Prevalence of immune-related adverse events and anti-tumor efficacy following immune checkpoint inhibitor therapy in Japanese patients with various solid tumors

• Published in: BMC cancer 2022-11, Vol.22 (1), p.1232-9, Article 1232
• Main Authors: Yoshikawa, Yuki, Imamura, Michio, Yamauchi, Masami, Hayes, C Nelson, Aikata, Hiroshi, Okamoto, Wataru, Miyata, Yoshihiro, Okada, Morihito, Hattori, Noboru, Sugiyama, Kazuhiko, Yoshioka, Yukio, Toratani, Shigeaki, Takechi, Masaaki, Ichinohe, Tatsuo, Ueda, Tsutomu, Takeno, Sachio, Kobayashi, Tsuyoshi, Ohdan, Hideki, Teishima, Jun, Hide, Michihiro, Nagata, Yasushi, Kudo, Yoshiki, Iida, Koji, Chayama, Kazuaki
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Cancer; Care and treatment; Clinical outcomes; Combination therapy; Complications and side effects; CTLA-4 protein; Cytotoxic T-lymphocyte antigen 4; Cytotoxicity; Diabetes; Disease; Disease control; Enzyme inhibitors; Evaluation; Health risk assessment; Humans; Hypothyroidism; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune-related adverse events; Immune-related liver injury; Immunotherapy; Inflammatory bowel disease; Japan - epidemiology; Laboratories; Leukocytes (eosinophilic); Liver; Lymphocytes T; Malignancy; Medical records; Melanoma; Multivariate analysis; Neoplasms - drug therapy; Patients; PD-1 protein; PD-L1 protein; Pneumonia; Prevalence; Programmed death 1; Retrospective Studies; Risk factors; Solid tumors; Statistical analysis; Terminology; Tumors
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-10327-7

While immune checkpoint inhibitors (ICIs) occasionally cause immune-related adverse events (irAEs) in various organs, the prevalence of irAEs and potential risk factors have not been clarified. We identified irAE predictive factors and examined the relationship between the effect of ICIs and irAEs for patients with malignancies. A total of 533 cases treated with ICIs, including programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), for various malignancies were included retrospectively. We recorded irAEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 5. Prevalence and predictive factors associated with immune-related liver injury and the relationship between irAE and treatment response were analyzed. During a median of 10 (1-103) cycles with a median follow-up after several ICI initiations of 384 (21-1715) days, irAEs with all grades and with grade ≥ 3 developed in 144 (27.0%) and 57 (10.7%) cases. Cumulative irAE development rates were 21.9, 33.5, and 43.0% in all grades and 8.8, 14.9, and 20.7% in grade ≥ 3 at 5, 10, and 20 cycles, respectively. Patients who received anti-CTLA4 therapy were more likely to develop irAEs compared to those who received anti-PD-1 or anti-PD-L1 monotherapy. Liver injury was the most common irAE. Multivariate analysis identified the combination of PD-1 and anti-CTL-4 antibodies (hazard ratio [HR], 17.04; P