Incidence and clinical implications of late immune-related adverse events in long responders to PD-1/PD-L1 checkpoint inhibitors: A multicenter study
| Autor: | A. Russo, Raffaele Giusti, Daniele Santini, A. Lazzarin, Olga Nigro, Domenico Galetta, E. Rijavec, F.R. Di Pietro, P. Pizzutillo, F. De Galitiis, Piero Marchetti, Graziella Pinotti, A. De Giglio, Clara Natoli, Rosa Rita Silva, Ilaria Vallini, E. Bolzacchini, Melissa Bersanelli, Mariangela Torniai, Alessio Cortellini |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Population 03 medical and health sciences 0302 clinical medicine Internal medicine PD-L1 medicine education Adverse effect education.field_of_study biology business.industry Incidence (epidemiology) Retrospective cohort study Hematology Immunotherapy medicine.disease Primary tumor Discontinuation 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein business |
| Zdroj: | Annals of Oncology. 30:xi20 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdz449.009 |
| Popis: | Background Immunotherapy has become a standard of care for an increasing number of tumors. Patients have a chance of developing immune-related adverse events (irAEs). In general, irAEs occur quite early, mostly within weeks to 3 months after initiation of treatment. Being drugs relatively innovative, “late” irAEs are still unknown. Methods We conducted a multicenter retrospective study of advanced cancer patients (any histology, regardless of treatment line) treated with anti-PD-1/PD-L1 (mono)immunotherapy, with a minimum time to treatment failure (TTF) of 12 months. IrAEs were categorized into “early” ( Results We evaluated 318 consecutive patients treated with immunotherapy from September 2013 to August 2018. Median age was 68.6 years (32-90). 175 patients (55.5%) experienced any grade early-irAEs, while 110 (34.6%) experienced any grade late-irAEs (p = 0.0013); 13 patients (4.1%) experienced G3/G4 early-irAEs, while 12 (3.8%) G3/G4 late-irAEs (p = 0.8446). There was a significant association between the occurrence of any grade early-irAEs and late-irAEs (p = 0.0452), as well as between G3/G4 early-irAEs and late-irAEs (p = 0.0251). Among patients who experienced early-irAEs, 63 (36%) experienced “multiple-site” irAEs (multiple sites/organs), while 17 patients (15.4%) experienced multiple-site late-irAEs (p = 0.0040). The median period of follow-up was 22.2 months. The median time to irAEs onset were 3.1 and 16.1 months for early- and late-irAEs, respectively. Late irAEs were not significantly related to TTF; on the other hand, were significantly related to a prolonged OS. When adjusted for primary tumor, late-irAEs were confirmed to be significantly related to a prolonged OS (HR = 0.25 [95%CI:0.11-0.55]; p = 0.0006). Conclusion Late-irAEs among long responders seem to have a mild/moderate incidence. They are mostly non-serious and clinical manageable, with a low rate of treatment discontinuation. In this positive-selected population, the occurrence of any grade late-irAEs seems to be furtherly related to a prolonged OS. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. |
| Databáze: | OpenAIRE |
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