Thrombotic Thrombocytopenic Purpura due to Checkpoint Inhibitors.

Ipilimumab is a monoclonal antibody that enhances the efficacy of the immune system by targeting a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which is a protein receptor that downregulates the immune system. Nivolumab is also a humanized monoclonal antibody that targets another protein receptor that prevents activated T cells from attacking the cancer; this receptor is called programmed cell death 1 (PD-1). The FDA approved ipilimumab combined with nivolumab as a frontline therapy for patients with metastatic melanoma or renal cell carcinoma and as a second-line therapy for patients with microsatellite instability-high (MSI-H) metastatic colon cancer. Immune-related adverse events such as autoimmune colitis, pneumonitis, hepatitis, nephritis, hypophysitis, and thyroiditis may occur during or weeks to months after therapy. We report a case of thrombotic thrombocytopenic purpura (TTP) in a patient with metastatic renal cell carcinoma following one cycle of ipilimumab and nivolumab. Only one case report of ipilimumab-induced TTP exists in the medical literature. With the wide use of immunotherapy to treat cancers, physicians need to be aware of this rare immune-related adverse event.

Plasmapheresis therapy for rare but potentially fatal reaction to rituximab.

Rituximab (Rituxan), a genetically engineered chimeric murine and human IgG1 monoclonal antibody directed against CD20 antigen, is an emerging drug used for a wide spectrum of disease processes and found to be relatively safe. We report a near-fatal reaction to rituximab, which started 30 min after infusion and worsened over 24 to 48 h, resulting in hemodynamic and respiratory compromise that necessitated both intubation and high-dose vasopressors. Subsequent treatment with plasmapheresis helped stabilize and improve the patient's clinical condition, and the patient was discharged home on hospital day 5. There is no specific treatment for these severe and sometimes fatal reactions except supportive care with plasmapheresis. With the increased use of rituximab therapy in the medical management of numerous diseases, those in the medical community need to be cognizant of the rare fatal or near-fatal infusion reaction and the benefit that may accrue from plasmapheresis therapy.