Prognostic Value of Positron Emission Tomography/Computed Tomography in Multiple Myeloma Patients Treated with Ide-Cel CAR-T Cell Therapy: Preliminary Results of a Real-World IFM Study from the Descar-T Registry (CAR MY PET)

Context:¹⁸F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) has prognostic value for progression-free survival (PFS) and overall survival (OS) in newly diagnosed multiple myeloma (MM). However, the prognostic value of PET/CT in the setting of relapsed/refractory (RR) MM treated with CAR-T cell therapy is unclear. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T-cell therapy, was granted authorization through the early access program (EAP) in France in April 2021 for treatment of RRMM. We conducted a real-world DESCAR-T registry-based multicenter observational study in 10 French hospitals with a centralized review of PET/CT performed before CAR T-cells infusion, and during follow-up.

Materials and methods:

One hundred consecutive patients (pts) with RRMM treated with ide-cel in the EAP with PET/CT before CAR T-cell infusion were included. After infusion, PET/CT was performed at one month (M1), three months (M3), six and 12 months (M6 and M12). For each visit, focal lesion (FL), bone marrow uptake (BM), paramedullary (PMD) and extramedullay (EMD) diseases as well as BM maximum standardized uptake value (SUV Max) were assessed. All PET/CT scans were centrally reviewed and lesions measured according to Deauville criteria during the follow-up with PET/CT negativity (complete response) defined as Deauville score 1-3. Clinico-biological data were collected from the French national DESCAR-T. Initial data for the first 58 pts are presented here.

Progression-free survival (PFS) was defined as the time between CAR T-cell infusion and progression during follow-up. OS was defined as the time between CAR T-cell treatment and death during follow-up. Prognostic value of baseline PET/CT on PFS was assessed, as well as the concordance between PET/CT negativity and response according to IMWG criteria.

Results: The 58 pts (male: 47%), had a median age of 58 years (55-70) and received a median of 5 prior lines of treatment before Ide-cel. Baseline PET/CT was available for 58 pts, 51 and 46 were PET/CT evaluable at M1 and M3, respectively. At baseline, 22% of pts were PET/CT negative (-), 38 % had abnormal (Deauville 4 or 5) BM uptake, 69% had FL, 47% PMD and only 16% EMD. Median PFS was 21 months in pts with PET/CT (-) versus 13.6 months in pts with positive (+) PET/CT. SUVmax had no impact on PFS. Conversely, in patients with PMD at baseline median PFS (8.8 months) was significantly lower than pts without PMD (21 months (HR: 2.42; 95%CI (1.16 - 5.06); P = 0.018). The presence of PMD had also a negative impact on OS at 1 year (p= 0.026). At M1 post Ide-cel, median PFS of pts with PET/CT - was 18 months versus 12.4 months in pts with PET/CT+. At M1 and M3 post Ide-cel, PET/CT was negative in 57% and 61% of patients, respectively. At M1, 59% of patients reached response superior to very good partial response (> VGPR). Pts with response < VGPR and PET/CT(+) at M1 had a significantly lower PFS (median 5.5 months) than pts with < VGPR and PET/CT(-) (median 18.3 months) (HR: 3.79; 95%CI (1.28 - 11.23); p= 0.016). At M3, 16 patients with response > VGPR were PET/CT (-), but the overall concordance between PET/CT and hematological response was low (K = 0.04 [95%CI: -0.26; 0.34] (p=0.41]).

Conclusion: This study highlights that baseline PET/CT, especially in pts with PMD, has a prognostic value for PFS in RRMM patients treated with Ide-cel. At 1months, pts with PET/CT+ and <VGPR had very poor prognosis with median PFS less than 6 months. The low concordance between PET/CT and hematological response may provide insight into using both PET/CT and more sensitive methods including MRD as prognostic markers for patient outcomes. Data with more pts and follow up will be presented during the meeting.

Arnulf:BMS, janssen, amgen, Sanofi: Consultancy, Honoraria. Vercellino:Kite Pharma: Consultancy; Genmab: Consultancy; MSD: Other: hospitality; Siemens Healthcare: Other: hospitality; Sanofi Aventis: Other: hospitality. Perrot:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Menarini Stemline: Honoraria; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Abbvie: Honoraria. Vincent:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Financing access to congress; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Financing access to congress; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Financing access to congress; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Financing access to congress; Pfizer: Other: Financing access to congress. Stephanie:Janssen, Sanofi, BMS, PFIZER: Consultancy, Honoraria. Mohty:Stemline Menarini: Honoraria; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria; BMS: Consultancy, Honoraria; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria; GSK: Honoraria; Adaptive: Honoraria; MaaT Pharma: Current equity holder in publicly-traded company. Manier:Adaptive Biotechnology: Consultancy; Abbvie: Consultancy; Celgene/BMS: Consultancy; Amgen: Consultancy; GlaxoSmithKline: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Regeneron: Consultancy; Roche: Consultancy; Sanofi: Consultancy; Takeda: Consultancy. Yakoub-Agha:Miltenyi Biomedicine: Honoraria; Novartis: Honoraria; KITE: Honoraria; BMS: Honoraria. Talbot:BMS, Janssen, Amgen, Sanofi: Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Consultancy; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Honoraria; Celgene, Janssen, Takeda, Amgen, Pfizer, AbbVie, Sanofi: Other: Participation on a Data Safety Monitoring Board or advisory board .