Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: A multicentre study: European Journal of Cancer

O. Nigro, G. Pinotti, F. De Galitiis, F.R. Di Pietro, R. Giusti, M. Filetti, M. Bersanelli, A. Lazzarin, P. Bordi, A. Catino, P. Pizzutilo, D. Galetta, P. Marchetti, A. Botticelli, S. Scagnoli, M. Russano, D. Santini, M. Torniai, R. Berardi, B. RicciutiA. De Giglio, R. Chiari, A. Russo, V. Adamo, M. Tudini, R.R. Silva, E. Bolzacchini, M. Giordano, P. Di Marino, M. De Tursi, E. Rijavec, M. Ghidini, I. Vallini, L.S. Stucci, M. Tucci, L. Pala, F. Conforti, P. Queirolo, E. Tanda, F. Spagnolo, F. Cecchi, S. Bracarda, S. Macrini, M. Santoni, N. Battelli, M.C. Fargnoli, G. Porzio, A. Tuzi, M.B. Suter, C. Ficorella, A. Cortellini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Data on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICIs) are lacking. Methods: We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in patients with advanced cancer. IrAEs were categorized into ‘early’ (≤12 months) and ‘late’ (>12 months). Results: From September 2013 to October 2019, 436 consecutive patients were evaluated. Two hundred twenty-three experienced any grade early-irAEs (51.1%), whereas 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, whereas 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced GIII/GIV irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95% confidence interval [CI]: 2.8–4.2), whereas the median time to onset of late-irAEs was 16.6 months (95% CI: 15.8–17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (hazard ratio [HR] = 0.63 [95% CI: 0.30–1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95% CI: 0.37–1.56], p = 0.452). In addition, the time-adjusted cumulative risk of death in accordance with both early-irAEs (HR = 0.79 [95% CI: 0.34–1.86], p = 0.598) and late-irAEs (HR = 0.92 [95% CI: 0.49–1.74], p = 0.811) did not show statistically significant differences. Conclusion: Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs. © 2020 Elsevier Ltd
Original languageEnglish
Pages (from-to)19-28
Number of pages10
JournalEur. J. Cancer
Volume134
DOIs
Publication statusPublished - 2020

Keywords

  • Atezolizumab
  • Immune checkpoint
  • Immune-related adverse events
  • Immunotherapy
  • Nivolumab
  • Pembrolizumab
  • atezolizumab
  • corticosteroid
  • nivolumab
  • pembrolizumab
  • programmed death 1 ligand 1
  • immunological antineoplastic agent
  • adult
  • advanced cancer
  • aged
  • Article
  • cancer immunotherapy
  • cancer recurrence
  • clinical outcome
  • death
  • disease exacerbation
  • drug withdrawal
  • endocrine disease
  • female
  • follow up
  • gastrointestinal symptom
  • human
  • liver disease
  • lung disease
  • major clinical study
  • male
  • melanoma
  • neurologic disease
  • non small cell lung cancer
  • observational study
  • priority journal
  • retrospective study
  • rheumatic disease
  • side effect
  • skin disease
  • treatment duration
  • adverse drug reaction
  • adverse event
  • clinical trial
  • immunology
  • immunotherapy
  • middle aged
  • multicenter study
  • neoplasm
  • pathology
  • prognosis
  • survival rate
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasms
  • Prognosis
  • Retrospective Studies
  • Survival Rate

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