Evaluation of minimal residual disease (MRD) in the POLLUX and CASTOR trials showed that daratumumab-based regimens induced higher rates of sustained MRD negativity vs standard-of-care combination therapies, according to data from an exploratory analysis published in the Journal of Clinical Oncology.

The researchers evaluated sustained MRD negativity and outcomes from the phase 3 POLLUX trial (NCT02076009), which compared daratumumab, lenalidomide, and dexamethasone (D-Rd) with Rd, and the phase 3 CASTOR study (NCT02136134) of daratumumab, bortezomib, and dexamethasone (D-Vd) vs bortezomib and dexamethasone (Vd).

The investigators used next-generation sequencing to assess MRD at suspected complete response, at 3 months and 6 months after confirmed complete response (POLLUX), at 6 months and 12 months after the first dose (CASTOR), and every 12 months after complete response in both studies.

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Daratumumab-based regimens were found to induce a more than 4-fold higher MRD negativity rate vs combination control therapies in both studies. Specifically, the MRD negativity rate was 32.5% for D-Rd compared with 6.7% for Rd (P <.0001). MRD negativity was 15.1% for D-Vd compared with 1.6% for bortezomib and dexamethasone (Vd; P<.0001).

More patients in the intention-to-treat populations achieved sustained MRD negativity of 6 months or longer with D-Rd compared with Rd (20.3% vs 2.1%; P <.0001) and with D-Vd vs Vd (10.4% vs 1.2%; P <.0001). The same was true for sustained MRD negativity of 12 months or longer.

Patients who achieved MRD-negative status also had improved progression-free survival (PFS) compared with MRD-positive patients. Sustained MRD negativity was associated with improved PFS compared with MRD negativity in patients who initially achieved this status but did not maintain it.

“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,” the researchers concluded.

Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.


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. Published online January 29, 2021. doi:10.1200/JCO.20.01814