title: Anti-programmed cell death protein 1 tolerance and efficacy after ipilimumab immunotherapy: observational study of 39 patients.
abstract: In patients with ipilimumab (IPI)-refractory melanoma, the anti-programmed cell death proteins 1 (PD1s) nivolumab (NIV) and pembrolizumab (PEM) are considered to be a new standard of treatment. Few data are available on anti-PD1 safety in patients who develop IPI-related severe adverse events (AEs) (grade≥3). The aim of this study was to compare the anti-PD1 safety and efficacy in patients with previous severe toxicity to IPI versus in those showing moderate and no previous IPI-related AEs. This single institution-based observational study included all patients treated with anti-PD1 (PEM or NIV) and previously treated with IPI for unresectable stage III or IV melanoma. The patients enrolled were classified according to the occurrence of IPI-related AEs: group A: no previous IPI-related AEs; group B: mild to moderate IPI-related AEs; and group C: severe to life-threatening IPI-related AEs. The main outcome measure was safety of the anti-PD1 among the three groups. The secondary endpoints included response parameters. Groups A, B, and C included, respectively, 16, 13, and 10 patients. The incidence of severe anti-PD1-related AEs (grades 3-4) was 12, 23, and 10% in groups A, B, and C, respectively. One-year estimates of survival were 52.2, 73.4, and 66.7% among the patients in groups A, B, and C, respectively. The number of patients was too small to enable a meaningful statistical comparison. We did not observe any difference in anti-PD1 toxicity onset incidence according to the occurrence of previous IPI AEs. These reassuring real-life data should be confirmed in a wider analysis.
authors.affiliation: aDepartment of Dermatology, Saint-Louis Hospital bMelBase, Assistance publique hôpitaux de Paris cCRESS UMR 1153, Centre de recherche épidémiologie et statistique Sorbonne Paris cité, Paris, France.
authors.forename: Reyhan
authors.initials: R
authors.lastname: Amode
authors.forename: Barouyr
authors.initials: B
authors.lastname: Baroudjian
authors.forename: Anita
authors.initials: A
authors.lastname: Kowal
authors.forename: Majdi
authors.initials: M
authors.lastname: Jebali
authors.forename: Clara
authors.initials: C
authors.lastname: Allayous
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Nika
authors.initials: N
authors.lastname: Madjlessi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roux
authors.forename: Manuelle
authors.initials: M
authors.lastname: Viguier
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset Seguin
authors.forename: Raphaël
authors.initials: R
authors.lastname: Porcher
authors.forename: Cécile
authors.initials: C
authors.lastname: Pagès
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbé
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab / Q000009:adverse effects*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D019233:Retreatment; D015996:Survival Rate
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab; C582435:pembrolizumab