Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy

Journal for ImmunoTherapy of Cancer

Volumn 4, Issue 1, 2016, Pages

  Heinzerling, Lucie ^a   Ott, Patrick A ^b   Hodi, F Stephen ^b   Husain, Aliya N ^c   Tajmir Riahi, Azadeh ^a   Tawbi, Hussein ^d   Pauschinger, Matthias ^e   Gajewski, Thomas F ^c   Lipson, Evan J ^f   Luke, Jason J ^c  

^a UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c UNIVERSITY OF CHICAGO   (United States)

^d UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^e Paracelsus Medical University Nuremberg   (Germany)

^f JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

Cardiomyopathy; Checkpoint inhibitor; Immune related adverse events; Immunotherapy; Ipilimumab; Melanoma; Myocarditis; Nivolumab; Pembrolizumab

Indexed keywords

CARVEDILOL; CORTICOSTEROID; CREATINE KINASE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; FUROSEMIDE; IPILIMUMAB; LEVOTHYROXINE; METHYLPREDNISOLONE; METOPROLOL; NIVOLUMAB; PEMBROLIZUMAB; PROGRAMMED DEATH 1 RECEPTOR; RAMIPRIL; SPIRONOLACTONE; TROPONIN;

ADULT; AGED; ARTICLE; AWARENESS; CARDIOMYOPATHY; CARDIOTOXICITY; CLINICAL ARTICLE; CLINICAL TRIAL (TOPIC); COMPUTER ASSISTED TOMOGRAPHY; CREATININE CLEARANCE; ECHOCARDIOGRAPHY; HEART ARREST; HEART BLOCK; HEART CATHETERIZATION; HEART FAILURE; HEART MUSCLE BIOPSY; HEART MUSCLE FIBROSIS; HISTOLOGY; HUMAN; IMMUNOTHERAPY; MALE; MELANOMA; MONITORING; MULTIPLE ORGAN FAILURE; MYOCARDITIS; NUCLEAR MAGNETIC RESONANCE IMAGING; PATIENT SAFETY; PRIORITY JOURNAL; RETROSPECTIVE STUDY; VERY ELDERLY;

EID: 84997633422     PISSN: None     EISSN: 20511426     Source Type: Journal    
DOI: 10.1186/s40425-016-0152-y     Document Type: Article

References (36)

1. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711-23.
2. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517-26.
3. Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014;32:1020-30.
4. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373:23-34.
5. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369:134-44.
6. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015;372:2521-32.
7. Luke JJ, Callahan MK, Postow MA, Romano E, Ramaiya N, Bluth M, et al. Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience. Cancer. 2013;119:3687-95.
8. Zimmer L, Vaubel J, Mohr P, Hauschild A, Utikal J, Simon J, et al. Phase II DeCOG-study of ipilimumab in pretreated and treatment-naive patients with metastatic uveal melanoma. PLoS One. 2015;10:e0118564.
9. Larkin J, D'Angelo S, Sosman JA, Lebbe C, Brady B, Neyns B, et al. Efficacy and safety of nivolumab (NIVO) monotherapy in the treatment of advanced mucosal melanoma. Pigment Cell Melanoma Res. 2016;28:789.
10. Min L, Hodi FS. Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis. Cancer Immunol Res. 2014;2:15-8.
11. Prieto PA, Yang JC, Sherry RM, Hughes MS, Kammula US, White DE, et al. CTLA-4 blockade with ipilimumab: long-term follow-up of 177 patients with metastatic melanoma. Clin Cancer Res. 2012;18:2039-47.
12. Lipson EJ. Re-orienting the immune system: Durable tumor regression and successful re-induction therapy using anti-PD1 antibodies. Oncoimmunology. 2013;2:e23661.
13. Graziani G, Tentori L, Navarra P. Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharmacol Res. 2012;65:9-22.
14. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109-17.
15. Voskens C, Cavallaro A, Erdmann M, Dippel O, Kaempgen E, Schuler G, et al. Anti-cytotoxic T-cell lymphocyte antigen-4-induced regression of spinal cord metastases in association with renal failure, atypical pneumonia, vision loss, and hearing loss. J Clin Oncol. 2012;30:e356-7.
16. Fadel F, El KK, Knebelmann B. Anti-CTLA4 antibody-induced lupus nephritis. N Engl J Med. 2009;361:211-2.
17. Hunter G, Voll C, Robinson CA. Autoimmune inflammatory myopathy after treatment with ipilimumab. Can J Neurol Sci. 2009;36:518-20.
18. Vogel WV, Guislain A, Kvistborg P, Schumacher TN, Haanen JB, Blank CU. Ipilimumab-induced sarcoidosis in a patient with metastatic melanoma undergoing complete remission. J Clin Oncol. 2012;30:e7-e10.
19. Wilgenhof S, Neyns B. Anti-CTLA-4 antibody-induced Guillain-Barre syndrome in a melanoma patient. Ann Oncol. 2011;22:991-3.
20. Maker AV, Phan GQ, Attia P, Yang JC, Sherry RM, Topalian SL, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12:1005-16.
21. Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, et al. Cutaneous, gastrointestinal, hepatic, endocrine and renal side effects of anti-PD-1 therapy. Eur J Cancer (in press).
22. Chan MM, Kefford RF, Carlino M, Clements A, Manolios N. Arthritis and tenosynovitis associated with the anti-PD1 antibody pembrolizumab in metastatic melanoma. J Immunother. 2015;38:37-9.
23. Zimmer L, Goldinger SM, Hofmann L., Loquai C, Ugurel S, Thomas I, et al. Neurological, respiratory, musculoskeletal, cardiac and ocular side effects of anti-PD-1 therapy. Eur J Cancer (in press).
24. Voskens CJ, Goldinger SM, Loquai C, Robert C, Kaehler KC, Berking C, et al. The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network. PLoS One. 2013;8:e53745.
25. Yun S, Vincelette ND, Mansour I, Hariri D, Motamed S. Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication. Case Rep Oncol Med. 2015;2015:794842.
26. Geisler BP, Raad RA, Esaian D, Sharon E, Schwartz DR. Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome. J Immunother Cancer. 2015;3:4.
27. Laubli H, Balmelli C, Bossard M, Pfister O, Glatz K, Zippelius A. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J Immunother Cancer. 2015;3:11.
28. Tarrio ML, Grabie N, Bu DX, Sharpe AH, Lichtman AH. PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis. J Immunol. 2012;188:4876-84.
29. Lucas JA, Menke J, Rabacal WA, Schoen FJ, Sharpe AH, Kelley VR. Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice. J Immunol. 2008;181:2513-21.
30. Wang J, Okazaki IM, Yoshida T, Chikuma S, Kato Y, Nakaki F, et al. PD-1 deficiency results in the development of fatal myocarditis in MRL mice. Int Immunol. 2010;22:443-52.
31. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319-22.
32. Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9:1477-83.
33. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3:541-7.
34. Love VA, Grabie N, Duramad P, Stavrakis G, Sharpe A, Lichtman A. CTLA-4 ablation and interleukin-12 driven differentiation synergistically augment cardiac pathogenicity of cytotoxic T lymphocytes. Circ Res. 2007;101:248-57.
35. Linette GP, Stadtmauer EA, Maus MV, Rapoport AP, Levine BL, Emery L, et al. Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. Blood. 2013;122:863-71.
36. Iwama S, De RA, Callahan MK, Slovin SF, Wolchok JD, Caturegli P. Pituitary expression of CTLA-4 mediates hypophysitis secondary to administration of CTLA-4 blocking antibody. Sci Transl Med. 2014;6:230ra45.