Cytokine-release syndrome is a symptom complex associated with the use of many monoclonal antibodies. Commonly referred to as an infusion reaction, it results from the release of cytokines from cells targeted by the antibody as well as immune effector cells recruited to the area. When cytokines are released into the circulation, systemic symptoms such as fever, nausea, chills, hypotension, tachycardia, asthenia, headache, rash, scratchy throat, and dyspnea can result. In most patients, the symptoms are mild to moderate in severity and are managed easily. However, some patients may experience severe, life-threatening reactions that result from massive release of cytokines. Severe reactions occur more commonly during the first infusion in patients with hematologic malignancies who have not received prior chemotherapy; severe reactions are marked by their rapid onset and the acuity of associated symptoms. Massive cytokine release is an oncologic emergency, and special precautions must be taken to prevent life-threatening complications. This article will present an overview of the etiology and management of cytokine-release syndrome in patients receiving monoclonal antibodies to better prepare oncology nurses to safely care for such patients.
Berlex. (2005). Campath® (alemtuzumab) [Package insert]. Montville, NJ: Author.
Biogen Idec & Genentech, Inc. (2006). Rituxan® (rituximab) [Package insert]. Cambridge, MA, and South San Francisco, CA: Authors.
Byrd, J.C., Murphy, T., Howard, R.S., Lucas, M.S., Goodrich, A., Park, K., et al. (2001). Rituximab using a thrice weekly dosing schedule in B-cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity. <i>Journal of Clinical Oncology, 19</i>, 2153-2164.
Byrd, J.C., Peterson, B.L., Morrison, V.A., Park, K., Jacobson, R., Hoke, E., et al. (2003). Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: Results from Cancer and Leukemia Group B 9712 (CALGB 9712). <i>Blood, 101</i>, 6-14.
Byrd, J.C., Waselenko, J.K., Maneatis, T.J., Murphy, T., Ward, F.T., Monahan, B.P., et al. (1999). Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: Association with increased infusion-related side effects and rapid blood tumor clearance. <i>Journal of Clinical Oncology, 17</i>, 791-795.
DiJulio, J.E. (2001). Monoclonal antibodies: Overview and use in hematologic malignancies. In. P.T. Rieger (Ed.), <i>Biotherapy: A comprehensive overview</i> (2nd ed., pp. 283-316). Sudbury, MA: Jones and Bartlett.
Dillman, R.O. (2002). Radiolabeled anti-CD20 monoclonal antibodies for the treatment of B-cell lymphoma. <i>Journal of Clinical Oncology, 20</i>, 3545-3557.
Dillman, R.O. (2003). Monoclonal antibody therapy. In R.K. Oldham (Ed.), <i>Principles of cancer biotherapy</i> (4th ed., pp. 329-390). Dordrecht, The Netherlands: Kluwer Academic.
Ekmekcioglu, S., Grimm, E.A., & Kurzrock, R. (2006). Cytokines and hematopoietic growth factors. In D.W. Kufe, R.C. Bast, Jr., W.N. Hait, W.K. Hong, R.E. Pollock, R.R. Weichselbaum, et al. (Eds.), <i>Cancer medicine</i> (7th ed., pp. 744-769). Hamilton, Canada: B.C. Decker.
Greenberger, P.A. (2006). Drug allergy. <i>Journal of Allergy and Clinical Immunology, 117</i>(2, Suppl.), S464-S470.
Hainsworth, J.D. (2003). Safety of rituximab in the treatment of B-cell malignancies: Implications for rheumatoid arthritis. <i>Arthritis Research and Therapy, 5</i>(Suppl. 4S), S12-S16.
Jeyarajah, D.R., & Thistlethwaite, J.R., Jr. (1993). General aspects of cytokine-release syndrome: Timing and incidence of symptoms. <i>Transplantation Proceedings, 25</i>(2, Suppl. 1), 16-20.
Kosits, C., & Callaghan, M. (2000). Rituximab: A new monoclonal antibody therapy for non-Hodgkin's lymphoma. <i>Oncology Nursing Forum, 27</i>, 51-59.
Kunzmann, V., Ruediger, T., Hallek, M., Mueller-Hermelink, H.K., & Wilhelm, M. (2001). Tumor cell agglutination and not solely cytokine release as mechanism of adverse reactions during anti-CD20 monoclonal antibody (Idec-C2B8, rituximab) treatment. <i>Blood, 98</i>, 1991-1992.
Liossis, S.N., & Tsokos, G.C. (2005). Monoclonal antibodies and fusion proteins in medicine. <i>Journal of Allergy and Clinical Immunology, 116</i>, 721-729.
Maloney, D.G., Grillo-Lopez, A.J., Bodkin, D.J., White, C.A., Liles, T.M., Royston, I., et al. (1997). Idec-C2B8: Results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. <i>Journal of Clinical Oncology, 15</i>, 3266-3274.
Morris, J.C., & Holland, J.F. (2000). Oncologic emergencies. In R.C. Bast, Jr., D.W. Kufe, R.E. Pollock, R.R. Weichselbaum, J.F. Holland, & E. Frei (Eds.), <i>Cancer medicine</i> (5th ed., pp. 2433-2453). Hamilton, Canada: B.C. Decker.
National Cancer Institute. (2005). <i>Understanding cancer series: The immune system.</i> Retrieved May 30, 2006, from <a target="_blank" href='http://www.cancer.gov/cancertopics/understandingcancer/immunesystem/'>ht...
Norman, D.J., Chatenoud, L., Cohen, D., Goldman, M., & Shield, C.F., III. (1993). Consensus statement regarding OKT3-induced cytokine-release syndrome and human antimouse antibodies. <i>Transplantation Proceedings, 25</i>(2, Suppl. 1), 89-92.
Oldham, R.K. (2003). Current concepts in immunology. In R.K. Oldham (Ed.), <i>Principles of cancer biotherapy</i> (4th ed., pp. 93-109). Dordrecht, The Netherlands: Kluwer Academic.
Petryk, M., & Grossbard, M.L. (2000). Rituximab therapy of B-cell neoplasms. <i>Clinical Lymphoma, 1</i>, 186-194.
Press, O.W., Leonard, J.P., Coiffier, B., Levy, R., & Timmerman, J. (2001). Immunotherapy of non-Hodgkin's lymphomas. <i>Hematology</i>, 221-240.
Rieger, P.T. (2001a). Monoclonal antibodies: Applications in solid tumors and other diseases. In. P.T. Rieger (Ed.), <i>Biotherapy: A comprehensive overview</i> (2nd ed., pp. 317-355). Sudbury, MA: Jones and Bartlett.
Rieger, P.T. (2001b). Patient management. In. P.T. Rieger (Ed.), <i>Biotherapy: A comprehensive overview</i> (2nd ed., pp. 461-505). Sudbury, MA: Jones and Bartlett.
Roskos, L.K., Davis, C.G., & Schwab, G.M. (2004). The clinical pharmacology of therapeutic monoclonal antibodies. <i>Drug Development Research, 61</i>, 108-120.
Schmidt, K.V., & Wood, B.A. (2003). Trends in cancer therapy: Role of monoclonal antibodies. <i>Seminars in Oncology Nursing, 19</i>, 169-179.
Szlosarek, P.W., & Balkwill, F.R. (2003). Tumour necrosis factor α: A potential target for the therapy of solid tumors. <i>Lancet Oncology, 4,</i> 565-573.
van der Kolk, L.E., Grillo-Lopez, A.J., Baars, J.W., Hack, C.E., & van Oers, M.H. (2001). Complement activation plays a key role in the side-effects of rituximab treatment. <i>British Journal of Haematology, 115</i>, 807-811.
Weiner, L.M. (1999). Monoclonal antibody therapy of cancer. <i>Seminars in Oncology, 26</i>(5, Suppl. 14), 43-51.
Wing, M.G., Moreau, T., Greenwood, J., Smith, R.M., Hale, G., Isaacs, J., et al. (1996). Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: Involvement of CD16 (FcγRIII) and CD11a/CD18 (LFA-1) on NK cells. <i>Journal of Clinical Investigation, 98</i>, 2819-2826.
Winkler, U., Jensen, M., Manzke, O., Schulz, H., Diehl, V., & Engert, A. (1999). Cytokine-release syndrome in patients with B-cell chronic lymphocytic leukemia and high lymphocyte counts after treatment with an anti-CD20 monoclonal antibody (rituximab, Idec-C2B8). <i>Blood, 94</i>, 2217-2224.
Wood, A.M. (2001). Rituximab: An innovative therapy for non-Hodgkin's lymphoma. <i>American Journal of Health-System Pharmacy, 58</i>, 215-229.
Yeung, S.-C.J., & Escalante, C.P. (2006). Oncologic emergencies. In D.W. Kufe, R.C. Bast, Jr., W.N. Hait, W.K. Hong, R.E. Pollock, R.R. Weichselbaum, et al. (Eds.), <i>Cancer medicine</i> (7th ed., pp. 2246-2265). Hamilton, Canada: B.C. Decker.