Cobimetinib

Cobimetinib Reactions 1704, p117 - 2 Jun 2018 Focal necrotising myopathy with dropped-head syndrome: case report A 72-year-old man developed focal necrotising myopathy with dropped-head syndrome following treatment with cobimetinib [route not stated]. The man, who had Parkinson’s disease and NRAS-mutated advanced melanoma, started receiving treatment with cobimetinib 60 mg/day, 3 weeks and 1 week off. His concurrent treatment included nivolumab, levodopa, unspecified monoamine oxidase inhibitor and anti-cholinergic agent. One month after initiation of cobimetinib treatment, he presented with incapsular pain and axial fatigue with cervical hypotonia. Subsequent laboratory investigation revealed a slight grade 1 liver enzyme elevation, more marked on the AST. Fifteen days later, a clinical reassessment revealed worsening of clinical symptoms. The cervical muscle strength was found to have decreased to 4/5. Laboratory test revealed increased level of CPK up to 1011 U/L (n < 308). Subsequent PET CT revealed intense uptake in the cervical muscles, which was not present on previous images 2.5 months earlier, before the start of cobimetinib. Consequently, a muscle biopsy of the pathological cervical muscles was performed with ultrasound guidance. Histological examination revealed some necrotic muscle fibers and focal regenerative basophilic fibers dispersed throughout the bundles, without pathological inflammation but with a very mild increased and abnormal sarcoplasmic expression of human leukocyte antigen class 1 with atrophic fiber enhancement. Consequently, he was diagnosed with focal necrotising myopathy with dropped-head syndrome considered to be secondary to cobimetinib treatment. Therefore cobimetinib was withdrawn. Within 5 days, CPK levels reduced to half. Within 2 weeks, his CPK levels normalised and other symptoms disappeared progressively. The man continued to receive treatment with nivolumab at the same dosage. Subsequently, due to partial response in melanoma, cobimetinib was reintroduced at a dose of 40 mg/day. Author comment: "We describe a case of focal necrotizing myopathy with ‘dropped-head syndrome’ induced by Gauci M-L, et al. Focal necrotizing myopathy with ’dropped-head syndrome’ induced by cobimetinib in metastatic melanoma. Melanoma Research 27: 511-515, No. 5, Oct 2017. Available from: URL: http://doi.org/10.1097/ CMR.0000000000000377 - France 803323089 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reactions Weekly Springer Journals

Cobimetinib

Reactions Weekly , Volume 1704 (1) – Jun 2, 2018
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Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer International Publishing AG, part of Springer Nature
Subject
Medicine & Public Health; Drug Safety and Pharmacovigilance; Pharmacology/Toxicology
ISSN
0114-9954
eISSN
1179-2051
D.O.I.
10.1007/s40278-018-46760-4
Publisher site
See Article on Publisher Site

Abstract

Reactions 1704, p117 - 2 Jun 2018 Focal necrotising myopathy with dropped-head syndrome: case report A 72-year-old man developed focal necrotising myopathy with dropped-head syndrome following treatment with cobimetinib [route not stated]. The man, who had Parkinson’s disease and NRAS-mutated advanced melanoma, started receiving treatment with cobimetinib 60 mg/day, 3 weeks and 1 week off. His concurrent treatment included nivolumab, levodopa, unspecified monoamine oxidase inhibitor and anti-cholinergic agent. One month after initiation of cobimetinib treatment, he presented with incapsular pain and axial fatigue with cervical hypotonia. Subsequent laboratory investigation revealed a slight grade 1 liver enzyme elevation, more marked on the AST. Fifteen days later, a clinical reassessment revealed worsening of clinical symptoms. The cervical muscle strength was found to have decreased to 4/5. Laboratory test revealed increased level of CPK up to 1011 U/L (n < 308). Subsequent PET CT revealed intense uptake in the cervical muscles, which was not present on previous images 2.5 months earlier, before the start of cobimetinib. Consequently, a muscle biopsy of the pathological cervical muscles was performed with ultrasound guidance. Histological examination revealed some necrotic muscle fibers and focal regenerative basophilic fibers dispersed throughout the bundles, without pathological inflammation but with a very mild increased and abnormal sarcoplasmic expression of human leukocyte antigen class 1 with atrophic fiber enhancement. Consequently, he was diagnosed with focal necrotising myopathy with dropped-head syndrome considered to be secondary to cobimetinib treatment. Therefore cobimetinib was withdrawn. Within 5 days, CPK levels reduced to half. Within 2 weeks, his CPK levels normalised and other symptoms disappeared progressively. The man continued to receive treatment with nivolumab at the same dosage. Subsequently, due to partial response in melanoma, cobimetinib was reintroduced at a dose of 40 mg/day. Author comment: "We describe a case of focal necrotizing myopathy with ‘dropped-head syndrome’ induced by Gauci M-L, et al. Focal necrotizing myopathy with ’dropped-head syndrome’ induced by cobimetinib in metastatic melanoma. Melanoma Research 27: 511-515, No. 5, Oct 2017. Available from: URL: http://doi.org/10.1097/ CMR.0000000000000377 - France 803323089 0114-9954/18/1704-0001/$14.95 Adis © 2018 Springer International Publishing AG. All rights reserved Reactions 2 Jun 2018 No. 1704

Journal

Reactions WeeklySpringer Journals

Published: Jun 2, 2018

References

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