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Observational Study
. 2024 Aug 22;12(8):e009728.
doi: 10.1136/jitc-2024-009728.

Safety and tolerability of immune checkpoint inhibitors in people with HIV infection and cancer: insights from the national prospective real-world OncoVIHAC ANRS CO24 cohort study

Affiliations
Observational Study

Safety and tolerability of immune checkpoint inhibitors in people with HIV infection and cancer: insights from the national prospective real-world OncoVIHAC ANRS CO24 cohort study

Lambert Assoumou et al. J Immunother Cancer. .

Abstract

Background: Immune checkpoint inhibitors (ICIs) have been a major advance in cancer management. However, we still lack prospective real-world data regarding their usage in people with HIV infection (PWH).

Methods: The ANRS CO24 OncoVIHAC study (NCT03354936) is an ongoing prospective observational cohort study in France of PWH with cancer treated with ICI. We assessed the incidence of grade ≥3 immune-related adverse events (irAEs). All grade ≥3 irAEs were reviewed by an event review.

Results: Between January 17, 2018, and December 05, 2023, 150 participants were recruited from 33 sites and 140 were included in this analysis. At the data cut-off date of December 05, 2023, the median follow-up was 9.2 months (IQR: 3.9-18.3), with a total of 126.2 person-years.Median age was 59 years (IQR: 54-64) and 111 (79.3%) were men. Median time since HIV diagnosis was 25 years (12-31), the median duration on antiretroviral (ARV) was 19.5 years (7.7-25.4), and the CD4 nadir was 117/µL (51-240). ICI regimens comprised anti-programmed cell death protein-1 (PD-1) for 111 (79.3%) participants, anti-programmed death-ligand 1 for 25 (17.9%), a combination of anti-PD-1 and anti-cytotoxic T-lymphocyte associated protein 4 for 3 (2.1%), and anti-PD-1 along with anti-vascular endothelial growth factor receptor for 1 (0.7%). The most frequent cancers were lung (n=65), head/neck (n=15), melanoma (n=12), liver (n=11) and Hodgkin's lymphoma (n=9).During follow-up, a total of 34 grade ≥3 irAEs occurred in 20 participants, leading to an incidence rate of 26.9 per 100 person-years. The Kaplan-Meier estimates of the proportion of participants with at least one episode of grade ≥3 irAEs were 13.8% at 6 months, 15.0% at 12 months and 18.7% at 18 months. One treatment-related death due to myocarditis was reported (0.7%). Multivariable analysis of cumulative incidence showed that participants with time since HIV diagnosis >17 years (incidence rate ratio (IRR)=4.66, p=0.002), with CD4<200 cells/µL (IRR=4.39, p<0.0001), with positive cytomegalovirus (CMV) serology (IRR=2.76, p=0.034), with history of cancer surgery (IRR=3.44, p=0.001) had a higher risk of incidence of grade ≥3 irAEs.

Conclusion: This study showed that the incidence of a first episode of grade ≥3 irAE was 15.0% (95% CI: 9.6% to 22.9%) at 1 year and the cumulative incidence of all severe irAE episodes was 26.9 per 100 person-years. Low CD4 count, positive CMV serology, history of cancer surgery and a longer time since HIV diagnosis were associated with the occurrence of severe irAEs.

Keywords: Immune Checkpoint Inhibitors; Immune related adverse event - irAE; Immunocompromised; Immunotherapy; Infection.

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Conflict of interest statement

Competing interests: DC received personal fees from Pfizer for a lecture outside of the submitted work. A-GM and CK received consulting fees from Gilead Sciences, Merck, and ViiV. J-PS received grant from MSD avenir and personal fees from Roche, MSD, AZ, Novartis, leopharma, PFO, Lilly, Gilead, Daichy-sakyo, and Pfizer for lectures, presentations, speakers bureaus, manuscript writing or educational events outside of the submitted work. OL reports paid expert testimony and consultancy fees from BMS France, MSD; consultancy fees from Boehringer, AbbVie. BA reports research grant from MSD avenir, and consulting fees or honoraria from Novartis, AstraZeneca, BMS, MSD, Astellas, and Sanofi. MV received consulting fees from Gilead Sciences. All other authors declare no competing interests.

Figures

Figure 1
Figure 1. Flowchart of the study. AE, adverse event; e-CRF, electronic case report form; SAE, serious adverse event.
Figure 2
Figure 2. Number of immune checkpoint inhibitors (ICI) received by cancer-type. CEMI, Squamous cell carcinoma.
Figure 3
Figure 3. Kaplan-Meier estimates of the probability of survival according to CD4 nadir (A); CD4 count at baseline (B); CD4:CD8 ratio at baseline (C); immune checkpoint inhibitor (ICI) type (D); cancer type (E) and inclusion period (F).

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