Spectrum of Immune Checkpoint Inhibitor Anemias: Results From a Single Center, Early-Phase Clinical Trials Case Series Experience

Abstract

Immune checkpoint inhibitor anemias (ICI-A) are a rare entity which can be potentially life-threatening without prompt identification. The goal of the study is to characterize the presentation, evaluation, and outcomes of ICI therapy in early phase clinical trial setting to guide future research and to develop standardized care guidelines. Retrospective chart review of 333 patients who participated in early phase clinical trials at the University of Texas MD Anderson Cancer Center revealed four cases with ICI-A between 2016 and 2020. We identified a spectrum of four cases which included ICI-related autoimmune hemolytic anemias, hemophagocytic lymphohistiocytosis and thrombotic microangiopathy as a result of combinatory investigational therapies involving ICI. Patient presentation, evaluation, bone marrow pathology, interventions, and clinical course were reviewed. The median time to onset of hematological immune-related adverse events (heme-irAEs) in this retrospective series was 3.5 weeks (2 - 6 weeks). One patient had pre-existing untreated chronic lymphocytic leukemia. Glucocorticoids are an effective first-line treatment in most patients although most patients were not rechallenged but successfully had complete recovery and pursued further non-immunotherapy-based therapies. Cognizance of ICI-A in clinical trial setting is paramount to early recognition of heme-irAEs. Further research is needed to identify and stratify risk factors during clinical trial enrollment and optimal management strategies for immune-mediated hematologic toxicities.

Fever of unknown origin associated with immune checkpoint inhibitors

“…One of the diagnostic criteria for HLH is the presence of a fever higher than 38.5°C. According to our review, patients with ICIs-induced HLH frequently exhibit hyperthermia, with peak temperatures ranging between 38.6°C and 40.5°C ( 115 – 117 , 124 , 130 , 131 ).…”

miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review

“…Indeed, 43% of patients undergoing immunotherapy with ICI develop chronic or long-term adverse events, and up to 9% of ICI-treated patients may face severe or fatal consequences. The most common irAEs include skin toxicities, colitis, hepatitis, pneumonitis, nephritis, and endocrinopathies (i.e., thyroid abnormalities), although other less frequent effects such as cardiac disorders [8,11] may also appear.…”