RESUMEN
Immune cell engager therapeutic strategies using bioengineered molecules to redirect immune cells into tumor are starting to demonstrate promising clinical activity in multiple early phase trials across numerous targets and a range of solid tumor types. These therapies, however, carry the risk of exaggerated cytokine-mediated on-target off-tumor adverse events that require highly specialized inpatient facilities. We report here the Royal Marsden experience of treating patients with advanced solid tumors on early phase immune engager clinical trials in a dedicated inpatient facility, focusing specifically on patterns of cytokine-mediated toxicity seen and proposing a risk-mitigation algorithm for the safe, feasible and scalable delivery of these therapies.
Asunto(s)
Inmunoterapia , Neoplasias , Humanos , Neoplasias/terapia , Citocinas/metabolismo , Servicios de SaludRESUMEN
A 67-year-old man with metastatic prostate cancer and underlying asymptomatic pancytopenia presented with a 1-week history of general malaise, left leg weakness and facial numbness. Initial brain imaging demonstrated two rim-enhancing lesions felt to represent intracerebral metastasis. Following neurosurgical referral, a multidisciplinary meeting decision was made for best supportive care and dexamethasone was given. He developed multiple cutaneous lesions, which on incision and drainage revealed Nocardia farcinica Repeat brain imaging showed enlargement of the existing cavitating lesions and appearance of new lesions, now typical of cerebral abscesses. A diagnosis of disseminated nocardiosis with cutaneous and intracerebral infection was reached. He started taking empirical treatment with intravenous meropenem, co-trimoxazole and subsequent addition of amikacin, with little improvement. On further review of sensitivities, moxifloxacin was added. Following over 1 month of antimicrobial treatment, his neurological symptoms, cutaneous lesions and repeat MRI of the brain had improved.