APHON Pediatric Chemotherapy-Biotherapy Renewal

Targeted Therapy Brentuximab vedotin (Adcetris). Brentuximab vedotin is a conjugated monoclonal antibody that has been approved by the FDA for the treatment of relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. It is also used for the treatment of mycosis fungoides and peripheral T-cell lymphoma that expresses CD30. Brentuximab vedotin links a CD30 antibody to four molecules of the microtubule inhibitor monomethyl auristatin E (MMAE). The drug binds to the cells that express CD30 and forms a complex, which is taken into the CD30-positive cell where it releases its toxic payload of MMAE. MMAE binds to the tubules and disrupts the cellular microtubule network, inducing cell-cycle arrest and apoptosis. Peripheral neuropathy consisting of both motor and sensory neuropathy has been observed with brentuximab vedotin. Signs and symptoms of the peripheral neuropathy that is associated with this conjugated monoclonal antibody include hypesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, and neuropathic pain. Brentuximab vedotin therapy has a black-box warning associated with progressive multifocal leukoencephalopathy. Nursing considerations include monitoring for new- onset signs and symptoms of central nervous system toxicity. These signs and symptoms would include changes in memory, behavior and cognition, motor coordination, and speech, as well as visual disturbances and muscle weakness. Any nurse caring for a patient exhibiting these symptoms should report the symptoms and be prepared to take prompt action following their evaluation by the medical team. Evaluation should include a consultation with the neurology team, along with a brain MRI and lumbar puncture, and possibly a brain biopsy (Corbin et al., 2017; Pastorelli et al., 2013). Dinutuximab (Unituxin). Dinutuximab is a chimeric human-mouse monoclonal antibody used for treatment of high-risk neuroblastoma. It targets GD2, a tumor-associated antigen expressed on the surface of neuroblastoma cells as well as on many “normal” cells, including skin melanocytes, neurons, optic nerves, and peripheral pain fibers (McGinty & Kolesar, 2017). Dinutuximab induces cell death via antibody-dependent cell-mediated cytotoxicity and complement- dependent cytotoxicity, because it binds to GD2 on the surface of neuroblastoma cells as well as the nonmalignant cells mentioned above. It is this action that causes the various neurotoxicities associated with this drug. A neurological ocular toxicity may occur as dinutuximab binds to the GD2 found on the surface of optic nerve cells, resulting in blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and papilledema. Nursing interventions for this toxicity include frequent and thorough assessments, including evaluation of the patient’s pupillary response. Dose reduction, therapy interruption, or treatment discontinuation may be necessary to address this ocular neurotoxicity. Dinutuximab also presents more serious neurotoxicities, including severe neuropathic pain and peripheral neuropathy. Dinutuximab carries a black-box warning for neuropathic pain, which is quite serious. It occurs in more than 50% of patients receiving dinutuximab, and peripheral neuropathy occurs in 2%–9% of patients receiving the drug (McGinty & Kolesar, 2017). This pain may be described as generalized, abdominal, back, or musculoskeletal pain. Some patients report arthralgia, neuralgia, and pain in their extremities. Patients receiving dinutuximab are