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Clinical Trial
. 2025 Feb 11;9(3):571-582.
doi: 10.1182/bloodadvances.2024014360.

Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma

Inés Zugasti  1 , Marta Tormo-Ratera  1 , Aina Oliver-Caldés  1   2 , Juan Carlos Soler-Perromat  1 , Verónica González-Calle  3 , David F Moreno  1 , Valentín Cabañas  4 , Nieves López-Muñoz  5 , Álvaro Bartolomé-Solanas  1 , Marta Español-Rego  1 , Juan Luis Reguera-Ortega  6 , Laura Rosiñol  1 , Lucía López-Corral  3 , Natalia Tovar  1 , Luis Gerardo Rodríguez-Lobato  1 , Rosa Maria Alvarez Perez  6 , Sara Varea  1 , Eulàlia Olesti  1 , Adolfo Gomez-Grande  5 , Laura Frutos  4 , Pilar Tamayo  3 , Manel Juan  1 , José M Moraleda  4 , Álvaro Urbano-Ispizua  1 , E Azucena González-Navarro  1 , Joaquín Martínez-López  5 , Maria-Victoria Mateos  3 , Xavier Tomás  1 , Xavier Setoain  1   7 , Carlos Fernández de Larrea  1
Affiliations
Clinical Trial

Clinical impact of [18F]FDG-PET/CT in ARI0002h treatment, a CAR-T against BCMA for relapsed/refractory multiple myeloma

Inés Zugasti et al. Blood Adv. .

Abstract

Multiple myeloma (MM) remains incurable, with poor outcomes in heavily pretreated patients. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment; however, outcomes after such therapy in patients with soft-tissue plasmacytomas and other bone lesions remain poorly understood. This study included 63 patients with relapsed/refractory MM treated either in the CARTBCMA-HCB-01 clinical trial (ARI0002h; academic B-cell maturation antigen [BCMA]-targeted CAR T-cell therapy) or in compassionate use. The aim was to evaluate the impact of soft-tissue involvement (extramedullary [EMD] and paraskeletal [PS] plasmacytomas) in response, survival and safety. Baseline [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) from 5 participating centers were reviewed centrally. Of 63 patients, 52.4% presented plasmacytomas at the time of inclusion (21 PS, exclusively; and 12 EMD). Per responses, there were no significant differences between patients with and without plasmacytomas. A correlation was present between International Myeloma Working Group responses and those obtained by [18F]FDG-PET/CT at day 100 (Bologna criteria). No differences were observed in progression-free survival (PFS) or overall survival (OS) between patients with or without plasmacytomas. However, both PFS and OS were significantly shorter in patients with EMD. Interestingly, [18F]FDG-PET/CT response assessed on day 100, in accordance with the Bologna criteria, was predictive of survival outcomes. A metabolic tumor volume of ≥25 cm3 at baseline [18F]FDG-PET/CT was associated with earlier disease progression and shorter OS. These results highlight the importance of EMD evaluation by [18F]FDG-PET/CT before and after CAR T-cell infusion. This trial was registered at www.ClinicalTrials.gov as #NCT04309981; and EudraCT, 2019-001472-11.

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Conflict of interest statement

Conflict-of-interest disclosure: A.O.-C. declares nonfinancial support from Janssen, outside from the submitted work. V.C. received honoraria for lectures, consulting, and advisory boards from Johnson&Johnson, Bristol Myers Squibb, Sanofi, Amgen, Glaxo, Pfizer, BioGene, and Menarini; and received travel grants from Johnson&Johnson, Bristol Myers Squibb, Amgen, and BioGene; served on a speakers bureau for Bristol Myers Squibb; and reports financing of scientific research from Janssen. L.G.R.-L. declares honoraria and travel grants from Janssen, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Menarini, and Sanofi. C.F.L. declares receiving grants through his institution from Bristol Myers Squibb, Janssen, and Amgen; reports honoraria from Amgen, Janssen, Bristol Myers Squibb, GlaxoSmithKline, and Sanofi; reports support for attending meetings or travel from Janssen, Bristol Myers Squibb, GlaxoSmithKline, and Amgen; and reports participation on advisory boards with Janssen, Bristol Myers Squibb, Amgen, Pfizer, and Sanofi. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Baseline [18F]FDG-PET/CT of a 55-year-old female patient with IgGκ MM showcasing a multifocal pattern with 6 focal osteolytic lesions with FDG uptake, costal plasmacytoma, and extensive EMD involvement. (A) Maximum intensity projection (MIP). (B-C) [18F]FDG-PET/CT and CT axial cuts of a supraclavicular left lymphadenopathy. (D-E) [18F]FDG-PET/CT and CT axial cuts showing multiple focal liver lesions and a retroperitoneal lymphadenopathy. (F) MIP view with overlay of segmented lesions (MTV = 1031 mL; TLG = 3899 g).
Figure 2.
Figure 2.
Comparison between serological IMWG response and PET/CT response. Description of responses based on IMWG criteria at day 100 (middle column) and PET/CT (right column) at day 100 of ARI0002h infusion based on EMD disease presence (n = 33) or not (n = 30) at screening.
Figure 3.
Figure 3.
Survival curves after ARI0002h infusion. (A-B) PFS and OS of the cohort. (C-D) PFS and OS based on the absence (blue, n = 30) or presence (red, n = 33) of EMD disease. (E-F) PFS and OS based on the absence (blue, n = 30) or presence of PS (pink, n = 21) or EMD (brown, n = 12) plasmacytomas at inclusion.
Figure 4.
Figure 4.
Outcomes according to PET/CT response. PET/CT response at day 100 was predictive of PFS (A) and OS (B). Reaching CMR at PET/CT D100 vs the rest of responses (PMR, NRM, and PD) was associated with a longer survival (C).
Figure 5.
Figure 5.
Biomarkers of disease progressions based on PET/CT values. (A) Univariate and multivariate analysis of TLG, MTV, and SUVmax with the presence of plasmacytomas. All values were considered as continuous, being analyzed for an association with the presence of plasmacytomas. For the multivariate logistic regression model, we included SUVmax, MTV, and TLG values. All 3 values were significant on the univariate model, but only MTV remained significant (P = .033) in the multivariate model. (B) ROC curve showing that MTV of 25 cm3 shows highest sensitivity (90.9%) and specificity (84%) for predicting plasmacytomas presence. All values were considered as continuous, being analyzed for an association with the presence of plasmacytomas. For the multivariate logistic regression model, we included SUVmax, MTV, and TLG values. All 3 values were significant in the univariate model, but only MTV remained significant (P = .033) in the multivariate model. (C) MTV of ≥25 cm3 at baseline PET/CT was associated with higher disease progression (D) and worst OS.
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