Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone

Circulating tumor cells (CTC) represent a high-risk biomarker in newly diagnosed multiple myeloma (NDMM); however, their prognostic value among transplant-eligible (TE) patients receiving daratumumab/bortezomib/lenalidomide/dexamethasone (D-VRd) remains unknown. In this study, we analyzed CTC in the phase 3 PERSEUS/EMN017 trial. TE-NDMM patients were randomized (1:1) to D-VRd with daratumumab/lenalidomide maintenance (D-VRd group) or bortezomib/lenalidomide/dexamethasone (VRd) with lenalidomide maintenance (VRd group), both with transplant. A subset of 451 of 709 patients from PERSEUS (D-VRd, 231/355; VRd, 220/354) had screening blood samples collected for CTC analysis by flow cytometry. CTC were detected in 370 patients (82%; median limit of detection, 0.0004%). CTC were prognostic of progression-free survival (PFS), independent of other factors, as a continuous (hazard ratio [HR], 1.36 [95% confidence interval (CI), 1.15-1.60]; P< .001) and categorical variable (≥0.175% CTC-high, optimal threshold). D-VRd improved PFS vs VRd in CTC-low patients (4-year rates: 88% vs 74%; HR, 0.42 [95% CI, 0.25-0.70]; P = .0013). Regardless of study treatment, minimal residual disease (MRD)-negativity rates were lower in CTC-high vs CTC-low patients (10-5: 52.2% vs 66.2%; 10-6: 34.8% vs 52.4%). D-VRd significantly increased MRD-negativity rates vs VRd among CTC-high (10-5: 69.4% vs 33.3%; 10-6: 47.2% vs 21.2%; both P< .05) and CTC-low patients (10-5: 74.4% vs 57.8%; 10-6: 65.6% vs 38.5%; both P< .001), with similar observations for sustained MRD-negativity. CTC levels are an independent prognostic factor in TE-NDMM treated with standard-of-care frontline quadruplet. D-VRd improved and sustained MRD-negativity rates in CTC-high and CTC-low, and improved PFS for CTC-low with a positive trend in CTC-high patients. This trial was registered at www.clinicaltrials.gov as #NCT03710603.

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Journal
Blood
Published
2025-10-08
DOI
https://doi.org/10.1182/blood.2025030113
Citations
4
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
Field-Weighted Citation Impact
7.08

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article

Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone

Andrew Spencer, Pieter Sonneveld, Mattia D’Agostino, Cathelijne Fokkema et al.
4 citations
Blood
Multiple Myeloma Research and Treatments
7.08
article

Circulating tumor cells predict myeloma outcomes in patients treated with daratumumab, bortezomib, lenalidomide, and dexamethasone

Andrew Spencer, Pieter Sonneveld, Mattia D’Agostino, Cathelijne Fokkema, Hermann Einsele, Paweł Robak, Mario Boccadoro, Christoph Driessen, Vincent H. J. van der Velden, Niels W.C.J. van de Donk, Evangelos Terpos, Diego Vieyra, Ricardo M. Attar, Richard G. Carson, Annemiek Broijl, Tom Cupedo, Annette Juul Vangsted, Anna Sitthi-Amorn, Fredrik Schjesvold, Luca Bertamini, Meral Beksaç, Paula Rodríguez‐Otero, Mark van Duin, Roman Hájek, Michel Delforge, Philippe Moreau
article en
4 citations

Abstract

Circulating tumor cells (CTC) represent a high-risk biomarker in newly diagnosed multiple myeloma (NDMM); however, their prognostic value among transplant-eligible (TE) patients receiving daratumumab/bortezomib/lenalidomide/dexamethasone (D-VRd) remains unknown. In this study, we analyzed CTC in the phase 3 PERSEUS/EMN017 trial. TE-NDMM patients were randomized (1:1) to D-VRd with daratumumab/lenalidomide maintenance (D-VRd group) or bortezomib/lenalidomide/dexamethasone (VRd) with lenalidomide maintenance (VRd group), both with transplant. A subset of 451 of 709 patients from PERSEUS (D-VRd, 231/355; VRd, 220/354) had screening blood samples collected for CTC analysis by flow cytometry. CTC were detected in 370 patients (82%; median limit of detection, 0.0004%). CTC were prognostic of progression-free survival (PFS), independent of other factors, as a continuous (hazard ratio [HR], 1.36 [95% confidence interval (CI), 1.15-1.60]; P< .001) and categorical variable (≥0.175% CTC-high, optimal threshold). D-VRd improved PFS vs VRd in CTC-low patients (4-year rates: 88% vs 74%; HR, 0.42 [95% CI, 0.25-0.70]; P = .0013). Regardless of study treatment, minimal residual disease (MRD)-negativity rates were lower in CTC-high vs CTC-low patients (10-5: 52.2% vs 66.2%; 10-6: 34.8% vs 52.4%). D-VRd significantly increased MRD-negativity rates vs VRd among CTC-high (10-5: 69.4% vs 33.3%; 10-6: 47.2% vs 21.2%; both P< .05) and CTC-low patients (10-5: 74.4% vs 57.8%; 10-6: 65.6% vs 38.5%; both P< .001), with similar observations for sustained MRD-negativity. CTC levels are an independent prognostic factor in TE-NDMM treated with standard-of-care frontline quadruplet. D-VRd improved and sustained MRD-negativity rates in CTC-high and CTC-low, and improved PFS for CTC-low with a positive trend in CTC-high patients. This trial was registered at www.clinicaltrials.gov as #NCT03710603.

BloodVol. 147(4)
Oslo University Hospital (NO), Johnson & Johnson (United States) (US), University of Ostrava (CZ), National and Kapodistrian University of Athens (GR), Erasmus MC (NL), Rigshospitalet (DK), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), University Hospital Ostrava (CZ), Monash Alfred Psychiatry Research centre (AU), Springhouse (US), Copernicus Memorial Hospital (PL), Istinye University (TR), Universitätsklinikum Würzburg (DE), Hôtel-Dieu de Paris (FR), Clinica Universidad de Navarra (ES), Erasmus MC Cancer Institute (NL), Janssen (United States) (US), Amsterdam University Medical Centers (NL), Liv Hospital (TR), Department of Public Health (US), Ostschweizer Kinderspital (CH), University of Turin (IT), Monash University (AU), Vrije Universiteit Amsterdam (NL), Erasmus University Rotterdam (NL), KU Leuven (BE)
Amgen, Pfizer, AstraZeneca, Sanofi, Yale University, Celgene, Regeneron Pharmaceuticals, Adaptive Biotechnologies, Celltrion, SkylineDx, PharmaMar, EUSA Pharma, Raymond and Beverly Sackler Institute for Biological, Physical and Engineering Sciences, Yale University, Daiichi Sankyo Europe, Cilag
Openalex Percentile: Top 3%
Multiple Myeloma Research and Treatments
7.08
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