Hematologic immune-related adverse events with immune checkpoint inhibition are rare but serious
medwireNews: Hematologic immune-related adverse events (hem-irAEs) are rare but potentially life-threatening complications of anti-programmed death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) immunotherapy, according to a large observational study.
Writing in The Lancet Hematology, researchers Jean-Marie Michot (Université Paris-Saclay, Villejuif, France) and colleagues note: “Given the increasing number of patients expected to be treated for cancer in the coming years, anti-PD-1 or anti-PD-L1 should be understood as a potential cause of immunological cytopenia.”
Of 948 consecutive adults treated with these immune checkpoint inhibitors within three French pharmacovigilance databases, 35 experienced grade 2 or worse treatment-related hem-irAEs. And in the largest database, REISMAIC (which contributed 745 patients to the study), only four individuals had treatment-related hem-irAEs, yielding a frequency of 0.5%.
Despite the rarity of such events, they were often serious and even life-threatening, with 27 (77%) patients experiencing hem-irAEs of grade 4 or worse. Two patients died from hem-irAEs related to anti-PD-1 immunotherapy, and 28 (80%) permanently stopped anti-PD-1/L1 therapy.
Following resolution, seven (20%) of the 35 individuals were rechallenged with the same class of anti-PD-1/L1 therapy, with the same adverse event occurring in three (43%) patients. “[R]echallenge thus should be carefully considered and patients should be closely monitored,” note Michot and colleagues.
The most common types of hem-irAE were neutropenia, autoimmune hemolytic anemia, and immune thrombocytopenia, each of which occurred in nine (26%) of the 35 patients. The other events were pancytopenia or aplastic anemia (n=5), bicytopenia (n=2), and pure red cell aplasia (n=1).
Hem-irAEs occurred at a median of 10.1 weeks after starting an anti-PD-1/anti-PD-L1 agent. The range, however, was 0.9 to 198.0 weeks, which the researchers say suggests “that haem-irAEs can potentially occur at any time.”
The current findings have further clinical implications, they continue: “Except for the increase in eosinophil blood count that can be regarded as a non-clinically significant event, our study supports that any new blood count abnormality after anti-PD-1 or anti-PD-L1 must be considered as a potential clinically significant event.”
In an accompanying comment, John Haanen (The Netherlands Cancer Institute, Amsterdam) and Solange Peters (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland) stress that given the rarity of these adverse events, registries are important for providing insight into the efficacy and toxicity of new therapies.
“Collecting and combining information on rare toxicities from these registries is crucial for patients who might be selected for immunotherapies. The registries should become worldwide repositories that can be consulted for the incidence, management, and outcome of rare severe immune-related adverse events, including haematological toxicities, but also cardiac and neurological events.”
By Catherine Booth
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