In prior clinical trials, daratumumab has shown significant improvements in progression-free survival (PFS) and overall response rate when used in combination with lenalidomide (R)/dexamethasone (d) and bortezomib (V)/dexamethasone, respectively.1,2 To determine the ability of daratumumab to drive deep clinical responses beyond complete response (CR), minimal residual disease (MRD) was assessed in both POLLUX and CASTOR, and presented at the 2016 ASH Annual Meeting.
MRD was assessed in POLLUX at the time of suspected CR, and at 3 and 6 months post-suspected CR for patients who maintained response. Similarly, in CASTOR, MRD was assessed for patients at the time of suspected CR and at 6 months and 12 months after the first dose. The MRD-negative rate per treatment arm was determined as the proportion of patients with negative MRD at any time point after the first dose. The addition of daratumumab to Rd in POLLUX or Vd in CASTOR resulted in significantly higher MRD-negative rates at all 3 thresholds examined (10-4, 10-5, and 10-6). Patients with sustained MRD negativity over time also showed significantly longer PFS with daratumumab + Rd or Vd than with Rd or Vd alone.
These 2 groundbreaking studies represent the first randomized, controlled, prospective evaluation of MRD in the relapsed/refractory multiple myeloma phase 3 clinical trial setting. In the study, daratumumab-containing therapies consistently demonstrated greater MRD-negative rates compared with the control groups at all evaluated thresholds. Because MRD-negative patients treated with daratumumab had longer PFS than patients treated with Rd or Vd alone, the authors concluded that the deep clinical responses induced by daratumumab may also lead to improved survival.
Avet-Loiseau H, et al. ASH 2016. Abstract 246.
- Dimopoulos MA, et al. N Engl J Med. 2016; in press.
- Palumbo A, et al. N Engl J Med. 2016; in press.