PURPOSE: The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH. METHODS: All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined. RESULTS: Overall, 250 patients (median age 71 years; range 30-87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5-38.0; P = 0.0002) and ipilimumab-nivolumab combination therapy (OR 61.2; 95% CI 7.9-1275.3; P < 0.0001). CONCLUSION: Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient's prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab-nivolumab combination therapy.
PURPOSE: The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH. METHODS: All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined. RESULTS: Overall, 250 patients (median age 71 years; range 30-87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5-38.0; P = 0.0002) and ipilimumab-nivolumab combination therapy (OR 61.2; 95% CI 7.9-1275.3; P < 0.0001). CONCLUSION: Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient's prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab-nivolumab combination therapy.
Authors: Xin Yang; Goska Leslie; Alicja Doroszuk; Sandra Schneider; Jamie Allen; Brennan Decker; Alison M Dunning; James Redman; James Scarth; Inga Plaskocinska; Craig Luccarini; Mitul Shah; Karen Pooley; Leila Dorling; Andrew Lee; Muriel A Adank; Julian Adlard; Kristiina Aittomäki; Irene L Andrulis; Peter Ang; Julian Barwell; Jonine L Bernstein; Kristie Bobolis; Åke Borg; Carl Blomqvist; Kathleen B M Claes; Patrick Concannon; Adeline Cuggia; Julie O Culver; Francesca Damiola; Antoine de Pauw; Orland Diez; Jill S Dolinsky; Susan M Domchek; Christoph Engel; D Gareth Evans; Florentia Fostira; Judy Garber; Lisa Golmard; Ellen L Goode; Stephen B Gruber; Eric Hahnen; Christopher Hake; Tuomas Heikkinen; Judith E Hurley; Ramunas Janavicius; Zdenek Kleibl; Petra Kleiblova; Irene Konstantopoulou; Anders Kvist; Holly Laduca; Ann S G Lee; Fabienne Lesueur; Eamonn R Maher; Arto Mannermaa; Siranoush Manoukian; Rachel McFarland; Wendy McKinnon; Alfons Meindl; Kelly Metcalfe; Nur Aishah Mohd Taib; Jukka Moilanen; Katherine L Nathanson; Susan Neuhausen; Pei Sze Ng; Tu Nguyen-Dumont; Sarah M Nielsen; Florian Obermair; Kenneth Offit; Olufunmilayo I Olopade; Laura Ottini; Judith Penkert; Katri Pylkäs; Paolo Radice; Susan J Ramus; Vilius Rudaitis; Lucy Side; Rachel Silva-Smith; Valentina Silvestri; Anne-Bine Skytte; Thomas Slavin; Jana Soukupova; Carlo Tondini; Alison H Trainer; Gary Unzeitig; Lydia Usha; Thomas van Overeem Hansen; James Whitworth; Marie Wood; Cheng Har Yip; Sook-Yee Yoon; Amal Yussuf; George Zogopoulos; David Goldgar; John L Hopper; Georgia Chenevix-Trench; Paul Pharoah; Sophia H L George; Judith Balmaña; Claude Houdayer; Paul James; Zaki El-Haffaf; Hans Ehrencrona; Marketa Janatova; Paolo Peterlongo; Heli Nevanlinna; Rita Schmutzler; Soo-Hwang Teo; Mark Robson; Tuya Pal; Fergus Couch; Jeffrey N Weitzel; Aaron Elliott; Melissa Southey; Robert Winqvist; Douglas F Easton; William D Foulkes; Antonis C Antoniou; Marc Tischkowitz Journal: J Clin Oncol Date: 2019-12-16 Impact factor: 44.544
Authors: Anna Oh; Dang M Tran; Leann C McDowell; Dor Keyvani; Jay Andrew Barcelon; Oscar Merino; Leslie Wilson Journal: J Manag Care Spec Pharm Date: 2017-06