Adding daratumumab to treatment with lenalidomide and dexamethasone extends overall survival (OS) in patients with relapsed or refractory multiple myeloma (MM), according to research published in the Journal of Clinical Oncology.
The final analysis of the phase 3 POLLUX trial showed that daratumumab plus lenalidomide and dexamethasone (D-Rd) improved OS across subgroups, when compared with lenalidomide and dexamethasone (Rd) alone. No new safety signals were reported.
The POLLUX trial (ClinicalTrials.gov Identifier: NCT02076009) included 569 patients with relapsed or refractory MM who had received at least 1 prior line of therapy. The patients were randomly assigned to receive D-Rd (n=286) or Rd (n=283) until disease progression or unacceptable toxicity.
At the final analysis, the median follow-up was 79.7 months. The median OS was 67.6 months with D-Rd and 51.8 months with Rd alone, which translated to a 27% reduction in the risk of death (hazard ratio [HR], 0.73; 95% CI, 0.58-0.91; P =.0044).
“This updated analysis of the POLLUX study reports the longest median overall survival observed to date in phase III studies of Rd-based triplets in RR [relapsed/refractory] MM,” the researchers wrote.
The OS benefit with D-Rd vs Rd was seen in:
- Patients with 1 prior line of therapy (median OS, 77.8 months with D-Rd vs 57.7 months with Rd)
- Patients with 2 prior lines of therapy (53.1 months vs 45.4 months)
- Patients with 3 prior lines of therapy (59.0 months vs 52.0 months)
- Patients aged 65 years and older (53.1 months vs 49.9 months)
- Patients with high-risk cytogenetics (40.0 months vs 23.6 months).
After the positive primary analysis, patients assigned to the Rd arm could receive daratumumab monotherapy after disease progression, and 122 patients went on to receive a daratumumab-containing regimen. Of these patients, 66 received single-agent daratumumab as part of the study protocol. The median OS for these patients was 65.6 months, and about a third (36.4%) were still alive at the final analysis.
“We recognize that treatment options for relapsed or refractory multiple myeloma have moved beyond daratumumab monotherapy in more recent years and allowing subsequent therapy may confound OS results,” the researchers wrote. “Nevertheless, an OS advantage was observed with D-Rd over Rd despite patients in the Rd arm receiving subsequent daratumumab therapy.”
No new safety concerns were reported with extended follow-up. The proportion of patients who discontinued treatment due to treatment-emergent adverse events was comparable between the arms (19.1% in the D-Rd arm and 16.0% in the Rd arm).
“Triplets such as D-Rd are superior to doublets such as Rd alone and therefore should be the SOC [standard of care] in patients with relapsed [or] refractory multiple myeloma,” noted Journal of Clinical Oncology Associate Editor Suzanne Lentzsch, MD, PhD, in a comment on the results.
Disclosures: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Dimopoulos MA, Oriol A, Nahi H, et al. Overall survival with daratumumab, lenalidomide, and dexamethasone in previously treated multiple myeloma (POLLUX): A randomized, open-label, phase III trial.J Clin Oncol. Published online January 4, 2023. doi:10.1200/JCO.22.00940