Page 106 - Haematologica Vol. 107 - September 2022

ARTICLE - Body composition impacts CRS after CAR-T therapy D.M. Cordas dos Santos et al.
tem were performed under stringent physiologic con- ditions or in the context of aging,55 which may be negli- gible in the context of adoptive immunotherapies like CAR-T. Third, sarcopenia arises from a dysbalance in obes- ity-associated pro-inflammatory effects leading to muscle catabolism, as well as skeletal muscle-derived anti-in- flammatory signaling resulting in muscle anabolism.30 The pro-inflammatory effects of adipose tissue and concomi- tant metaflammation may outweigh the influence of skel- etal muscle on immune reactions.
Limitations of this study include its retrospective and single-center design with a limited sample size. Addi- tionally, only a small subset of the cohort was obese, making it difficult to generalize assumptions on obesity as a risk factor for CRS. Importantly, the results of the present study need to be validated in larger patient co- horts across multiple health care systems and institu- tions. This may lead to the development of a BC-based risk score for CRS in patients receiving CD19 CAR-T. More- over, we have described optimal discriminatory thresholds for BC parameters, which may be integrated into existing risk models of CAR-T related immunotoxicity to improve diagnostic accuracy and predictive capacity.7,11,47,56 Such en- hanced risk models can form the basis of interventional studies exploring how CAR-T toxicity and efficacy are im- pacted by early and/or prophylactic anti-cytokine ther- apies (e.g., tocilizumab, anakinra) or corticosteroids. Finally, further mechanistic exploration of (CAR) T-cell ex- pansion and distribution of immune cell phenotpyes in the context of elevated BMI or VAT appears warranted.
Still, these initial data provide evidence that BC and adi- pose tissue distribution matter in patients receiving T-cell based immune therapies. The finding that patients with an elevated BMI develop earlier and more severe CRS in- vites future translational research, and underlines how metainflammation may serve as a potentiating force in systemic inflammatory disorders.
Disclosures
KR has received research funding from Kite/Gilead. VB has received research funding from Kite/Gilead, BMS/Celgene and Janssen and consulted for Kite/Gilead and Novartis. VLB received research funding from BMS/Celgene, Miltenyi and Novartis; received honoraria and travel support from Amgen, Kite/Gilead, Novartis and Pfizer; consulted for Kite/Gilead, BMS/Celgene, Novartis and Pfizer; was part of speakers bureau for Novartis and Pfizer. CS work was funded by Bayer and Kite/Gilead; has received honoraria
References
1. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia.
and travel costs from BMS, Janssen, Kite/Gilead, Novartis and consulted for BMS, Kite/Gilead, Novartis and Takeda. MB received honoraria, was part of the speakers bureau of and consulted for MSD Sharpe & Dohme, Novartis, Roche, Kite/Gilead, BMS/Celgene, Astellas, Mologen and Miltenyi. ST received honoraria from and consulted for Amgen, BMS/Celgene, GSK, Janssen, Pfizer, Sanofi and Takeda. MS received honoraria, was part of speakers bureau and was funded by Amgen, BMS/Celgene, Gilead, Novartis; she further received funding from Miltenyi, MorphoSys, Roche; she received honoraria and research funding from Seattle Genetics, honoraria from Janssen and Pfizer and was part of speakers bureau for Pfizer and Takeda. All other authors have no conflicts of interest to disclose.
Contributions
DMCDS, KR, ST and MS designed the study and developed the concept; DMCDS, KR, MW, LL, PT, SG, VLB, VB, CS, WGK, MBB, ST, and MS carried out the research; DMCDS, KR, ST and MS performed the formal analysis and visualized the study; DMCDS, KR and LL developed the methodology; DMCDS, KR, ST and MS wrote the original draft; DMCDS, KR, MW, LL, VLB, VB, CS, WGK, MBB, ST and MS revised and edited the manuscript. All authors read and approved the final manuscript.
Acknowledgments
We are grateful for the support of all patients and the per- sonnel of the LMU University Hospital who supported this work. Figure 1 and 5 were created with BioRender.com.
Funding
DMCDS, KR, VB received a fellowship from the School of Oncology of the German Cancer Consortium (DKTK). DMCDS received funding from Medical Faculty of Ludwig- Maximilians-University in Munich, Germany (FöFoLe Reg.- Nr. 1089). KR, VB and VLB were funded by the Else Kröner Forschungskolleg. LL received funding from the China Scholarship Council (grant no. 201908080031). PT and SG received a doctoral scholarship from Medical Faculty of Ludwig-Maximilians-University in Munich, Germany. This work was partly supported by the Deutsche Forschungs- gemeinschaft (DFG, German Research Foundation, SFB- TRR 338/1 2021-452881907 to ST and MS).
Data-sharing statement
For original data and material, please contact the cor- responding authors.
N Engl J Med. 2018;378(5):439-448.
2. Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and
Haematologica | 107 September 2022
2105