Journal article
Ipilimumab-induced hypophysitis, a single academic center experience
Pituitary, Vol.22(5), pp.488-496
10/01/2019
DOI: 10.1007/s11102-019-00978-4
PMID: 31327112
Abstract
Background Immune checkpoint inhibitors, single or in combination, have recently become a cornerstone for the treatment of many malignancies. Ipilimumab, a CTLA-4 inhibitor, was initially FDA approved for treatment of unresectable or metastatic melanoma and subsequently in combination therapy for other cancers. Ipilimumab-induced hypophysitis (IH) risk of development varies in different studies between 0 and 17%. Furthermore, little is known on how to predict which patients will develop IH and its impact on efficacy of Ipilimumab and survival for these patients. Here we reviewed IH and its impact on progression-free survival (PFS) and overall survival (OS). Methods Retrospective, IRB- approved review of consecutive 117 melanoma patients who received ipilimumab between 2011 and 2016 was undertaken. Demographic and clinical characteristics, treatment timing and doses, time to progression after therapy, and survival data were reviewed. Patients were predefined in two groups: patients with and without IH. Descriptive statistics were used to summarize the demographic and clinical characteristics of the study sample. All values are shown as means and standard deviation [mean (SD)] unless indicated otherwise. P < 0.05 was considered to be statistically significant. Results Of the 117 patients, 15 (12.8%) with a median age of 62.1 years developed IH. In the IH cohort, 10 (66.7%) were male and were significantly older than females (median 67.7 vs. 50.8; P = 0.009). This difference was not seen in non-IH group. Male patients with IH were significantly older than males without IH (67.7 vs. 56.4 years, P = 0.020), however this difference was not observed in females. No patient who received prior cancer systemic therapy (0/30) developed IH vs. 17.2% (15/72) without prior therapy developed IH (OR 0.00; 95% CI 0.00 to 0.73, P = 0.011). Between IH and non-IH patients, there was no difference in gender, race, ethnicity, BMI, diabetes or autoimmune disease at baseline, number of administered ipilimumab cycles, presence of primary melanoma lesion, or BRAF status. IH and non-IH patients had a similar median PFS (8.1 vs. 6.8 months, HR = 0.51, 95% CI 0.24 to 1.05 P = 0.062) and OS (53.3 vs. 29.5 months; HR 0.66, 95% CI 0.30 to 1.46; P = 0.307). Conclusion In this study of melanoma patients treated with Ipilimumab, risk of developing IH was high (almost 13%). Older age in men and no prior cancer therapy were associated with IH higher risk. Development of IH was not associated with PFS or OS. Increased use of immune checkpoint inhibitors in the future will impact IH overall risk, thus awareness is needed. Given the lack of reliable identifiable risk factors, close monitoring of signs and symptoms after each therapy cycle is critical for early detection and treatment of hypophysitis.
Details
- Title: Subtitle
- Ipilimumab-induced hypophysitis, a single academic center experience
- Creators
- Travis Snyders - University of Iowa Hospitals and ClinicsDaniel Chakos - University of Iowa Hospitals and ClinicsUmang Swami - Huntsman Cancer InstituteEmile Latour - Oregon Health & Science UniversityYiyi Chen - Oregon Health & Science UniversityMaria Fleseriu - Oregon Health & Science UniversityMohammed Milhem - University of Iowa Hospitals and ClinicsYousef Zakharia - University of Iowa Hospitals and ClinicsRoula Zahr - Oregon Health & Science University
- Resource Type
- Journal article
- Publication Details
- Pituitary, Vol.22(5), pp.488-496
- Publisher
- Springer Nature
- DOI
- 10.1007/s11102-019-00978-4
- PMID
- 31327112
- ISSN
- 1386-341X
- eISSN
- 1573-7403
- Number of pages
- 9
- Grant note
- P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) NCI P30CA069533 / Biostatistics Shared Resource, Knight Cancer Institute
- Language
- English
- Date published
- 10/01/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359593702771
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