Achieving a deeper response is associated with better progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (RRMM) or transplant-ineligible, newly diagnosed multiple myeloma (TIE NDMM), according to research published in Blood

Researchers found that achieving a complete response (CR) or better with minimal residual disease (MRD) negativity was linked to improved PFS, regardless of the treatment received or the disease setting. 

For this study, researchers analyzed patients with RRMM or TIE NDMM who were enrolled in 4 phase 3 studies — POLLUX ( Identifier: NCT02076009), CASTOR ( Identifier: NCT02136134), ALCYONE ( Identifier: NCT02195479), and MAIA ( Identifier: NCT02252172).

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A total of 2510 patients were evaluated — 569 patients in POLLUX, 498 in CASTOR, 706 in ALCYONE, and 737 in MAIA. In each trial, patients were randomly assigned to receive daratumumab plus standard care or standard care alone. 

Baseline demographics and clinical characteristics were generally well balanced between the treatment arms in each trial. The median follow-up was 54.8 months in POLLUX, 50.2 months in CASTOR, 40.1 months in ALCYONE, and 36.4 months in MAIA. 


In the combined analysis of all patients, those who achieved at least a CR with MRD negativity had longer PFS compared with those who were MRD positive or achieved a very good partial response (VGPR) or less. The 48-month PFS rate was 70.4% and 23.9%, respectively (HR, 0.20; 95% CI, 0.16-0.24; P <.0001). 

The researchers also analyzed a subgroup of patients that included those with TIE NDMM and patients with RRMM who had received 2 prior lines of therapy or fewer. In this group, the 48-month PFS rate was 70.7% for patients who achieved at least a CR and MRD negativity, compared with 24.8% for patients who were MRD positive or achieved a VGPR or less (HR, 0.20; 95% CI, 0.16-0.25; P <.0001). 

The benefit of achieving a CR and MRD negativity was observed regardless of treatment regimen or disease setting, the researchers noted. However, patients who achieved deeper responses had better PFS if they received daratumumab-based treatments.

Daratumumab-based therapies were associated with significantly improved PFS in the pooled analysis of all patients (HR, 0.55; 95% CI, 0.36-0.84; P =.0057) and in the subgroup of TIE NDMM patients and those with RRMM who had received 2 prior lines of therapy or fewer (HR, 0.54; 95% CI, 0.35-0.83; P =.0055).

“These findings represent the first large-scale analysis with robust methodology to support ≥CR with MRD negativity as a prognostic factor for PFS in RRMM and TIE NDMM,” the researchers wrote.

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.


Cavo M, San-Miguel J, Usmani SZ, et al. Prognostic value of minimal residual disease negativity in myeloma: Combined analysis of POLLUX, CASTOR, ALCYONE, and MAIA. Blood. February 10, 2022. doi:10.1182/blood.2021011101