PracticeUpdate: Diabetes

AACE 2018 19

High Incidence of Ipilimumab- Induced Hypophysitis Documented in Large Cohort Study of PatientsWithMetastatic Melanoma Older and treatment-naive patients were specifically at higher risk N ew research presented at AACE 2018 found a high incidence of ipilimumab-induced hypophysitis (IH) in patients with melanoma. In particular, two groups were associated with a higher risk of IH: older men and individuals with no prior cancer therapy. Ipilimumab, a cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhib- itor, was approved by the U.S. Food and Drug Administration in 2011 for the treatment of unresectable or metastatic melanoma. Research is cur- rently underway, assessing its effectiveness in treating tumors in numerous other cancers including prostate, ovarian, and gastric. “Immune checkpoint inhibitors have recently become a cornerstone for the treatment of differ- ent advanced cancers, and the number of indications for use is growing exponentially to include many solid and hematologic malignancies,” Roula S. Zahr, MD, of the Oregon Health and Science University School of Med- icine in Portland, told Elsevier’s PracticeUpdate . “Given the broad and expanding use of this novel therapy,” she noted, “it is critical to understand the spectrum of possible side effects in order to promptly recognize and treat any complication in this highly complex patient population.” Research indicates that up to 17% of patients will develop ipilimumab-IH, 1 but at present, little is known about which patients are more likely to develop the disease or how to treat the life-threatening complication. The retrospec- tive study conducted by Dr. Zahr and her colleagues involved a review of 117 melanoma patients who received ipilimumab between 2011–2016. Of these patients, 15 (12.8%) developed IH. “We found a high incidence of hypophysitis in our cohort,” said Dr. Zahr. “Treatment-naive patients were at higher risk for hypophysitis than patients who received prior cancer therapy, while advanced age increased the risk in males but not females. Survival was not different between hypophysitis and non-hypophysitis patients.” Specifically, no difference was found between genders (13.51% in males versus 11.63% in females), and no patient who received systemic cancer therapy prior to ipilimumab developed IH versus 15 (17.2%) patients with- out prior therapy (P = .011). Among male patients, those with IH were older than those without (mean 67.7 versus 56.4, respectively; P = .02). Between the two groups of patients, no difference was found with respect to seven criteria: race, ethnicity, body mass index, diabetes or autoimmune disease at baseline, number of ipilimumab cycles given, presence of a primary melanoma lesion, or BRAF mutation status. The median survival time for IH patients was 45.0 months compared with 29.5 months (P = .253) for those without IH. “There are no significant identifiable risk factors that could alert physicians to this potentially life-threatening complication during cancer immunother- apy,” said Dr. Zahr. “Our study highlights the need to establish protocols for regular biochemical and radiological screening during both clinical trials and in clinical practice when using immune checkpoint inhibitors.” Reference 1. Dillard T, Yedinak CG, Alumkal J, Fleseriu M. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary 2010;13:29-38. www.practiceupdate.com/c/68801

• hsCRP: 8.60 at baseline versus 5.61 at week 24 (–3.00 change, P < .0001) • white blood cell count (cells/cu.mm): 9092.86 vs 8558.95 (–523.90 change, P = .008) • ESR (mm/hr): 30.06 vs 27.05 (–2.81 change, P = .048) Total cholesterol, LDL cholesterol, non-HDL choles- terol, and triglycerides were reduced significantly in both groups. Dr. Pareek and his colleagues found that HCQ was well tolerated, with a total of 36 individuals reporting 70 adverse events. The majority were gastrointestinal and mild in intensity. Hypoglycemia was reported in 6 individuals, and these incidents were mild in intensity. Dose reduction was required in 2 individuals. The study showed that the benefits of HCQ were significantly greater in individuals with higher inflam- matory load, Dr. Pareek and his colleagues noted, suggesting “further comparative studies on HCQ and other OHAs [oral hypoglycemic agents] are required to distinguish between anti-inflammatory effects result- ing from better glucose control and effects related to intrinsic anti-inflammatory actions.” www.practiceupdate.com/c/68814

VOL. 2 • NO. 3 • 2018