAE was reported in all patients. SAEs were noted in 38.5% of patients, of which 23.1% were treatment-related SAEs. 

Although the trial did not meet the primary endpoint, high rates of ≥CR and MRD negativity were achieved with Dara-KRd, and no new safety signals were identified. The post-induction MRD-guided approach deepened responses in patients who were MRD-positive and maintained durable MRD control in those who were MRD-negative.