Validating DW-MRI and Fat Fraction in Multiple Myeloma Post-ASCT: The RAC-FAT Study"

Official title

Multicenter Observational Study for the Validation of the Predictive Role of Diffusion-Weighted Whole-body MRI (DW-MRI) Imaging Response According to MY-RADS Criteria (RAC Score) and Fat Fraction (rFF%) After Autologous Stem Cell Transplantation in Multiple Myeloma Patients Treated With First-Line Anti-CD38-Based Therapy (RAC-FAT Study)

Overview

This is a multicenter, observational, retrospective-prospective study designed to validate the predictive role of advanced imaging in patients with newly diagnosed multiple myeloma (NDMM). The main purpose of this study is to estimate the prevalence of radiological response categories (Response Assessment Category, RAC score) and evaluate the predictive value of relative Fat Fraction (rFF%) using Diffusion-Weighted Whole-Body Magnetic Resonance Imaging (DW-MRI) in patients who have undergone autologous stem cell transplantation (ASCT) after receiving first-line anti-CD38-based quadruplet induction therapy.

Detailed description

The role of functional imaging in Multiple Myeloma (MM) has become essential for assessing treatment response. This study focuses on the Myeloma Response Assessment and Diagnosis System (MY-RADS) guidelines and the quantitative parameter of rFF% to identify "functional high-risk" patients who may experience early relapse despite achieving conventional deep responses.The study will involve two cohorts:Retrospective Cohort: Includes patients treated since January 1st, 2020, with available post-ASCT DW-MRI data performed during routine clinical practice.Prospective Cohort: Includes newly diagnosed patients enrolled after their standard-of-care ASCT and post-transplant DW-MRI assessment.Participants will not receive any investigational or trial-specific treatment. All diagnostic and therapeutic procedures follow the current standard of care. Data regarding clinical characteristics, treatment details (induction, ASCT, maintenance), DW-MRI parameters (RAC score, apparent diffusion coefficient \[ADC\], and rFF% values), and minimal residual disease (MRD) will be collected and recorded in an anonymized electronic Case Report Form (eCRF).The study aims to enroll a minimum of 92 participants to evaluate:Primary Endpoint: Prevalence of RAC1 and RAC≥2 categories post-ASCT.Secondary Endpoints: Progression-free survival (PFS) and Overall Survival (OS) stratified by RAC score and rFF%, and the concordance between imaging results and bone marrow MRD.

Interventions

• Diagnostic test DW-MRI (MY-RADS/RAC score)
  Collection and analysis of Diffusion-Weighted Whole-body MRI data performed post-ASCT. The radiological response is evaluated using the Response Assessment Category (RAC) score (1 to 5) according to MY-RADS criteria.
• Diagnostic test Fat Fraction (rFF%)
  Quantitative assessment of the relative Fat Fraction (percentage of fat within skeletal regions) measured on residual focal lesions after transplantation to identify functional high-risk (FHR) patients.
• Other Clinical Data Collection
  Retrospective and prospective collection of clinical outcomes, including Progression-Free Survival (PFS), Overall Survival (OS), and Minimal Residual Disease (MRD) status from medical records.

Primary outcome measures

• Radiological Response Categories (RAC1 and RAC≥2) [Time frame: Post-ASCT / Pre-maintenance (approx. 3-4 months after ASCT))]

Secondary outcome measures (8)

• Progression-Free Survival (PFS) according to RAC score [Time frame: Minimum 2 years, up to 4 years]
• Overall Survival (OS) according to RAC score [Time frame: Minimum 2 years, up to 4 years]
• PFS and OS according to relative Fat Fraction (rFF%) [Time frame: Minimum 2 years, up to 4 years]
• RAC Score and IMWG Response Concordance [Time frame: 4 months post-ASCT]
• Concordance between RAC score and bone marrow MRD [Time frame: Pre-maintenance (approx. 100 days post-ASCT)]
• Early Relapse Rate and rFF% [Time frame: 18 months post-ASCT)]
• PFS by Combined MRD and RAC Score [Time frame: Through study completion, an average of 2 years]
• OS by Combined MRD and RAC Score [Time frame: Through study completion, an average of 2 years.]

Eligibility criteria

Inclusion criteria

• Newly diagnosed MM participants eligible for ASCT, treated with anti-CD38-based quadruplet induction therapy and ASCT, with post-ASCT/premaintenance DW-MRI available (in tandem ASCT, DW-MRI after second ASCT will be considered).
• Age ≥18 years.
• Participant must sign an informed consent form (ICF) that he or she understands the purpose of, and procedures required for the trial and is willing to participate in the trial.

Exclusion criteria

\- Absence of post-ASCT/pre-maintenance DW-MRI.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Other

Study locations

Italy · 10 centers

• IRCCS Istituto Tumori "G. Paolo II - U.O.C. Ematologia e Terapia Cellulare — Bari
• A.O.U. di Bologna - Policlinico S. Orsola Malpighi — Bologna
• A.O. Spedali Civili di Brescia — Brescia
• Istituto Oncologico Veneto IRCCS - UOC Oncoematologia — Castelfranco Veneto
• Ospedale Classificato Valduce — Como
• I.R.C.C.S. Ospedale S. Raffaele — Milan
• Ospedale Niguarda — Milan
• A.O.U. Maggiore della Carità — Novara
• … and 2 more centers

Identifiers

NCT: NCT07746232 · RAC-FAT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗