ORIGINAL RESEARCH article
Front. Hematol.
Sec. Gene Therapy, Cell Therapy and Hematology
Volume 4 - 2025 | doi: 10.3389/frhem.2025.1618331
Pre-infusion ferritin a predictive biomarker for CAR T-cell therapy in R/R multiple myeloma
Provisionally accepted
Eider Moreno-Cortes
Mariano Arribas
David Martinez
Juana C Figueroa Aguirre
Rohan Patel
Daniel T BihnamUdit YadavErin Wiedmeier-NutorLeif Bergsagel
Saurabh ChhabraRafael Fonseca
Januario E. Castro, M.D.*- Mayo Clinic Arizona, Scottsdale, United States
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Evaluating predictive biomarkers early in treatment, clinicians can anticipate patient responses and tailor therapeutic strategies to enhance efficacy and survival outcomes. Ferritin has emerged as a promising predictor of clinical outcomes in multiple myeloma (MM) patients undergoing chimeric antigen receptor (CAR) T-cell therapy. In this study, we investigated the prognostic value of ferritin and C-reactive protein (CRP) as biomarkers in CAR T-cell therapy for MM. This study's objective was to evaluate the correlation between ferritin and CRP levels at two time points pre-infusion (Day-0) and pre-lymphodepleting chemotherapy (LDC) and their association with clinical response outcomes. We retrospectively analyzed outcomes from 52 relapsed/refractory MM (RRMM) patients who received either idecabtagene vicleucel or ciltacabtagene autoleucel CAR T-cell therapies. Low ferritin levels at Day-0 and pre-LDC were able to predict better responses regardless of the CAR T cell product (hazard ratio [HR] 0.01 (95% CI 0.05-0.5); p=0.001, (HR 0.05 95% CI 0.01-0.2, p=<0.0069), respectively. Low ferritin + low CRP were able to predict responses at Day-0 and pre-LDC HR 0.3 (95% CI 0.07-1.3); p=0.04, HR 0.26 (95% CI 0.03-2.1), p=0.04, respectively. Our results indicate that ferritin and CRP levels represent promising predictive biomarkers that may refine CAR T-cell therapy response by enabling better patient stratification and personalized treatment approaches. Our study underscores the need for their integration into routine clinical practice for MM management. Future prospective studies are warranted to validate these findings and explore the mechanistic link between elevated ferritin levels, immune activation states, and CAR T-cell efficacy.
Keywords: CAR T cell, Multiple Myeloma, ferritin, C reactive protein (CRP), ciltacabtagene autoleucel, Idecabtagene vicleucel
Received: 25 Apr 2025; Accepted: 10 Jul 2025.
Copyright: © 2025 Moreno-Cortes, Arribas, Martinez, Figueroa Aguirre, Patel, Bihnam, Yadav, Wiedmeier-Nutor, Bergsagel, Chhabra, Fonseca and Castro, M.D.. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Januario E. Castro, M.D., Mayo Clinic Arizona, Scottsdale, United States
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