Prospective Evaluation of MRI and PET-CT at Diagnosis and before Maintenance Therapy in Symptomatic Patients with Multiple Myeloma Included in the IFM/DFCI 2009 Trial
Authors: Moreau Philippe , Attal Michel , Karlin Lionel , Garderet Laurent , Facon Thierry , Benboubker Lotfi , Macro Margaret , Caillot Denis , Escoffre-Barbe Martine , Stoppa Anne-Marie , Laribi Kamel , Hulin Cyrille , Marit Gerald , Eveillard Jean-Richard , Caillon Florence , bodet-Millin Caroline , Nguyen jean-Michel , Pegourie Brigitte , Dorvaux Veronique , Chaleteix Carine , Dupas Benoit , Bodere Françoise 
Published: October 2019

Abstract
Introduction
Magnetic resonance imaging (MRI) of the spine and the pelvis is an important tool to evaluate bone disease in patients with symptomatic multiple myeloma (MM) at the time of diagnosis. In the context of high-dose therapy and autologous stem cell transplantation (ASCT), it has also been reported that the number of MRI focal lesions (> 7) and the presence of diffuse pattern correlate with inferior survival (Walker et al. J Clin Oncol; 25:1121-1128 2007). MRI might help in the better definition of complete response (CR). However, the high number of false positive results suggests that another imaging method, such as Positron emission tomography combined with computed tomography using fluoro-deoxy-glucose (PET-CT), might be of more value in this setting. Moreover, imaging techniques have rarely been compared to minimal residual disease (MRD) evaluated by flow cytometry from bone marrow aspiration in the context of frontline therapy including novel agents and ASCT. The goal of our study was to compare prospectively MRI and PET-CT at 3 different time-points, at diagnosis, after 3 cycles of triplet induction therapy and prior to maintenance therapy in a group of patients enrolled into IFM-DFCI 2009 trial comparing frontline or delayed ASCT.
Patients and methods
In the prospective IFM-DFCI 2009 trial, 700 patients with de novo symptomatic MM eligible for high-dose therapy have been randomized in France and Belgium to receive either 8 cycles of bortezomib-lenalidomide-dexamethasone (VRD) followed by 1-year maintenance with lenalidomide, or 3 cycles of VRD followed by high-dose therapy and ASCT plus 2 cycles of VRD consolidation and 1-year lenalidomide maintenance. 134 / 700 patients were also included in the IMAJEM trial (NCT01309334, also supported by STIC program granted by the French NCI) aimed at comparing in both arms of the IFM-DFCI 2009 study spine and pelvis MRI and whole-body PET-CT at diagnosis (number of lesions, primary end-point), after 3 cycles of VRD, and prior to maintenance (prognosis impact of imaging negativity, secondary end-point). PET-CT and MRI results before maintenance were also compared with MRD assessed by 8-color flow cytometry. MRI and PET-CT data were analyzed locally in each of the 15 participating centers, and systematically reviewed blindly by an independent committee consisting of 2 radiologists and 2 nuclear medicine physicians with extensive experience in MM field.
Results
At diagnosis, MRI was positive in 127/134 (94.7%), and PET-CT in 122/134 (91%) patients, respectively (McNemar test = 0.94, p-value = 0.33). MRI patterns of marrow involvement were the following: (1) normal in 7 cases (5%); (2) focal lesions (FL) in 46 cases (34%); (3) homogeneous diffuse infiltration in 41 cases (31%); (4) combined diffuse infiltration and FL in 35 cases (26%); and (5) variegated or "salt-and-pepper" pattern with inhomogeneous bone marrow with interposition of fat islands in 5 cases (4%). PET-CT patterns were the following: (1) normal in 12 cases (9%); (2) FL in 44 cases (33%); (3) diffuse infiltration in 12 cases (9%); (4) combined diffuse infiltration and FL in 66 cases (49%); (5) extramedullary disease in 10 cases (7.5%). The median number of FL assessed by PET-CT was 3.
Conclusion
MRI of the spine and pelvis and whole-body PET-CT are equally effective to detect bone involvement in symptomatic patients at diagnosis. The prognosis relevance of both MRI and PET-CT, and the comparison with MRD assessed by flow cytometry will be presented at the meeting.

Disclosures
Karlin: Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Stoppa:Janssen: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Hulin:Celgene Corporation: Honoraria. Marit:Celgene, Janssen: Congress expenses Other.