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Review
. 2021 Dec 14;5(23):5312-5322.
doi: 10.1182/bloodadvances.2021004896.

Infectious complications of CAR T-cell therapy across novel antigen targets in the first 30 days

Lekha Mikkilineni  1 , Bonnie Yates  2 , Seth M Steinberg  3 , Shilpa A Shahani  2 , John C Molina  2 , Tara Palmore  4 , Daniel W Lee  2   5 , Rosandra N Kaplan  2 , Crystal L Mackall  2   6 , Terry J Fry  2   7 , Juan Gea-Banacloche  8 , Theresa Jerussi  9 , Veronique Nussenblatt  4 , James N Kochenderfer  1 , Nirali N Shah  2
Affiliations
Review

Infectious complications of CAR T-cell therapy across novel antigen targets in the first 30 days

Lekha Mikkilineni et al. Blood Adv. .

Abstract

Infections are a known complication of chimeric antigen receptor (CAR) T-cell therapy with data largely emerging from CD19 CAR T-cell targeting. As CAR T-cell therapy continues to evolve, infection risks and management thereof will become increasingly important to optimize outcomes across the spectrum of antigens and disease targeted. We retrospectively characterized infectious complications occurring in 162 children and adults treated among 5 phase 1 CAR T-cell clinical trials. Trials included targeting of CD19, CD22, disialoganglioside (GD2) or B-cell maturation antigen (BCMA). Fifty-three patients (32.7%) had 76 infections between lymphocyte depleting (LD) chemotherapy and day 30 (D30); with the majority of infections (61, 80.3%) occurring between day 0 (D0) and D30. By trial, the highest proportion of infections was seen with CD22 CAR T cells (n = 23/53; 43.4%), followed by BCMA CAR T cells (n = 9/24; 37.5%). By disease, patients with multiple myeloma had the highest proportion of infections (9/24; 37.5%) followed by acute lymphoblastic leukemia (36/102; 35.3%). Grade 4 infections were rare (n = 4; 2.5%). Between D0 and D30, bacteremia and bacterial site infections were the most common infection type. In univariate analysis, increasing prior lines of therapy, recent infection within 100 days of LD chemotherapy, corticosteroid or tocilizumab use, and fever and neutropenia were associated with a higher risk of infection. In a multivariable analysis, only prior lines of therapy and recent infection were associated with higher risk of infection. In conclusion, we provide a broad overview of infection risk within the first 30 days post infusion across a host of multiple targets and diseases, elucidating both unique characteristics and commonalities highlighting aspects important to improving patient outcomes.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Incidence and frequency of infections across trial and disease cohorts. (A) Percent of patients with and without infections by protocol between LD and D30. (B) Percent of patients with and without infections by disease type between LD and D30. (C) Percent of infections before and after D0 by protocol. (D) Percent of infections occurring before and after D0 by disease type.
Figure 2.
Figure 2.
Incidence and frequency of infections by time point and across trials. (A) Infection subtype between LD and <D0. (B) Infection subtype by protocol between LD and < D0. (C) Infection subtype between D0 and D30. (D) Infection subtype by protocol between D0 to D30.
Figure 3.
Figure 3.
Cumulative incidence curves for bacteremias, bacterial-site infections, C. diff infections, and viral infections.
Figure 4.
Figure 4.
Patient and treatment characteristics associated with infection between D0 to D30.
See this image and copyright information in PMC

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