Delanoy N, et al. - Researchers conducted a detailed investigation into haematological immune-related adverse events (irAEs) [haem-irAEs] induced by anti-programmed cell death 1 (PD-1) or anti-programmed cell death ligand 1 (PD-L1). According to findings, although a rare occurrence of haem-irAEs induced by PD-1 or PD-L1 inhibitors was reported but these hold potential to threaten the patient's life. Clinically, such adversities present most commonly as neutropenia, autoimmune haemolytic anaemia, immune thrombocytopenia, and aplastic anaemia. It is justified to aim at earlier detection and better management of such adverse events.

Methods

• This was a descriptive observational study.
• Researchers used 3 French pharmacovigilance databases: the Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie (REISAMIC; a prospective registry of patients treated with anti-PD-1 or anti-PD-L1 at a single centre), the ImmunoTOX committee of Gustave Roussy (a national referral database of suspected irAEs in patients treated with immunotherapy), and the registry of the Centre de Référence des Cytopénies Auto-Immunes de l'Adulte (CeReCAI; a national database of autoimmune cytopenias) to identify participants.
• Participants were consecutive patients aged at least 18 years with grade 2 or worse haem-irAEs induced by anti-PD-1 or anti-PD-L1 immunotherapy.
• A central committee reviewed cases.
• Using the Common Terminology Criteria for Adverse Events (version 4.03), severity of adverse events was evaluated and were classed as certainly or probably related to anti-PD-1 or anti-PD-L1 therapy.
• Clinical description of haem-irAEs and their frequency, as reported in all databases and in the prospective REISAMIC registry, respectively, were analyzed as primary endpoint.

Results

• The cases (948 patients) registered in the 3 databases were screened from June 27, 2014, to June 29, 2018 (745 from REISAMIC, 190 from the ImmunoTOX committee, and 13 from CeReCAI).
• This study included a total of 35 patients, including 21 men and 14 women, with haem-irAEs related to anti-PD-1 or anti-PD-L1.
• In the REISAMIC registry, haem-irAEs were seen in 4 of 745 patients treated with anti-PD-1 or anti-PD-L1, giving a frequency of 0·5%.
• Median age in the 35 patients was 65 years (IQR 51–75), and melanoma (15 [43%] patients), non-small-cell lung cancer (12 [34%] patients), and lymphoma (four [11%] patients) comprised the most common tumour types.
• Nivolumab, pembrolizumab, and atezolizumab were received by 20 (57%) patients, 14 (40%), and one (3%), respectively.
• The most common types of haem-irAE (each in nine patients [26%]) seen in the 35 patients were neutropenia, autoimmune haemolytic anaemia, and immune thrombocytopenia, followed by pancytopenia or aplastic anaemia (five patients [14%]), bicytopenia (one patients with thrombocytopenia plus anaemia and one patient with neutropenia plus anaemia [6%]), and pure red cell aplasia (one patient [3%]).
• Findings revealed that the maximum grade of severity was grade 2 in three (9%) patients, grade 3 in five (14%) patients, and grade 4 in 25 (71%) patients; death of 2 (6%) patients due to febrile neutropenia was reported during haem-irAE related to anti-PD-1.
• In 21 (60%) of the 35 patients, resolve of haem-irAEs was reported.