Pembrolizumab-Related Side Effects: Acute Renal Failure and Severe Neurological Toxicity

Abstract

Immunotherapy with immune checkpoint inhibitors represents nowadays a marked improvement in cancer treatment. Nevertheless, they can cause severe toxicities that put the patient at high risk, often requiring aggressive treatment. We present the case of a female patient who developed a severe immune-related adverse reaction to Pembrolizumab prescribed for melanoma treatment. Her array of symptoms, which presented a few days after last drug administration, consisted of severe neurological deficit, severe renal failure, polymyositis, and hyperthyroidism. Treatment required the immediate interruption of the trigger drug, infusion of high dose steroids, renal replacement therapy, plasmapheresis, and methimazole, as will be further discussed.

Keywords: adverse reaction; neurological toxicity; pembrolizumab; pembrolizumab toxicity; renal toxicity.

Figure 1

CTLA-4 and PD-1 inhibitor mechanism after the activation of T-cells through their “primed” T-cell receptor, as well as a co-regulatory signal delivered by the B7 family of receptors (immune checkpoints). Notes: CTLA-4, up-regulated shortly after activation, negatively regulates T-cell activation, binding to B7 molecules on APCs surface, during the priming phase of T-cell response within the lymph nodes. B7 molecules binding to CD28, instead, generates the opposite, activating signals. During the effector phase of T-cell immune-response, PD-1 is expressed on T-cells and binds to either of its ligands (PD-L1 or PD-L2), which are primarily expressed within inflamed tissues and the tumor microenvironment, resulting in inhibition of T-cell activity. Antibodies direct to CTLA-4 or PD-1/PD-L1 can activate T-cells with specificity for cancer cells. Abbreviations: MHC, major histocompatibility complex; PD-1, programmed cell death-1; CTLA-4, cytotoxic T-lymphocyte antigen-4; TCR, T-cell receptor.