Original ResearchSafety and efficacy of anti-programmed death 1 antibodies in patients with cancer and pre-existing autoimmune or inflammatory disease
Introduction
The immune check-point inhibitors (ICIs, i.e. antibodies against cytotoxic T-lymphocyte–associated protein 4 [CTLA-4] or programmed death 1 [PD-1]) are effective in the treatment of several types of cancer [1], [2], [3], [4], [5]. The clinical success of this immunotherapeutic strategy has confirmed the immune system's role weight in controlling cancer and that the ability of neoplastic cells to hide from the immune system is one of the hallmarks of cancer [6], [7].
With anti-CTLA-4 and anti-PD-1 antibodies, oncologists have been confronted with the occurrence of immune-related adverse events (irAEs) [9], [8], [10], [11]. Interestingly, the occurrence of irAE has been linked to greater anti-tumour effectiveness of anti-PD-1 treatment in patients with advanced melanoma and non–small-cell lung cancer (NSCLC) [16], [17], [18]. Patients with pre-existing autoimmune and/or inflammatory disease (AID) were initially excluded from clinical trials of ICI because of the possible increase of irAE [12]. Despite this initial reluctance, patients with mild-to-moderate pre-existing AID are now often treated with ICI. Recent studies have shown that both anti-CTLA-4 and anti-PD-1 antibodies can be effective AID patients [13], [14], [15]. However, all the data published to date were collected in retrospective studies of small numbers of patients.
Using data from a prospective multicenter registry, we therefore decided to describe and analyse the safety and effectiveness of anti-PD-1 antibodies in patients with a pre-existing AID.
Section snippets
Patients
We described ICI-treated patients with pre-existing AID and compared them with AID-free patient groups in terms of the occurrence of toxicity, overall survival (OS) and the best overall response rate (ORR). The patients had been included in the prospective REISAMIC registry (‘Registry of Severe Adverse Events of Immunomodulating Monoclonal Antibodies in Oncology’) between June 1st, 2014, and December 31st, 2016. REISAMIC includes all patients treated with anti-PD-1 antibodies following
Results
A total of 45 patients enrolled in REISAMIC were assessed (median [IQR] age: 63.3 (56.6–70.7); males: 46.7%; Fig. 1). We then compared the 45 patients enrolled in REISAMIC with 352 AID-free patients included in REISAMIC over the same period.
Discussion
Our results highlighted at least three important points. First, pre-existing AID of mild-to-moderate severity was associated with an elevated risk of an irAE which can occur earlier than in non-AID patients. However, more than half of the patients with AID did not experience a flare of their disease. Second, anti-PD-1 had to be stopped only in 25% of the cases of irAEs and steroids were required in only 6 patients. These results are in accordance with retrospective studies [13], [14]. This
Conclusion
When treated with anti-PD-1 antibodies, patients with pre-existing AID were found to have an elevated risk of irAE and flares. However, with appropriate management, anti-PD-1 antibodies seem to be just as safe and effective in AID patients as in AID-free patients. Our observations highlight the importance of collaboration between oncologists, organ specialists, internists and clinical immunologists for improving patient care.
Conflict of interest statement
JMM is a member of BMS Board consultancy. ER is sub-investigator for BMS, Roche, Novartis, Merk and Amgen. SC received paid expert testimony for AstraZeneca, BMS, Janssen, MSD and Roche. CM acknowledges his participation to advisory boards and is speaker or investigator for Amgen, Astellas, AstraZeneca, Bayer, Celgene, Genentech, Ipsen, Jansen, Lilly, Novartis, Pfizer, Roche, Sanofi and Orion. NG received paid expert testimony for BMS, MSD, AstraZeneca, Merck and Roche. SD received paid expert
Funding support
None.
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Current address: Institut du Thorax Curie Montsouris, Institut Curie, F-75014 Paris, France.