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Predictive value of pre-infusion tumor growth rate for the occurrence and severity of CRS and ICANS in lymphoma under CAR T-cell therapy

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Abstract

Chimeric antigen receptor T-cell therapy (CART) can be administered outpatient yet requires management of potential side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The pre-infusion tumor burden is associated with CRS, yet there is no data on the relevance of pre-infusion tumor growth rate (TGR). Our objective was to investigate TGR for the occurrence and severity of CRS and ICANS. Consecutive patients with available pre-baseline and baseline (BL) imaging before CART were included. TGR was determined as both absolute (abs) and percentage change (%) of Lugano criteria-based tumor burden in relation to days between exams. CRS and ICANS were graded according to ASTCT consensus criteria. Clinical metadata was collected including the international prognostic index (IPI), patient age, ECOG performance status, and LDH. Sixty-two patients were included (median age: 62 years, 40% female). The median pre-BL TGR [abs] and pre-BL TGR [%] was 7.5 mm2/d and 30.9%/d. Pre-BL TGR [abs] and pre-BL TGR [%] displayed a very weak positive correlation with the grade of CRS (r[abs] = 0.14 and r[%] = 0.13) and no correlation with ICANS (r[abs] =  − 0.06 and r[%] =  − 0.07). There was a weak positive correlation between grade of CRS and grade of ICANS (r = 0.35; p = 0.005) whereas there was no significant correlation of CRS or ICANS to any other of the examined parameters. The pre-infusion TGR before CART was weakly associated with the occurrence of CRS, but not the severity, whereas there were no significant differences in the prediction of ICANS. There was no added information when compared to pre-infusion tumor burden alone. Outpatient planning and toxicity management should not be influenced by the pre-infusion TGR.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BL :

Baseline

CART :

Chimeric antigen receptor T-cell therapy

CRS :

Cytokine release syndrome

ECOG :

Eastern Cooperative Oncology Group

FDG :

Fluorodeoxyglucose

FL :

Follicular lymphoma

ICANS :

Immune effector cell-associated neurotoxicity syndrome

IPI :

International prognostic index

IQR :

Interquartile range

LBCL :

Large B-cell lymphoma

LDH :

Lactate dehydrogenase

MCL :

Mantle-cell lymphoma

OS :

Overall survival

PET/CT :

Positron emission tomography-computed tomography

PFS :

Progression-free survival

r/r :

Relapsed or refractory

SPD :

Sum of the product diameters

TB :

Tumor burden

TGR :

Tumor growth rate

TL :

Target lesion

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Funding

The work was supported by funding from the research program “Förderung für Forschung und Lehre (FöFoLe) project number 1147” of the Medical Faculty of Ludwig Maximilian University (LMU) Munich and the Bavarian Cancer Research Center (BZKF) to M.W. The work was further supported by the Else-Kröner-Fresenius Stiftung (to V.B.) and the German Cancer Consortium DKTK (to V.B.).

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Authors and Affiliations

  1. Department of Radiology, University Hospital, LMU Munich, Munich, Germany

    Michael Winkelmann, Christina Quell, Maria Ingenerf, Marcus Unterrainer, Jens Ricke & Wolfgang G. Kunz

  2. Laboratory for Translational Cancer Immunology, Gene Center of the LMU Munich, Munich, Germany

    Viktoria Blumenberg, Kai Rejeski, Veit L. Bücklein & Marion Subklewe

  3. German Cancer Consortium (DKTK) and Bavarian Center for Cancer Research (BZKF), Partner Site Munich, Munich, Germany

    Viktoria Blumenberg, Kai Rejeski, Veit L. Bücklein, Michael von Bergwelt-Baildon, Marion Subklewe & Wolfgang G. Kunz

  4. Department of Medicine III, University Hospital, LMU Munich, Munich, Germany

    Viktoria Blumenberg, Kai Rejeski, Veit L. Bücklein, Christian Schmidt, Michael von Bergwelt-Baildon & Marion Subklewe

  5. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany

    Franziska J. Dekorsy & Peter Bartenstein

  6. Comprehensive Cancer Center München-LMU (CCCM LMU), LMU Munich, Munich, Germany

    Peter Bartenstein, Jens Ricke, Michael von Bergwelt-Baildon, Marion Subklewe & Wolfgang G. Kunz

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  1. Michael Winkelmann
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Contributions

M.W. and W.G.K. conceived and designed the study; V.B., K.R., C.Q., V.L.B., M.I., M.U., and C.S. collected the data; M.W., V.B., K.R., C.Q., V.L.B., and W.G.K. analyzed and interpreted the data; M.W. and W.G.K. drafted the manuscript; and all authors revised the manuscript.

Corresponding author

Correspondence to Wolfgang G. Kunz.

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Ethics approval

All medical records and imaging studies were reviewed with the approval of the LMU Munich Institutional Review Board (LMU Ethics Committee, project number 19–817).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

V.B.: BMS/Celgene: research funding; Kite/Gilead: consultancy, honoraria, research funding; Janssen: research funding, honoraria; Novartis: research funding, honoraria; Roche: consultancy, research funding; Takeda: research funding. K.R.: Kite/Gilead: research funding; Kite/Gilead: travel support; Novartis: honoraria. V.L.B.: Amgen: honoraria; Celgene/BMS: research funding; Kite/Gilead: research funding, honoraria; Novartis: honoraria; Pfizer: honoraria. C.S.: Kite/Gilead: travel support. M.v.B.: Astellas: consultancy, research funding, and honoraria; BMS: consultancy, research funding, and honoraria; Kite/Gilead: consultancy, research funding, and honoraria; Miltenyi: consultancy, research funding, and honoraria; Mologen: consultancy, research funding, and honoraria; MSD Sharp & Dohme: consultancy, research funding, and honoraria; Novartis: consultancy, research funding, and honoraria; Roche: consultancy, research funding, and honoraria. M.S.: Amgen: research funding, speakers bureau; Astra Zeneca: speakers bureau; Aven Cell: consultancy; BMS/Celgene: research funding, speakers bureau; CDR-Life: consultancy; Gilead: research funding, speakers bureau; GSK: speakers bureau; Ichnos Sciences: consultancy; Incyte Biosciences: consultancy; Janssen: research funding, consultancy, speakers bureau; Miltenyi Biotec: research funding, consultancy; Morphosys: research funding; Molecular Partners: consultancy; Novartis: research funding, consultancy, speakers bureau; Pfizer: consultancy, speakers bureau; Roche: research funding, speakers bureau; Seattle Genetics: research funding; Takeda: research funding, consultancy, speakers bureau. W.G.K.: Bristol Myers Squibb: advisor; mint Medical: advisor; Need, Inc: advisor; Boehringer Ingelheim, advisor. The remaining authors declare no competing financial interests. None of the mentioned conflicts of interest were related to financing of the content of this manuscript.

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Winkelmann, M., Blumenberg, V., Rejeski, K. et al. Predictive value of pre-infusion tumor growth rate for the occurrence and severity of CRS and ICANS in lymphoma under CAR T-cell therapy. Ann Hematol 103, 259–268 (2024). https://doi.org/10.1007/s00277-023-05507-9

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