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Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy.
Song, Zhiqiang; Tu, Dingyuan; Tang, Gusheng; Liu, Na; Tai, Zongguang; Yang, Jianmin; Wang, Yang.
Afiliação
  • Song Z; Department of Hematology, Institute of Hematology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433.
  • Tu D; Department of Cardiology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200443.
  • Tang G; Department of Hematology, Institute of Hematology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433.
  • Liu N; Department of Hematology, Institute of Hematology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433.
  • Tai Z; Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443. taizongguang@126.com.
  • Yang J; Department of Hematology, Institute of Hematology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433. chyangjianmin@163.com.
  • Wang Y; Department of Hematology, Institute of Hematology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433. yang060124@126.com.
Haematologica ; 108(8): 2067-2079, 2023 08 01.
Article em En | MEDLINE | ID: mdl-36794498
Hematotoxicity is the most common long-term adverse event (AE) after chimeric antigen receptor T-cell (CAR T) therapy. However, patients who receive CAR T therapy in pivotal clinical trials are subjected to restrictive selection criteria, and this means that rare but fatal toxicities are underestimated. Here, we systematically analyzed CAR T-associated hematologic AE using the US Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC); the lower limit of the ROR and IC 95% confidence interval (CI) (ROR025 and IC025) exceeding one and zero was considered significant, respectively. Among the 105,087,611 reports in FAERS, 5,112 CAR T-related hematotoxicity reports were identified. We found 23 significant over-reporting hematologic AE (ROR025 >1) compared to the full database, of which hemophagocytic lymphohistiocytosis (HLH; n=136 [2.7%], ROR025 = 21.06), coagulopathy (n=128 [2.5%], ROR025 = 10.43), bone marrow failure (n=112 [2.2%], ROR025 = 4.88), disseminated intravascular coagulation (DIC; n=99 [1.9%], ROR025 = 9.64), and B-cell aplasia (n=98 [1.9%], ROR025 = 118.16, all IC025 > 0) were highly under-reported AE in clinical trials. Importantly, HLH and DIC led to mortality rates of 69.9% and 59.6%, respectively. Lastly, hematotoxicity-related mortality was 41.43%, and 22 death-related hematologic AE were identified using LASSO regression analysis. These findings could help clinicians in the early detection of those rarely reported but lethal hematologic AE, thus reducing the risk of severe toxicities for CAR T recipients.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Coagulação Intravascular Disseminada / Linfo-Histiocitose Hemofagocítica / Receptores de Antígenos Quiméricos Tipo de estudo: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Humans Idioma: En Revista: Haematologica Ano de publicação: 2023 Tipo de documento: Article País de publicação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Coagulação Intravascular Disseminada / Linfo-Histiocitose Hemofagocítica / Receptores de Antígenos Quiméricos Tipo de estudo: Diagnostic_studies / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Humans Idioma: En Revista: Haematologica Ano de publicação: 2023 Tipo de documento: Article País de publicação: Itália