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Prognostic implications of splenomegaly in BCMA-directed CAR T-Cell therapy for relapsed myeloma

Jerina Hoxha

22.7.25

New CERTAINTY-supported publication identifies spleen size as a prognostic marker in CAR T cell treatment

A new study published in Transplantation and Cellular Therapy of ASTCT explores the prognostic role of splenomegaly (enlarged spleen size) in patients receiving BCMA-directed CAR T cell therapy for relapsed or refractory multiple myeloma. The study shows that splenomegaly is associated with higher tumour burden, deeper and prolonged cytopenias, and shorter survival outcomes. The research contributes to the understanding of how imaging-derived parameters can inform treatment risk stratification.


Background

BCMA-directed CAR T cell therapy has emerged as a transformative option for patients with relapsed or refractory multiple myeloma. However, predictive tools to estimate therapy-related toxicity and long-term outcomes are still limited. In this retrospective, single-centre study, 73 patients were analysed to evaluate whether spleen volume, measured by baseline PET/CT imaging prior to CAR T cell therapy infusion, could serve as a predictive biomarker. Two CAR T products were administered: ide-cel in 35 patients and cilta-cel in 38 patients. Various clinical, imaging, and laboratory outcome parameters were subsequently evaluated.


Key findings

  • An enlarged spleen prior to CAR T cell therapy is associated with:

    • Higher metabolic tumour volume

    • Higher serum BCMA (sBCMA) levels

    • More severe and prolonged thrombocytopenia

  • Spleen size shows independent prognostic value for progression-free survival and overall survival.

  • Splenomegaly prior to CAR T Cell infusion predicts treatment response and survival.

  • Splenomegaly impairs CAR T cell Expansion.


Conclusions

This study positions spleen size as a meaningful biomarker for both disease burden and treatment-related toxicity in BCMA-directed CAR T cell therapy. Importantly, spleen volume can be derived from standard-of-care PET/CT imaging, offering a practical addition to pre-treatment assessments.


The results underscore the value of multimodal clinical data integration, including imaging, biomarkers, and outcomes, in personalising cancer therapy, directly supporting the approach being developed within CERTAINTY's virtual twin.


Access the publication

Read the full open-access publication in Transplantation and Cellular Therapy: https://doi.org/10.1016/j.jtct.2025.07.003

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Funded by the European Union Logo

This project was funded by the European Union under Grant Agreement number 101136379. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them.

© 2025 by Collaborate Project Management GmbH.

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