Mikael Guedj1, Astrid Quéant1, Elisa Funck-Brentano2, Nora Kramkimel3, Judith Lellouch4, Dominique Monnet1, Christine Longvert2, Amelie Gantzer2, Antoine P Brézin1. 1. Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital, Paris, France2Faculté de Médecine, Université Paris Descartes, Paris, France. 2. Department of Dermatology, Ambroise Paré Hospital, Boulogne-Billancourt, France. 3. Faculté de Médecine, Université Paris Descartes, Paris, France4Department of Dermatology, Cochin Hospital, Paris, France. 4. Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital, Paris, France.
Abstract
IMPORTANCE: This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma. OBJECTIVE: To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy. DESIGN, SETTING, AND PATIENTS: In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital. MAIN OUTCOMES AND MEASURES: Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced. RESULTS: Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients. CONCLUSIONS AND RELEVANCE: This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their vision.
IMPORTANCE: This case series highlights the risk of uveitis in patients treated with vemurafenib for unresectable or metastatic cutaneous melanoma. OBJECTIVE: To assess the occurrence and severity of uveitis as an adverse effect of vemurafenib therapy. DESIGN, SETTING, AND PATIENTS: In this observational small case series, data were collected successively from May 1, 2012, through February 31, 2013, from patients with clinical signs of ocular inflammation treated with vemurafenib at the Department of Ophthalmology, Cochin-Hôtel-Dieu Hospital. MAIN OUTCOMES AND MEASURES: Patients' demographics, vemurafenib dosages, and the intervals between the onset of treatment and the first ocular symptoms were recorded. The characteristics of ocular inflammatory manifestations were analyzed. The effect of the discontinuation of vemurafenib therapy on ocular manifestations was assessed, as well as the effect of rechallenging when vemurafenib was reintroduced. RESULTS: Seven patients (mean [SD] age, 74.7 [4.0] years) had uveitis. The vemurafenib dose was 960 mg twice per day in 6 patients and a half dose in 1 patient. The mean (SD) time until the appearance of ocular signs was 5.6 (2.3) months (range, 19 days to 7 months), and inflammation ranged from mild or low-grade anterior uveitis to severe explosive panuveitis complicated by retinal detachment. Signs of ocular inflammation were always bilateral. Optical coherence tomography revealed a macular edema in only 1 of the 7 patients. Clinical improvement occurred when vemurafenib therapy was stopped in 5 of 7 patients. The rechallenge at treatment reintroduction was positive in 2 of 7 patients. CONCLUSIONS AND RELEVANCE: This small case series highlights that uveitis can be a noteworthy adverse effect of vemurafenib therapy in patients with metastatic cutaneous melanoma. However, these cases of uveitis were usually restricted to the anterior segment and manageable with local corticosteroid therapy, which justified the continuation of vemurafenib therapy because the benefits regarding the patients' survival were greater than the risk to their vision.