The Price of Tumor Control: An Analysis of Rare Side Effects of Anti-CTLA-4 Therapy in Metastatic Melanoma from the Ipilimumab Network
Caroline J. Voskens,Simone M. Goldinger,Carmen Loquai,Caroline Robert,Katharina C. Kaehler,Carola Berking,Tanja Bergmann,Clemens L. Bockmeyer,Thomas Eigentler,Michael Fluck,Claus Garbe,Ralf Gutzmer,Stephan Grabbe,Axel Hauschild,Rüdiger Hein,Gheorghe Hundorfean,Armin Justich,Ullrich Keller,Christina Klein,Christine Mateus,Peter Mohr,Sylvie Paetzold,Imke Satzger,Dirk Schadendorf,Marc Schlaeppi,Gerold Schuler,Beatrice Schuler-Thurner,Uwe Trefzer,Jens Ulrich,Julia Vaubel,Roger von Moos,Patrik Weder,Tabea Wilhelm,Daniela Göppner,Reinhard Dummer,Lucie Heinzerling,Lucie Heinzerling +36 more
TLDR
In this article, a wide spectrum of Ipilimumab-induced adverse events including drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis were documented.Abstract:
BACKGROUND: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers.
METHODS AND FINDINGS: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment.
CONCLUSION: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects.read more
Citations
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
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Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review.
Rimda Wanchoo,Sabine Karam,Nupur N. Uppal,Valerie S. Barta,Gilbert Deray,Craig Devoe,Vincent Launay-Vacher,Kenar D. Jhaveri +7 more
TL;DR: Although initially thought to be rare, the incidence rates of renal toxicities might be higher as identified by recent studies, Steroids appear to be effective in treating the immune-related adverse effects noted with these agents.
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Immune-related adverse events with immune checkpoint blockade: a comprehensive review
Jean-Marie Michot,Camille Bigenwald,Stéphane Champiat,Michael Collins,Franck Carbonnel,Sophie Postel-Vinay,Amandine Berdelou,Andreea Varga,Ratislav Bahleda,Antoine Hollebecque,Christophe Massard,Alina Fuerea,Vincent Ribrag,A. Gazzah,J.P. Armand,N Amellal,Eric Angevin,Nicolas Noel,Celine Boutros,Christine Mateus,Caroline Robert,Jean-Charles Soria,Aurélien Marabelle,Olivier Lambotte +23 more
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Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma
Abstr Act,Sagar Lonial,Meletios A. Dimopoulos,Antonio Palumbo,Darrell White,Sebastian Grosicki,Ivan Spicka,Adam Walter‑Croneck,Philippe Moreau,Maria-Victoria Mateos,Hila Magen,Andrew Belch,Donna E. Reece,Meral Beksac,Andrew Spencer,Heather Oakervee,Robert Z. Orlowski,Masafumi Taniwaki,Christoph Röllig,Hermann Einsele,Ka Lung Wu,Anil K. Singhal,Jesús F. San Miguel,Morio Matsumoto,Jessica Katz,Eric Bleickardt,Valerie Poulart,Kenneth C. Anderson,Paul G. Richardson +28 more
TL;DR: Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death.
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Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.
Filipe Martins,Filipe Martins,Latifyan Sofiya,Gerasimos P. Sykiotis,Faiza Lamine,Michel H. Maillard,Montserrat Fraga,Keyvan Shabafrouz,Camillo Ribi,Anne Cairoli,Yan Guex-Crosier,Thierry Kuntzer,Olivier Michielin,Solange Peters,Georges Coukos,Georges Coukos,François Spertini,John A. Thompson,Michel Obeid,Michel Obeid +19 more
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References
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疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma
Caroline Robert,Luc Thomas,Igor Bondarenko,Steven J. O'Day,Jeffrey S. Weber,Claus Garbe,Céleste Lebbé,Jean Francois Baurain,Alessandro Testori,Jean-Jacques Grob,Neville Davidson,Jon M. Richards,Michele Maio,Axel Hauschild,Wilson H. Miller,Pere Gascón,Michal Lotem,Kaan Harmankaya,Ramy Ibrahim,Stephen Francis,Tai-Tsang Chen,R. Humphrey,Axel Hoos,Jedd D. Wolchok +23 more
TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
Journal ArticleDOI
Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab
TL;DR: A detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy are provided.
Journal ArticleDOI
Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study
Jedd D. Wolchok,Bart Neyns,Gerald P. Linette,Sylvie Negrier,Jose Lutzky,Luc Thomas,William Waterfield,Dirk Schadendorf,Michael Smylie,Troy H. Guthrie,Jean-Jacques Grob,Jason Chesney,Kevin M. Chin,Kun Chen,Axel Hoos,Steven J. O'Day,Céleste Lebbé +16 more
TL;DR: Ipilimumab elicited a dose-dependent effect on efficacy and safety measures in pretreated patients with advanced melanoma, lending support to further studies at a dose of 10 mg/kg.
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