Artsen moeten op hun hoede zijn voor immuungerelateerde ernstige bijwerkingen (irAE's), zelfs nadat kankerpatiënten (in deze studie ging het om melanoompatiënten) al een jaar of langer immuuntherapie hebben gehad met anti-PD-1 medicijnen (checkpoint remmers) en daar mee waren gestopt.
Onderzoekers publiceerden eind maart 2021 in Annals of oncology een studierapport dat bij 5,3 procent van de melanoompatiënten die immuuntherapie met anti-PD medicijnen hadden gehad voor hun ziekte nieuwe ernstige bijwerkingen ontstonden na zelfs 1 jaar of langer nadat de anti-PD-1-behandeling had plaatsgevonden.
In een reviewstudie met deelname van 118 patiënten met een melanoom ontdekten ze dat irAE's vaak 'hooggradig waren, moeilijk te behandelen en soms zelfs tot overlijden kunnen leiden, aldus de onderzoekers.
De kans is groter dat deze ernstige bijwerkingen optreden bij de patiënten voor wie de behandeling met een anti-PD-1 medicijn - voornamelijk pembrolizumab en nivolumab - langer dan een jaar aanhoudt. De bijwerkingen kunnen nog optreden bij patiënten 'lang na het stoppen' van de behandeling, schrijven ze ij hun studie analyse.
Kernpunten uit de studie:
- The incidence of delayed immune-related adverse events(irAEs) >12 months after commencing anti-PD1 was 5.3%
- 118 patients had delayed irAEs; these were often high grade (39% G3+) including two delayed irAE-related deaths
- Delayed irAEs were often difficult to manage; 68% required steroids and 23% required an additional immunosuppressive agent
- Most occurred during anti-PD1 therapy (74%), but delayed irAEs were also reported up to 26 months after stopping anti-PD1
Published:March 30, 2021DOI:https://doi.org/10.1016/j.annonc.2021.03.204
Delayed immune-related adverse events with anti-PD1-based immunotherapy in melanoma
Published:March 30, 2021DOI:https://doi.org/10.1016/j.annonc.2021.03.204
Highlightss
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The incidence of delayed immune-related adverse events (irAEs) >12 months after commencing anti-PD1 was 5.3%
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118 patients had delayed irAEs; these were often high grade (39% G3+) including two delayed irAE-related deaths
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Delayed irAEs were often difficult to manage; 68% required steroids and 23% required an additional immunosuppressive agent
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Most occurred during anti-PD1 therapy (74%), but delayed irAEs were also reported up to 26 months after stopping anti-PD1
Abstract
Background
IrAEs typically occur within 4 months of starting anti-PD1-based therapy (anti-PD1 +/- anti-CTLA4), but delayed irAEs (onset >12 months after commencement) can also occur. This study describes the incidence, nature and management of delayed irAE in patients receiving anti-PD1-based immunotherapy.
Methods
Patients with delayed irAEs from 20 centres were studied. The incidence of delayed irAEs was estimated as a proportion of melanoma patients treated with anti-PD1-based therapy and surviving >1 year. Onset, clinical features, management and outcomes of irAEs were examined.
Results
118 patients developed a total of 140 delayed irAEs (20 after initial combination with anti-CTLA4); with an estimated incidence of 5.3% (95% CI 4.0-6.9, 53/999 patients at sites with available data). The median onset of delayed irAE was 16 months (range 12-53). 87 patients (74%) were on anti-PD1 at irAE onset, 15 patients (12%) were <3 months from last dose, 16 patients (14%) were >3 months from last dose of anti-PD1. The most common delayed irAEs were colitis, rash and pneumonitis; 55 of all irAEs (39%) were ≥G3. Steroids were required in 80 patients (68%), as well as an additional immunosuppressive agent in 27 patients (23%). There were two irAE-related deaths: encephalitis with onset during anti-PD1, and a multiple organ-irAE with onset 11 months after ceasing anti-PD1. Early irAEs (<12 months) had also occurred in 69 patients (58%), affecting a different organ from the delayed irAE in 59 patients (86%).
Conclusions
Delayed irAEs occur in a small but relevant subset of patients. Delayed irAEs are often different from previous irAE, may be high grade and can lead to death. They mostly occur in patients still receiving anti-PD1. The risk of delayed irAE should be considered when deciding duration of treatment in responding patients. However, patients who stop treatment may also rarely develop delayed irAE.
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Article Info
Publication History
Accepted: March 28, 2021
Received in revised form: March 9, 2021
Received: November 1, 2020
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2021 Published by Elsevier Ltd on behalf of European Society for Medical Oncology.
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