Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome.

Lakomy, Tim; Akhoundova, Dilara; Nilius, Henning; Kronig, Marie-Noëlle; Novak, Urban; Daskalakis, Michael; Bacher, Ulrike; Pabst, Thomas (2023). Early Use of Corticosteroids following CAR T-Cell Therapy Correlates with Reduced Risk of High-Grade CRS without Negative Impact on Neurotoxicity or Treatment Outcome. Biomolecules, 13(2) MDPI 10.3390/biom13020382

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BACKGROUND

Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is associated with potentially life-threatening toxicities, most commonly cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS). These frequent adverse events are managed with the IL-6 receptor antagonist tocilizumab and/or corticosteroids. The prophylactic and early use of corticosteroids for CRS and ICANS have previously been reported, but eventual negative impacts on CAR T-cell efficacy are feared.

METHODS

Retrospective comparative analysis of two patient cohorts with hematological malignancies treated with CAR T-cell therapy: 43 patients received early administration of 10 mg dexamethasone preceding each dose of tocilizumab ("early corticosteroid/ tocilizumab", EcsTcz cohort) vs. 40 patients who received tocilizumab alone ("tocilizumab alone", Tcz cohort) for treatment of low-grade CRS.

RESULTS

Despite overall higher CRS incidence (91% vs. 70%; p = 0.0249), no high-grade CRS was observed (0% vs. 10%; p = 0.0497) among patients receiving early corticosteroids in combination with tocilizumab. In terms of neurotoxicity, no worsening regarding incidence of ICANS (30% vs. 33%; p = 0.8177) or high-grade ICANS (20% vs. 14%; p = 0.5624) was observed in the EcsTcz cohort. Moreover, overall response rates (80% vs. 77%; p = 0.7936), complete response rates (50% vs. 44%; p = 0.6628), progression-free survival (p = 0.6345) and overall survival (p = 0.1215) were comparable for both cohorts.

CONCLUSIONS

Our study suggests that the early use of corticosteroids in combination with the standard tocilizumab schedule for low-grade CRS following CAR T-cell therapy may significantly reduce the risk of high-grade CRS without negative impact on neurotoxicity or treatment outcome.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Akhoundova Sanoyan, Dilara, Nilius, Henning Jürgen Jean, Kronig, Marie-Noëlle, Novak, Urban, Daskalakis, Michael, Bacher, Vera Ulrike, Pabst, Thomas Niklaus

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2218-273X

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

02 Mar 2023 15:34

Last Modified:

02 Mar 2023 23:37

Publisher DOI:

10.3390/biom13020382

PubMed ID:

36830750

Uncontrolled Keywords:

CAR T-cell therapy CRS ICANS adverse events corticosteroids neurotoxicity tocilizumab

BORIS DOI:

10.48350/179263

URI:

https://boris.unibe.ch/id/eprint/179263

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