Julien Haroche1, Fleur Cohen-Aubart2, Jean-François Emile2, Philippe Maksud2, Aurélie Drier2, Dan Tolédano2, Stéphane Barete2, Frédéric Charlotte2, Philippe Cluzel2, Jean Donadieu2, Neïla Benameur2, Philippe A Grenier2, Sophie Besnard2, Jean-Paul Ory2, François Lifermann2, Ahmed Idbaih2, Brigitte Granel2, Bruno Graffin2, Baptiste Hervier2, Laurent Arnaud2, Zahir Amoura2. 1. Julien Haroche, Fleur Cohen-Aubart, Philippe Maksud, Aurélie Drier, Dan Tolédano, Stéphane Barete, Frédéric Charlotte, Philippe Cluzel, Neïla Benameur, Philippe A. Grenier, Ahmed Idbaih, Baptiste Hervier, Laurent Arnaud, and Zahir Amoura, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière; Philippe Maksud, Stéphane Barete, Frédéric Charlotte, Philippe Cluzel, Philippe A. Grenier, Ahmed Idbaih, Julien Haroche, Fleur Cohen-Aubart, Baptiste Hervier, Laurent Arnaud, and Zahir Amoura, Paris VI University Pierre et Marie Curie; Jean Donadieu, AP-HP, Hôpital Trousseau, French National Center for Histiocytosis, Paris; Jean-François Emile, EA4340-BCOH, Versailles University, and AP-HP, Hôpital Ambroise Paré, Boulogne; Sophie Besnard, Centre Hospitalier Universitaire de Rennes, Pontchaillou University Hospital, Rennes Cedex; Jean-Paul Ory, Centre Hospitalier Régional de Vesoul, Vesoul; François Lifermann, Hôpital de Dax-Côte d'Argent, Dax; Brigitte Granel, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille; and Bruno Graffin, Hôpital d'Instruction des Armées Legouest, Metz, France. julien.haroche@psl.aphp.fr. 2. Julien Haroche, Fleur Cohen-Aubart, Philippe Maksud, Aurélie Drier, Dan Tolédano, Stéphane Barete, Frédéric Charlotte, Philippe Cluzel, Neïla Benameur, Philippe A. Grenier, Ahmed Idbaih, Baptiste Hervier, Laurent Arnaud, and Zahir Amoura, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière; Philippe Maksud, Stéphane Barete, Frédéric Charlotte, Philippe Cluzel, Philippe A. Grenier, Ahmed Idbaih, Julien Haroche, Fleur Cohen-Aubart, Baptiste Hervier, Laurent Arnaud, and Zahir Amoura, Paris VI University Pierre et Marie Curie; Jean Donadieu, AP-HP, Hôpital Trousseau, French National Center for Histiocytosis, Paris; Jean-François Emile, EA4340-BCOH, Versailles University, and AP-HP, Hôpital Ambroise Paré, Boulogne; Sophie Besnard, Centre Hospitalier Universitaire de Rennes, Pontchaillou University Hospital, Rennes Cedex; Jean-Paul Ory, Centre Hospitalier Régional de Vesoul, Vesoul; François Lifermann, Hôpital de Dax-Côte d'Argent, Dax; Brigitte Granel, Assistance Publique-Hôpitaux de Marseille, Hôpital Nord, Marseille; and Bruno Graffin, Hôpital d'Instruction des Armées Legouest, Metz, France.
Abstract
PURPOSE: Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. PATIENTS AND METHODS: Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). RESULTS: All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. CONCLUSION: Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.
PURPOSE: Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. PATIENTS AND METHODS: Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). RESULTS: All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. CONCLUSION:Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months.
Authors: S Mojdeh Mirmomen; Arlene Sirajuddin; Moozhan Nikpanah; Rolf Symons; Anna K Paschall; Ioannis Papageorgiou; William A Gahl; Kevin O'Brien; Juvianee I Estrada-Veras; Ashkan A Malayeri Journal: Eur Radiol Date: 2018-05-07 Impact factor: 5.315
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Authors: Moozhan Nikpanah; Lauren Kim; S Mojdeh Mirmomen; Rolf Symons; Ioannis Papageorgiou; William A Gahl; Kevin O'Brien; Juvianee I Estrada-Veras; Ashkan A Malayeri Journal: Eur Radiol Date: 2018-03-19 Impact factor: 5.315
Authors: Benjamin H Durham; Damien Roos-Weil; Claude Baillou; Fleur Cohen-Aubart; Akihide Yoshimi; Makoto Miyara; Matthias Papo; Zofia Hélias-Rodzewicz; Nathalie Terrones; Neval Ozkaya; Ahmet Dogan; Raajit Rampal; Fanny Urbain; Lucie Le Fèvre; Eli L Diamond; Christopher Y Park; Thomas Papo; Frédéric Charlotte; Guy Gorochov; Valérie Taly; Olivier A Bernard; Zahir Amoura; Omar Abdel-Wahab; François M Lemoine; Julien Haroche; Jean-François Emile Journal: Blood Date: 2017-05-31 Impact factor: 22.113
Authors: Svetlana A Protsenko; Anna I Semionova; Yuri I Komarov; Svetlana N Aleksakhina; Alexandr O Ivantsov; Aglaya G Iyevleva; Evgeny N Imyanitov Journal: Invest New Drugs Date: 2015-08-20 Impact factor: 3.850