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Hematological adverse events with PD-1, PD-L1 inhibitors warrant better management
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Hematological immune-related adverse events associated with PD-1 or PD-L1 inhibitors, such as neutropenia and hemolytic anemia, are rare but potentially fatal and warrant earlier detection and better management, according to a descriptive observational study published in The Lancet Hematology.
“By increasing the activity of the immune system, it is now well known that immune checkpoint blockade can trigger inflammatory side effects that can theoretically reach all organs,” Nicolas Delanoy, MD, of the department of medical oncology at European Georges Pompidou Hospital, and colleagues wrote. “Many studies have described immune-related adverse events affecting the skin, gastrointestinal tract, endocrine glands, liver, lungs, joints, nervous system and muscles, but data about the hemopoietic system remain scarce.”
Researchers screened 948 patients in three French pharmacovigilance databases and found 35 patients (21 men; median age, 65 years; interquartile range, 51-75) with hematological immune-related adverse events related to anti-PD-1 or anti-PD-L1 therapies.
The most common cancer types included melanoma (n = 15), non-small cell lung cancer (n = 12) and lymphoma (n = 4). Treatments included nivolumab (Opdivo, Bristol-Myers Squibb; n= 20), pembrolizumab (Keytruda, Merck; n = 14) and atezolizumab (Tecentriq, Genentech; n = 1).
Clinical description of hematological immune-related adverse events and their frequency served as primary endpoints.
Results showed a low frequency of hematological toxicities (0.5%), including nine patients each with neutropenia, autoimmune hemolytic anemia and immune thrombocytopenia; five patients with pancytopenia or aplastic anemia; two patients with bicytopenia and one patient with red cell aplasia.
Grades of severity included grade 2 (n = 3), grade 3 (n = 5), grade 4 (n = 25) and grade 5 (n = 2). Two patients died of febrile neutropenia related to treatment. Adverse events were resolved in 21 patients.
Study limitations included the fact that it was retrospective and the declarative method of reporting adverse events. Researchers also cited possible underreporting by treating physicians.
“These limitations meant we could not draw any definitive conclusions about the exact frequency, description or distribution of the different types of [hemopoietic adverse events] induced by anti-PD-1 or anti-PD-L1,” Delanoy and colleagues wrote. “Although we note limitations ... this observational study encourages further, in-depth investigations of hematological immune toxicities, to search for biomarkers that can be helpful for earlier detection.”
It will be important for other countries to record these adverse events through new registries under development, John B. Haanen, MD, head of the division of medical oncology and staff scientist in the division of immunology at Netherlands Cancer Institute, and Solange Peters, MD, PhD, head of the thoracic malignancies program in the department of oncology at the University of Lausanne, wrote in an accompanying editorial.
“Collecting and combining information on rare toxicities from these registries is crucial for patients who might be selected for immunotherapies,” Haanen and Peters wrote. “The registries should become worldwide repositories that can be consulted for the incidence, management and outcome of rare severe immune-related adverse events, including hematological toxicities, but also cardiac and neurological events.” – by John DeRosier
Disclosures: Delanoy reports nonfinancial support from Sanofi. Please see the study for all other authors’ relevant financial disclosures. Haanen reports grants and personal fees from the Netherlands Cancer Institute, Neon Therapeutics and Novartis and personal fees from Bayer, Celsius Therapeutics, Gadeta BV, Immunocore, Ipsen, Pfizer and Roche. Peters reports no relevant financial disclosures.
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