Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
LETTER TO THE EDITOR - DOCUMENTING A CASE
Year : 2011  |  Volume : 7  |  Issue : 3  |  Page : 346-348

Rituximab induced myocardial infarction: A fatal drug reaction


1 Department of Cardiology, JIPMER, Puducherry, India
2 Department of Medical Oncology, JIPMER, Puducherry, India

Date of Web Publication2-Nov-2011

Correspondence Address:
Palamalai Arunprasath
Department of Cardiology, JIPMER, Puducherry
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.87003

Rights and Permissions

How to cite this article:
Arunprasath P, Gobu P, Dubashi B, Satheesh S, Balachander J. Rituximab induced myocardial infarction: A fatal drug reaction. J Can Res Ther 2011;7:346-8

How to cite this URL:
Arunprasath P, Gobu P, Dubashi B, Satheesh S, Balachander J. Rituximab induced myocardial infarction: A fatal drug reaction. J Can Res Ther [serial online] 2011 [cited 2020 Jun 4];7:346-8. Available from: http://www.cancerjournal.net/text.asp?2011/7/3/346/87003

Sir,

Rituximab is chimeric anti-CD20 antibody used commonly in the treatment of various neoplasms, such as lymphomas and also in the treatment of rheumatoid arthritis. Infusion reactions are common following rituximab administration. Cardiotoxicity in the form of arrthymias is described usually as an adverse reaction. We report here a rare fatal infusion reaction, acute myocardial infarction following rituximab therapy for the treatment of testicular lymphoma.

A 60-year-man having diabetes, presented with swelling in the right scrotum for 3 months. The patient was evaluated and diagnosed to have testicular lymphoma and subsequently underwent high orchidectomy. There were no stage B symptoms. Histopathology and immunohistochemistry revealed diffuse large B cell lymphoma with CD20, CD10 positive, and Tdt negative CD3-stained structure lymphocytes with increased ki67. Postoperative chemotherapy was planned.

Prechemotherapy evaluation was done as per the protocol. The patient had no cardiac symptoms prior to chemotherapy. Baseline electrocardiogram and echocardiogram were normal. After informed consent, the patient was started on rituximab. He developed febrile reaction with rigors immediately following infusion. This reaction was managed with antihistamines and hydrocortisone injection. The patient complained of severe chest pain and sweating 15 min later. Urgent electrocardiogram revealed ST elevation in lateral leads, which did not subside even after stopping rituximab infusion and administration with sublingual nitrates. Pain persisted for more than 30 min and repeat electrocardiogram showed extensive anterior wall myocardial infarction [Figure 1]. The patient was shifted to coronary care unit and thrombolyzed with streptokinase 1.5 million units over 45 min. There was more than 50% ST segment resolution at 90 min, suggestive of successful thrombolysis. Echocardiography showed regional wall motion abnormality of left anterior descending artery (LAD) territory with moderate left ventricular dysfunction (40%). Coronary angiography done at the time of discharge revealed spontaneous dissection of proximal left anterior descending artery with residual thrombus but with TIMI III flow [Figure 2] and [Figure 3]. No other significant coronary lesion was detected.
Figure 1: Electrocardiogram showing extensive anterior wall myocardial infarction

Click here to view
Figure 2: Coronary angiogram showing thrombus in the proximal left anterior descending artery (anteroposterior caudal view)

Click here to view
Figure 3: Coronary angiogram showing dissection in the proximal left anterior descending artery (Right anterior oblique cranial view)

Click here to view


Rituximab is a chimeric anti-CD20 antibody with high affinity for CD20 surface antigen on B lymphocytes of both normal and malignant origin. [ 1 ] It is used commonly against various hematologic malignancies, CD20 positive diffuse large B cell lymphoma, and stage III-IV follicular lymphoma. B lymphocytes play a pivotal role in the pathogenesis of rheumatoid arthritis and so rituximab is an approved agent in the management of patients with rheumatoid arthritis.

Rituximab is generally well tolerated if given with adequate premedication except for minor infusion reactions. Fatal infusion reactions are rare, although well documented in the literature and occurred 80% of time with first infusion. [ 1 ] Risk of fatal infusion reactions is higher with high baseline CD20 positive B lymphocyte load. [2] Fatal infusion reactions include hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, and cardiogenic shock. In severe cases, life-threatening cytokine release syndrome in the form of bronchospasm, hypotension, urticaria, and angioedema occurs.

Cardiovascular toxicity in the form of cardiac dysrhythmias has been reported in 8% of patients treated with rituximab for lymphoma. Arrhythmias that occur may be due to release of cytokines, such as interleukin-6 and tumor necrosis factor-alpha. [3] Myocardial infarction is one of the fatal infusion reactions reported. The proposed mechanism for acute coronary syndrome following rituximab infusion is the release of cytokines, which cause vasoconstriction, platelet activation, and/or rupture of atherosclerotic plaque. [4] In our case it is likely that the patient had a pre-existing vulnerable plaque. Following the cytokine release with rituximab infusion the vulnerable plaque would have spontaneously ruptured or dissected creating an acute total occlusion and myocardial infarction. The angiographic evidence of spontaneous dissection and residual thrombus indicates this as a likely mechanism [Figure 2] and [Figure 3]. Vulnerable plaque rupture can happen in high-risk patients who have risk factors for coronary artery disease or pre-existing coronary artery disease. Anecdotal case reports on acute coronary syndrome following rituximab therapy have been reported in pre-existing coronary artery disease patients. In our case, the patient had diabetes and advanced age as risk factors but never had any symptoms of ischemic heart disease. Meticulous screening for ischemic heart disease may be necessary in high-risk subsets before starting on rituximab therapy.

 
 > References Top

1.Genentech: Products - Product Information - Rituxan Full Prescribing Information [Internet]. Available from: http://www.gene.com/gene/products/information/oncology/ritu. [Last accessed on 2010 Oct 27].  Back to cited text no. 1
    
2.Winkler U, Jensen M, Manzke O, Schultz H, Diehl V, Engert A. Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti CD20 monoclonal antibody. Blood 1999;94:2217-24.  Back to cited text no. 2
    
3.Foran JM, Rohaitner AZ, Cunningham D, Popescu RA, Solal-Celigny P, Ghielmini M, et al. European Phase II study of rituximab (chimeric anti-CD20 monoclonal antibody) for patients with newly diagnosed mantle cell lymphoma and previously treated mantle cell lymphoma, immunocytoma, and small B lymphocytic lymphoma. J Clin Oncol 2000;18:317-24.  Back to cited text no. 3
    
4.Aronson JK. Meyler's Side Effects of Cardiovascular Drugs. 1 st ed. Oxford: Elsevier; 2009.  Back to cited text no. 4
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]


This article has been cited by
1 Cardiovascular Risk and the Use of Biologic Agents in Rheumatoid Arthritis
Debbie T. Lim,Amy C. Cannella,Kaleb D Michaud,Ted R. Mikuls
Current Rheumatology Reports. 2014; 16(11)
[Pubmed] | [DOI]
2 Adverse cardiac events to monoclonal antibodies used for cancer therapy: The risk of Kounis syndrome
Nicholas G Kounis,George D Soufras,Grigorios Tsigkas,George Hahalis
OncoImmunology. 2014; 3(1): e27987
[Pubmed] | [DOI]
3 Rituximab-Vincristine Chemotherapy-Induced Acute Anterior Wall Myocardial Infarction with Cardiogenic Shock
Ambuj Roy,Naveen Khanna,Nagendra Boopathy Senguttuvan
Texas Heart Institute Journal. 2014; 41(1): 80
[Pubmed] | [DOI]
4 Modulation of bevacizumab-induced toxicity for cultured human corneal fibroblasts
Kim, E.K. and Kang, S.W. and Kim, J.Y. and Min, K. and Kim, T.-I.
Investigative Ophthalmology and Visual Science. 2013; 54(6): 3922-3931
[Pubmed]
5 Biologics and the cardiovascular system: A double-edged sword
Roubille, C. and Martel-Pelletier, J. and Haraoui, B. and Tardif, J.-C. and Pelletier, J.-P.
Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry. 2013; 12(1): 68-82
[Pubmed]
6 Reversal of cardiomyopathy with tocilizumab in a case of HIV-negative Castlemanęs disease
Louise Man,Ranjit K. Goudar
European Journal of Haematology. 2013; 91(3): 273
[Pubmed] | [DOI]
7 Myocardial infarction after rituximab infusion
Dimitri Renard,Luc Cornillet,Giovanni Castelnovo
Neuromuscular Disorders. 2013; 23(7): 599
[Pubmed] | [DOI]
8 Myocardial infarction after rituximab infusion
Renard, D. and Cornillet, L. and Castelnovo, G.
Neuromuscular Disorders. 2013; 23(7): 599-601
[Pubmed]
9 Rituximab
Reactions Weekly. 2012; 1387(1): 30
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Article Figures
  In this article
>References

 Article Access Statistics
    Viewed4808    
    Printed142    
    Emailed2    
    PDF Downloaded321    
    Comments [Add]    
    Cited by others 9    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]