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1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications

BACKGROUND: CAR T -cell therapy (CTT) is a novel treatment for B-cell cancers. CTT patients (pt) are at risk of infection due to neutropenia, cytokine release syndrome (CRS), and CAR T-cell related encephalopathy syndrome (CRES), which are treated with steroids and tocilizumab (anti-IL-6). This is a...

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Autores principales: Garner, Will, Samanta, Palash, Dorritie, Kathleen, Sehgal, Alison, Winfield, Denise, Agha, Mounzer, Boudreau, Robert, Nguyen, Minh Hong T, Haidar, Ghady
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776724/
http://dx.doi.org/10.1093/ofid/ofaa439.1291
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author Garner, Will
Samanta, Palash
Dorritie, Kathleen
Sehgal, Alison
Winfield, Denise
Agha, Mounzer
Boudreau, Robert
Nguyen, Minh Hong T
Haidar, Ghady
author_facet Garner, Will
Samanta, Palash
Dorritie, Kathleen
Sehgal, Alison
Winfield, Denise
Agha, Mounzer
Boudreau, Robert
Nguyen, Minh Hong T
Haidar, Ghady
author_sort Garner, Will
collection PubMed
description BACKGROUND: CAR T -cell therapy (CTT) is a novel treatment for B-cell cancers. CTT patients (pt) are at risk of infection due to neutropenia, cytokine release syndrome (CRS), and CAR T-cell related encephalopathy syndrome (CRES), which are treated with steroids and tocilizumab (anti-IL-6). This is a single-center study evaluating the risk factors for infection after CTT. METHODS: A retrospective review was conducted of 60 consecutive CTT recipients between 7/17/17 and 9/5/19. Data was collected from 6 months (mo) pre- and at least 6 mo post-CTT. Data was censored for death, additional chemotherapy, or loss to follow up. Cox proportional hazard and Poisson regression were used. RESULTS: Median age was 66 (23-84) years; 48% (29) were female. The most common cancer was non-Hodgkin lymphoma (89%, 54). 25% (15) had a prior stem cell transplant (SCT). 73% (44) and 45% (27) of pts developed CRS and CRES, respectively. 43% (26) received steroids; 65% (39) received tocilizumab. In the 6 mo pre-CTT, 39 infections occurred in 45% (27) of pts. 103 infections occurred in 66% (40) after CTT; 33 (55%) had an infection within 6 mo. Infections were bacterial (52%; 54/103), viral (30%; 37/103), fungal (10%; 10/103), mycobacterial (1%; 1/103), protozoal (1%; 1/103). Cumulative incidence of infection in the first 6 mo are shown in Fig 1. All-cause and infection-related mortality were 32% (19) and 15% (9), respectively. Mortality among pts with fungal infections was 20% (2/10). Infection density was 1.28 and 0.58 infections per 100 pt-days between days 0-30 and 30-89, respectively. Factors associated with infection post CTT were number (no.) of infections in the 6 mo prior to infusion (HR 1.62, CI [1.1-2.38]; p=0.015), no. of lines of therapy in the 6 mo pre-CTT (HR 1.52, CI [1.01-2.27]; p=0.04), prior allogeneic SCT (HR 5.96, CI [1.34-26.47]; p=0.019), and no. of tocilizumab doses. Grade 1 CRS and grade 2 CRES were risk factors between days 0-30 and 0-180, respectively (HR 4.67, CI [1.02 -21.4], p = 0.047; HR 2.48, CI [1.17-5.23], p = 0.02). Fig 1: Cumulative Incidence of Infection 6 Months Post CAR T-cell Therapy [Image: see text] CONCLUSION: Infections after CTT are common. Infection before CTT was associated with risk of infection after CTT. Pt selection may ameliorate this risk. Mortality due to fungal infections was high. Randomized-controlled trials of antifungal prophylaxis in high-risk pts are needed. DISCLOSURES: All Authors: No reported disclosures
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spelling pubmed-77767242021-01-07 1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications Garner, Will Samanta, Palash Dorritie, Kathleen Sehgal, Alison Winfield, Denise Agha, Mounzer Boudreau, Robert Nguyen, Minh Hong T Haidar, Ghady Open Forum Infect Dis Poster Abstracts BACKGROUND: CAR T -cell therapy (CTT) is a novel treatment for B-cell cancers. CTT patients (pt) are at risk of infection due to neutropenia, cytokine release syndrome (CRS), and CAR T-cell related encephalopathy syndrome (CRES), which are treated with steroids and tocilizumab (anti-IL-6). This is a single-center study evaluating the risk factors for infection after CTT. METHODS: A retrospective review was conducted of 60 consecutive CTT recipients between 7/17/17 and 9/5/19. Data was collected from 6 months (mo) pre- and at least 6 mo post-CTT. Data was censored for death, additional chemotherapy, or loss to follow up. Cox proportional hazard and Poisson regression were used. RESULTS: Median age was 66 (23-84) years; 48% (29) were female. The most common cancer was non-Hodgkin lymphoma (89%, 54). 25% (15) had a prior stem cell transplant (SCT). 73% (44) and 45% (27) of pts developed CRS and CRES, respectively. 43% (26) received steroids; 65% (39) received tocilizumab. In the 6 mo pre-CTT, 39 infections occurred in 45% (27) of pts. 103 infections occurred in 66% (40) after CTT; 33 (55%) had an infection within 6 mo. Infections were bacterial (52%; 54/103), viral (30%; 37/103), fungal (10%; 10/103), mycobacterial (1%; 1/103), protozoal (1%; 1/103). Cumulative incidence of infection in the first 6 mo are shown in Fig 1. All-cause and infection-related mortality were 32% (19) and 15% (9), respectively. Mortality among pts with fungal infections was 20% (2/10). Infection density was 1.28 and 0.58 infections per 100 pt-days between days 0-30 and 30-89, respectively. Factors associated with infection post CTT were number (no.) of infections in the 6 mo prior to infusion (HR 1.62, CI [1.1-2.38]; p=0.015), no. of lines of therapy in the 6 mo pre-CTT (HR 1.52, CI [1.01-2.27]; p=0.04), prior allogeneic SCT (HR 5.96, CI [1.34-26.47]; p=0.019), and no. of tocilizumab doses. Grade 1 CRS and grade 2 CRES were risk factors between days 0-30 and 0-180, respectively (HR 4.67, CI [1.02 -21.4], p = 0.047; HR 2.48, CI [1.17-5.23], p = 0.02). Fig 1: Cumulative Incidence of Infection 6 Months Post CAR T-cell Therapy [Image: see text] CONCLUSION: Infections after CTT are common. Infection before CTT was associated with risk of infection after CTT. Pt selection may ameliorate this risk. Mortality due to fungal infections was high. Randomized-controlled trials of antifungal prophylaxis in high-risk pts are needed. DISCLOSURES: All Authors: No reported disclosures Oxford University Press 2020-12-31 /pmc/articles/PMC7776724/ http://dx.doi.org/10.1093/ofid/ofaa439.1291 Text en © The Author 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Poster Abstracts
Garner, Will
Samanta, Palash
Dorritie, Kathleen
Sehgal, Alison
Winfield, Denise
Agha, Mounzer
Boudreau, Robert
Nguyen, Minh Hong T
Haidar, Ghady
1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
title 1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
title_full 1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
title_fullStr 1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
title_full_unstemmed 1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
title_short 1105. The Burden of Infections Prior to Chimeric Antigen Receptor (CAR) Modified T-cell Therapy Predicts Post-CAR T-cell Infectious Complications
title_sort 1105. the burden of infections prior to chimeric antigen receptor (car) modified t-cell therapy predicts post-car t-cell infectious complications
topic Poster Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776724/
http://dx.doi.org/10.1093/ofid/ofaa439.1291
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