TY  - JOUR
A1  - Voskens, Caroline J.
A1  - Goldinger, Simone M.
A1  - Loquai, Carmen
A1  - Robert, Caroline
A1  - Kähler, Katharina C.
A1  - Berking, Carola
A1  - Bergmann, Tanja Regina
A1  - Bockmeyer, Clemens Luitpold
A1  - Eigentler, Thomas Kurt
A1  - Fluck, Michael
A1  - Garbe, Claus
A1  - Gutzmer, Ralf
A1  - Grabbe, Stephan
A1  - Hauschild, Axel
A1  - Hein, Rüdiger
A1  - Hundorfean, Gheorghe
A1  - Justich, Armin
A1  - Keller, Ullrich
A1  - Klein, Christina
A1  - Mateus, Christine
A1  - Mohr, Peter
A1  - Pätzold, Sylvie
A1  - Satzger, Imke
A1  - Schadendorf, Dirk
A1  - Schlaeppi, Marc
A1  - Schuler, Gerold
A1  - Schuler-Thurner, Beatrice
A1  - Trefzer, Uwe
A1  - Ulrich, Jens
A1  - Vaubel, Julia
A1  - Moos, Roger von
A1  - Weder, Patrik
A1  - Wilhelm, Tabea
A1  - Göppner, Daniela
A1  - Dummer, Reinhard
A1  - Heinzerling, Lucie
T1  - The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network
T2  - PLoS One
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28370
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-283704
SN  - 1932-6203
N1  - Copyright: © 2013 Voskens et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 8
IS  - (1): e53745
PB  - PLoS
CY  - Lawrence, Kan.
ER  -