Cobimetinib
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Dropped head syndrome following off-label treatment: case report A 71-year-old woman developed dropped head syndrome following off-label treatment with cobimetinib for Erdheim‐Chester disease (ECD). The woman, who was diagnosed with ECD in 2013, started receiving peginterferon. However, her disease progressed. Thereafter, she started receiving off-label treatment with cobimetinib [route not stated] 40 mg/day for 3 weeks on and 1 week off. Her baseline creatine phosphokinase (CPK) level was 24 U/L. At cycle 1 on day 15, she was noted to have significant neck stiffness. Laboratory parameters were stable. At cycle 1 on day 28, she developed left‐sided neck pain with limiting the ability to lift the head. A CT of the neck showed only moderate left foraminal C4‐C5 narrowing and mild degenerative changes. Prior to the second cycle, she complained of increased neck pain and reduced mobility. Based on these findings and clinical presentation, she was diagnosed with cobimetinib induced dropped head syndrome. The woman was treated with methylprednisolone, following which her neck pain resolved. At cycle 2 on day 8, she experienced persistent neck pain. Her CPK level was elevated to 150 U/L. Her cobimetinib therapy was stopped. Twenty-one days following the discontinuation of cobimetinib, improvement in her neck mobility was observed, and the level of CPK was decreased to 44 U/L. At day 50 following the discontinuation of cobimetinib, she was re-challenged with cobimetinib 20mg daily for 3 weeks on and 1 week off. On day 8 of the re-challenge, continued improvement of neck strength and mobility was noted. All laboratory findings were within a normal range. On day 22, she was found to have a slight worsening of the head drop along with a full range of motion requiring focused effort to achieve neck mobility. The level of CPK was increased to 37 U/L. During her off week, she showed improvement. Based on these findings, the dose of cobimetinib 20 mg/day, 2 weeks on and 2 weeks off was recommended. At follow-up on cycle 1 on day 15 of the rechallenge, she reported an overall improvement in head drop without any new focal complaints. However, the level of CPK was elevated (79 U/L). Prior to initiation of cycle 2, CPK level was decreased to approximately twice the baseline value, and her symptoms improved. The most recent positron emission tomography (PET) CT scan showed resolution of cardiac fluorodeoxyglucose (FDG) avidity without new lesions. She continued to the attenuate re-challenge schedule with cobimetinib. Minor and intermittent recovery of symptoms approximately day 4–6 of each cycle was observed with complete resolution by day 28. Author comment: "Here‐in, we describe our experience with a. . .patient treated with cobimetinib that developed dropped head syndrome." King AC, et al. Cobimetinib-induced "dropped head syndrome" and subsequent disease management in an Erdheim-Chester patient. Clinical Case Reports 7: 1989-1993, No. 10, Oct 2019. Available from: URL: http://doi.org/10.1002/ 8034376
