Impact of minimal residual disease standardised assessment by FDG-PET/CT in transplant-eligible patients with newly diagnosed multiple myeloma enrolled in the imaging sub-study of the FORTE trial

Elena Zamagni; Stefania Oliva; Francesca Gay; Andrea Capra; Delia Rota-Scalabrini; Mattia D'Agostino; Angelo Belotti; Monica Galli; Manuela Racca; Renato Zambello; Barbara Gamberi; Domenico Albano; Luca Bertamini; Annibale Versari; Mariella Grasso; Nicola Sgherza; Claudia Priola; Francesca Fioritoni; Francesca Patriarca; Gabriella De Cicco; Tania Villanova; Anna Pascarella; Pietro Zucchetta; Paola Tacchetti; Stefano Fanti; Katia Mancuso; Simona Barbato; Mario Boccadoro; Pellegrino Musto; Michele Cavo; Cristina Nanni

doi:10.1016/j.eclinm.2023.102017

Impact of minimal residual disease standardised assessment by FDG-PET/CT in transplant-eligible patients with newly diagnosed multiple myeloma enrolled in the imaging sub-study of the FORTE trial

EClinicalMedicine. 2023 Jun 9:60:102017. doi: 10.1016/j.eclinm.2023.102017. eCollection 2023 Jun.

Authors

Elena Zamagni^{1

2}, Stefania Oliva³, Francesca Gay^{3

4}, Andrea Capra⁴, Delia Rota-Scalabrini⁵, Mattia D'Agostino^{3

4}, Angelo Belotti⁶, Monica Galli⁷, Manuela Racca⁸, Renato Zambello⁹, Barbara Gamberi¹⁰, Domenico Albano¹¹, Luca Bertamini^{3

4}, Annibale Versari¹², Mariella Grasso¹³, Nicola Sgherza¹⁴, Claudia Priola⁴, Francesca Fioritoni¹⁵, Francesca Patriarca¹⁶, Gabriella De Cicco^{1

2}, Tania Villanova⁴, Anna Pascarella¹⁷, Pietro Zucchetta¹⁸, Paola Tacchetti¹, Stefano Fanti¹⁹, Katia Mancuso^{1

2}, Simona Barbato^{1

2}, Mario Boccadoro⁴, Pellegrino Musto^{14

20}, Michele Cavo^{1

2}, Cristina Nanni¹⁹

Affiliations

¹ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
² Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy.
³ Division of Hematology, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
⁴ Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
⁵ Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Torino, Italy.
⁶ Department of Hematology, ASST Spedali Civili di Brescia, Brescia, Italy.
⁷ UO Hematology, ASST Papa Giovanni XXIII, Bergamo, Italy.
⁸ Nuclear Medicine Unit, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
⁹ Department of Medicine (DIMED), Hematology and Clinical Immunology, Padua University, Padua, Italy.
¹⁰ Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, Italy.
¹¹ Nuclear Medicine Department, University of Brescia and ASST Spedali Civili Brescia, Brescia, Italy.
¹² Nuclear Medicine Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
¹³ Azienda Ospedaliera S. Croce-Carle, Cuneo, Italy.
¹⁴ Hematology and Stem Cell Transplantation Unit, AOU Consorziale Policlinico, Bari, Italy.
¹⁵ Ospedale Santo Spirito, Pescara, Italy.
¹⁶ Hematologic Clinic and Transplant Center, University Hospital of Central Friuli, DAME, University of Udine, Udine, Italy.
¹⁷ UOC Ematologia, Ospedale dell'Angelo, Venezia Mestre, Italy.
¹⁸ Nuclear Medicine Unit, Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy.
¹⁹ Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
²⁰ Department of Precision and Regenerative Medicine and Ionian Area, "Aldo Moro" University School of Medicine, Bari, Italy.

Abstract

Background: 18F-FDG-PET/CT is the current standard technique to define minimal residual disease (MRD) outside the bone marrow (BM) in multiple myeloma (MM), recently standardised applying the Deauville scores (DS) to focal lesions (FS) and bone marrow uptake (BMS) and defining the complete metabolic response (CMR) as uptake below the liver background (DS <4).

Methods: In this analysis, we aimed at confirming the role of CMR, and complementarity with BM multiparameter flow cytometry (MFC) at 10^-5, in an independent cohort of newly diagnosed transplant-eligible MM patients previously enrolled in the phase II randomised FORTE trial. 109 of the 474 global patients enrolled in the trial between February 23, 2015, and April 5, 2017, who had paired PET/CT (performed at baseline [B] and preceding maintenance therapy [PM]) and MFC evaluation, were included in this analysis.

Findings: At B, 93% of patients had focal lesions within the bones (FS ≥4 in 89%) and 99% increased BM uptake (BMS ≥4 in 61%). At PM, CMR was achieved in 63% of patients, which was a strong predictor for prolonged PFS in univariate analysis at landmark time PM (HR 0.40, P = 0.0065) and in Cox multivariate analysis (HR 0.31, P = 0.0023). Regarding OS, a trend in favour of CMR was present in univariate (HR 0.44, P = 0.094), and Cox multivariate model (HR 0.17, P = 0.0037). Patients achieving both PET/CT CMR and MFC negativity at PM showed significantly extended PFS in univariate (HR 0.45, P = 0.020) and multivariate analysis (HR 0.41, P = 0.015).

Interpretation: We herein confirm the applicability and validity of DS criteria to define CMR and its prognostic relevance and complementarity with MFC at the BM level.

Funding: Amgen, Celgene/Bristol Myers Squibb, Italian Ministry of Health (RC-2022-2773423).

Keywords: Complete metabolic response (CMR); FDG-PET/CT; Minimal residual disease (MRD); Multiparameter flow cytometry (MFC); Newly diagnosed multiple myeloma (NDMM).