Daratumumab Combos Sustained MRD Negativity for Patients with Relapsed/Refractory Multiple Myeloma

Combination regimens containing daratumumab (Darzalex) sustained minimal residual disease (MRD) negativity at higher rates than standard-of-care comparators for patients with relapsed and/or refractory multiple myeloma (RRMM), according to data published in the Journal of Clinical Oncology.

MRD negativity is associated with durable remissions and prolonged clinical outcomes, and these data regarding daratumumab-containing regimens could potentially help in determining if MRD negativity can serve as a predictive and prognostic end point for clinical outcomes.

“Patients in the RRMM setting who achieved CR [complete response] or better and MRD-negative status had prolonged PFS [progression-free survival] compared with patients who did not,” wrote the investigators. “In addition, daratumumab-based regimens enabled many patients with RRMM to attain deep and sustained MRD-negative responses, resulting in longer periods without disease progression.”

Sustained MRD negativity and outcomes were evaluated in both the POLLUX (NCT02076009) and the CASTOR (NCT02136134) trials. POLLUX tested the combination of lenalidomide (Revlimid) and dexamethasone with (D-Rd) or without daratumumab (Rd), while CASTOR tested bortezomib (Velcade) and dexamethasone with (D-Vd) or without daratumumab (Vd).

Focusing on the intention-to-treat population, the MRD negativity rates were 32.5% for the D-Rd combination compared with 6.7% for treatment with Rd (P < .0001). For D-Vd treatment, the MRD negativity rate was 15.1% compared with 1.6% for Vd (P < .0001).

More, higher MRD negativity rates were observed in the group of patients experiencing a CR or better for the combination treatments in both the POLLUX (D-Rd, 57.4% vs Rd, 29.2%; P = .0001) and CASTOR trials (D-Vd, 52.8% vs Vd, 17.4%; P = .0035).

At 6 or more months, the research team found that more patients achieved sustained MRD negativity when treated with D-Rd (20.3%) compared with Rd (2.1%; P < .0001) and D-Vd (10.4%) compared with Vd (1.2%; P < .0001). The same trend was analyzed at 12 or more months, with MRD negativity rates higher with D-Rd (16.1%) and D-Vd (6.8%) compared with Rd (1.4%; P < .0001) and Vd (0%), respectively.

“Sustained MRD negativity was associated with improved PFS compared with patients who obtained MRD-negative status but did not maintain MRD durability,” wrote the investigators. “Although the benefit of MRD negativity and durability occurred regardless of therapy, daratumumab-containing regimens enabled a higher proportion of patients to achieve deep and durable responses.”

Median follow-up time for the research was 54.8 months in the POLLUX study and 50.2 months in the CASTOR study.

The investigators utilized next-generation sequencing at suspected complete response to measure MRD. Sustained MRD negativity was measured for both 6 and 12 or more months follow-up.

“Achieving durable MRD negativity may predict long-term outcomes, as durable MRD negativity improves PFS and increases the time between treatment relapses for RRMM,” wrote the investigators.

Reference:

Avet-Loiseau H, San-Miguel J, Casneuf T, et al. Evaluation of Sustained Minimal Residual Disease Negativity With Daratumumab- Combination Regimens in Relapsed and/or Refractory Multiple Myeloma: Analysis of POLLUX and CASTOR. J Clin Oncol. January 29, 2021. doi:10.1200/JCO.20. 01814