Checkpoint inhibitors

Abstract

Immune checkpoint inhibitors are a class of antineoplastic therapies that unleash immune cells to kill malignant cells. These medications commonly cause immune-related adverse effects due to activated adaptive and innate immune cells, autoantibody production, and/or cytokine dysregulation. Hematologic toxicities are rare and of uncertain mechanism, and therefore management is often based on experiences with familiar conditions involving these perturbed immune responses. Management is challenging because one must attend to the hematologic toxicity while simultaneously attending to the malignancy, with the imperative that therapeutic effects be maintained or minimally interrupted when possible.

Graphical abstract

Figure 1.

How the CTLA-4 inhibitor works. Anti-CTLA-4 therapy blocks inhibitory signals to cytotoxic (CD8+) and helper (Th1 and Th2) T lymphocytes and suppresses the activation of regulatory T cells (CD4/25+). (Reprinted from Kroll et al with permission.)

Figure 2.

How PD-1 and PD-L1 inhibitors work. PD-1/PD-L1 therapies have block inhibitory signals to cytotoxic and helper T lymphocytes, B lymphocytes, natural killer cells, and macrophages and suppress the activation of regulatory T cells. RBCs, red blood cells. (Reprinted from Kroll et al with permission.)

Figure 3.

Management of immune checkpoint inhibitor hematologic toxicity. *Recommended thresholds for holding therapy are 1500/µL neutrophils, 75 000/µL platelets, and 8 g/dL serum hemoglobin concentration. **Please be aware of the possibility of Duffy null associated neutrophil count (previously designated “benign ethnic neutropenia”) among patients of African or Middle Eastern ancestry. CBC, complete blood cell count.