Multiple Myeloma (MM)
Conditions
Keywords
Newly diagnosed multiple myeloma (NDMM), Transplant-eligible (TE), Diffusion-weighted whole-body MRI (DW-MRI), MY-RADS criteria, Response Assessment Category (RAC score), Fat Fraction (rFF%), Autologous Stem Cell Transplantation (ASCT), Anti-CD38-based therapy
Brief summary
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_TESTDW-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_TESTFat 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.
Retrospective and prospective collection of clinical outcomes, including Progression-Free Survival (PFS), Overall Survival (OS), and Minimal Residual Disease (MRD) status from medical records.
Sponsors
Fondazione EMN Italy Onlus
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiological Response Categories (RAC1 and RAC≥2) | Post-ASCT / Pre-maintenance (approx. 3-4 months after ASCT)) | Prevalence of radiological response categories evaluated by post-ASCT DW-MRI according to MY-RADS criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) according to RAC score | Minimum 2 years, up to 4 years | Defined as the time from the date of ASCT to the first documented disease progression (per IMWG criteria) or death from any cause. |
| Overall Survival (OS) according to RAC score | Minimum 2 years, up to 4 years | Defined as the time from the date of ASCT to death from any cause. |
| PFS and OS according to relative Fat Fraction (rFF%) | Minimum 2 years, up to 4 years | Evaluation of survival outcomes based on the 17.2% rFF% threshold identified on residual focal skeletal lesions. |
| RAC Score and IMWG Response Concordance | 4 months post-ASCT | To assess RAC score in relation to response according to IMWG criteria |
| Concordance between RAC score and bone marrow MRD | Pre-maintenance (approx. 100 days post-ASCT) | Assessment of the agreement between radiological response (RAC score) and Minimal Residual Disease (MRD) status (when available). |
| Early Relapse Rate and rFF% | 18 months post-ASCT) | Proportion of participants with early relapse (within 18 months post-ASCT) associated with rFF% \< 17.2%. |
| OS by Combined MRD and RAC Score | Through study completion, an average of 2 years. | Evaluation of post-ASCT overall survival (OS) stratified by the combined assessment of bone marrow minimal residual disease (MRD) status and radiological Response Assessment Category (RAC) score. |
| PFS by Combined MRD and RAC Score | Through study completion, an average of 2 years | Evaluation of post-ASCT progression-free survival (PFS) stratified by the combined assessment of bone marrow minimal residual disease (MRD) status and radiological Response Assessment Category (RAC) score. |
Countries
Italy
Contacts
CONTACTFONDAZIONE EMN ITALY ETS FONDAZIONE EMN ITALY ETS
Outcome results
None listed