Pembrolizumab-induced myasthenia gravis: A fatal case report

被引:54
作者
March, Katherine L. [1 ,2 ]
Samarin, Michael J. [1 ]
Sodhi, Amik [1 ,3 ]
Owens, Ryan E. [4 ]
机构
[1] Methodist Univ Hosp, Dept Pharm, Memphis, TN USA
[2] Univ Tennessee, Ctr Hlth Sci, Dept Clin Pharm, Memphis, TN 38163 USA
[3] Univ Tennessee, Ctr Hlth Sci, Div Pulm Crit Care & Sleep Med, Memphis, TN 38163 USA
[4] Univ Oklahoma, Hlth Sci Ctr, Dept Pharm Clin & Adm Sci, Norman, OK 73019 USA
关键词
Myasthenia gravis; pembrolizumab; neurology; monoclonal antibody; oncology; EXACERBATION; ANTIBODY; SAFETY; CANCER; PD-1;
D O I
10.1177/1078155216687389
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Pembrolizumab, a monoclonal antibody which inhibits the programmed cell death 1 receptor, has been shown to efficaciously enhance pre-existing immune responses to malignancies. However, safety concerns must also be considered as pembrolizumab use has been associated with several life-threatening immune-related adverse events (irAEs). We report a fatal case of pembrolizumab-induced myasthenia gravis in a patient with no prior myasthenia gravis history. Case report A 63-year-old male presented with right eyelid drooping, puffiness, blurred vision, and shortness of breath two weeks after an initial infusion of pembrolizumab. He was subsequently diagnosed with new onset acetylcholine-receptor positive myasthenia gravis. Despite aggressive treatment with corticosteroids, pyridostigmine, intravenous immunoglobulin, and plasmapheresis, the patient clinically deteriorated and ultimately expired from acute respiratory failure after a 12-day hospitalization. Discussion Current package labeling for pembrolizumab warns against various irAEs associated with its use including pneumonitis, colitis, and endocrinopathies. To date, only one case of new onset myasthenia gravis and two case reports of myasthenia gravis exacerbation have been identified. This case further highlights the mortality risk associated with development of irAEs. Conclusion While rare, evidence for the development of MG associated with pembrolizumab is growing. Prompt recognition of symptoms and discontinuation of pembrolizumab is necessary to help improve prognosis.
引用
收藏
页码:146 / 149
页数:4
相关论文
共 11 条
[1]   Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer [J].
Brahmer, Julie R. ;
Tykodi, Scott S. ;
Chow, Laura Q. M. ;
Hwu, Wen-Jen ;
Topalian, Suzanne L. ;
Hwu, Patrick ;
Drake, Charles G. ;
Camacho, Luis H. ;
Kauh, John ;
Odunsi, Kunle ;
Pitot, Henry C. ;
Hamid, Omid ;
Bhatia, Shailender ;
Martins, Renato ;
Eaton, Keith ;
Chen, Shuming ;
Salay, Theresa M. ;
Alaparthy, Suresh ;
Grosso, Joseph F. ;
Korman, Alan J. ;
Parker, Susan M. ;
Agrawal, Shruti ;
Goldberg, Stacie M. ;
Pardoll, Drew M. ;
Gupta, Ashok ;
Wigginton, Jon M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2455-2465
[2]   Pathophysiology of myasthenia gravis [J].
Hughes, BW ;
De Casillas, MLM ;
Kaminski, HJ .
SEMINARS IN NEUROLOGY, 2004, 24 (01) :21-30
[3]   Myasthenia Gravis Induced by Ipilimumab in Patients With Metastatic Melanoma [J].
Johnson, Douglas B. ;
Saranga-Perry, Vita ;
Lavin, Patrick J. M. ;
Burnette, W. Bryan ;
Clark, Stephen W. ;
Uskavitch, David R. ;
Wallace, Deborah E. ;
Dickson, Mark A. ;
Kudchadkar, Ragini R. ;
Sosman, Jeffrey A. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (33) :E122-E124
[4]   Exacerbation of myasthenia gravis in a patient with melanoma treated with pembrolizumab [J].
Lau, K. H. Vincent ;
Kumar, Aditya ;
Yang, Irene Hwa ;
Nowak, Richard J. .
MUSCLE & NERVE, 2016, 54 (01) :157-161
[5]  
Merck & Co. Inc, 2016, KEYTR PEMBR
[6]   A METHOD FOR ESTIMATING THE PROBABILITY OF ADVERSE DRUG-REACTIONS [J].
NARANJO, CA ;
BUSTO, U ;
SELLERS, EM ;
SANDOR, P ;
RUIZ, I ;
ROBERTS, EA ;
JANECEK, E ;
DOMECQ, C ;
GREENBLATT, DJ .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1981, 30 (02) :239-245
[7]   PD-1 and PD-1 ligands: from discovery to clinical application [J].
Okazaki, Taku ;
Honjo, Tasuku .
INTERNATIONAL IMMUNOLOGY, 2007, 19 (07) :813-824
[8]   Tumor Immunotherapy Directed at PD-1 [J].
Ribas, Antoni .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2517-2519
[9]   Safety, Activity, and Immune Correlates of Anti-PD-1 Antibody in Cancer [J].
Topalian, Suzanne L. ;
Hodi, F. Stephen ;
Brahmer, Julie R. ;
Gettinger, Scott N. ;
Smith, David C. ;
McDermott, David F. ;
Powderly, John D. ;
Carvajal, Richard D. ;
Sosman, Jeffrey A. ;
Atkins, Michael B. ;
Leming, Philip D. ;
Spigel, David R. ;
Antonia, Scott J. ;
Horn, Leora ;
Drake, Charles G. ;
Pardoll, Drew M. ;
Chen, Lieping ;
Sharfman, William H. ;
Anders, Robert A. ;
Taube, Janis M. ;
McMiller, Tracee L. ;
Xu, Haiying ;
Korman, Alan J. ;
Jure-Kunkel, Maria ;
Agrawal, Shruti ;
McDonald, Daniel ;
Kollia, Georgia D. ;
Gupta, Ashok ;
Wigginton, Jon M. ;
Sznol, Mario .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (26) :2443-2454
[10]   Myasthenia gravis exacerbation associated with pembrolizumab [J].
Zhu, Julia ;
Li, Yuebing .
MUSCLE & NERVE, 2016, 54 (03) :506-507