title: Survivorship in Immune Therapy: Assessing Chronic Immune Toxicities, Health Outcomes, and Functional Status among Long-term Ipilimumab Survivors at a Single Referral Center.
abstract: Ipilimumab, a novel immune checkpoint inhibitor, is associated with long-term survival in approximately 20% of patients with advanced melanoma and is also being evaluated in the adjuvant setting. With this growing cohort of survivors, long-term health outcomes, chronic toxicities, and functional outcomes among survivors treated with ipilimumab need to be defined. Using retrospective medical record abstraction, we evaluated disease status, chronic immune- and non-immune-related health events, pharmacologic management of symptoms, and functional status in patients with melanoma, with overall survival ≥2 years following ipilimumab treatment at Vanderbilt University. Ninety patients received ipilimumab for metastatic disease or as adjuvant therapy between January 2006 and September 2012, and 33 patients survived ≥2 years, with a median overall survival of 60.1 months. Of these, 24 patients were alive at the last follow-up (73%), with 14 patients free of disease (42%). Gastrointestinal and dermatologic adverse events were frequent but largely transient. By contrast, patients with hypophysitis universally required ongoing corticosteroids, although largely remained asymptomatic with appropriate hormone replacement. Surviving patients generally had excellent performance status (ECOG 0-1 in 23 of 24). Chronic neurologic toxicities caused substantial morbidity and mortality in 2 patients who received whole-brain radiotherapy >5 years before analysis, and in one patient with chronic, painful peripheral neuropathy. No previously undescribed cardiac, pulmonary, gastrointestinal, hematologic, or neoplastic safety signals were identified. In conclusion, ipilimumab was associated with largely excellent functional outcomes among long-term survivors. Chronic endocrine dysfunction and occasional neurologic toxicity (primarily associated with whole-brain radiation) were observed in a small number of patients.
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. douglas.b.johnson@vanderbilt.edu.
authors: Douglas B
authors: DB
authors: Johnson
authors: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Debra L
authors: DL
authors: Friedman
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Elizabeth
authors: E
authors: Berry
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Ilka
authors: I
authors: Decker
authors: Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Fei
authors: F
authors: Ye
authors: Department of Quantitative Sciences, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Shilin
authors: S
authors: Zhao
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Alicia K
authors: AK
authors: Morgans
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Igor
authors: I
authors: Puzanov
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Jeffrey A
authors: JA
authors: Sosman
authors: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Christine M
authors: CM
authors: Lovly
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D005076:Exanthema / Q000139:chemically induced; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy*; D009437:Neuralgia / Q000139:chemically induced; D010900:Pituitary Diseases / Q000139:chemically induced; D011537:Pruritus / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab
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