{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:15:44Z","timestamp":1790043344130,"version":"4.0.1"},"reference-count":25,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"corresponding author"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Cytokine release syndrome (CRS) is a life-threatening systemic inflammatory condition marked by excessive cytokine production, leading to multi-organ dysfunction. It is commonly associated with T-cell-engaging therapies such as chimeric antigen receptor (CAR) T cells, T-cell receptor bispecific molecules, and monoclonal antibodies. Carfilzomib, a proteasome inhibitor, is known to cause a range of adverse effects, primarily hematologic and cardiovascular. However, multiorgan failure grade 5 (fatal), resembling CRS has not been previously reported in association with Carfilzomib. Case Report: A 74-year-old male with relapsed multiple myeloma developed grade 5 multiorgan failure 60 min after the third dose of Carfilzomib, resulting in death within 24 h of symptom onset. The patient tolerated the first doses of Carfilzomib well with only fever and headache developing post infusion. Before the second dose, the patient developed worsening pancytopenia, prompting the discontinuation of Lenalidomide. After the second Carfilzomib infusion, he experienced fever and transient encephalopathy, which resolved with acetaminophen, corticosteroids, and supportive care. However, following the third dose, he rapidly deteriorated\u2014developing fever, tachycardia, hypotension, hypoxia, and encephalopathy. Despite aggressive management with intravenous fluids, broad-spectrum antibiotics, corticosteroids, and tocilizumab, the patient progressed to refractory shock and multi-organ failure, culminating in death within 24 h. A comprehensive infectious workup was negative, ruling out sepsis and suggesting possible Carfilzomib-induced CRS. Conclusion: Grade 5 multiorgan failure with signs and symptoms similar with CRS following Carfilzomib administration is a rare but potentially fatal adverse drug reaction. Further research is needed to better define the risk factors and optimal management strategies for Carfilzomib-induced multiorgan failure and possible CRS.<\/jats:p>","DOI":"10.3390\/jcm14134723","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T09:57:39Z","timestamp":1751536659000},"page":"4723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Multiorgan Failure Resembling Grade 5 (Fatal) Cytokine Release Syndrome in Patient with Multiple Myeloma Following Carfilzomib Infusion: A Case Report"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7260-5061","authenticated-orcid":false,"given":"Strahinja","family":"Gligorevic","sequence":"first","affiliation":[{"name":"Internal Medicine Residency Program, North Central Bronx Hospital, Bronx, NY 10467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3581-3584","authenticated-orcid":false,"given":"Nebojsa","family":"Brezic","sequence":"additional","affiliation":[{"name":"Internal Medicine Residency Program (Preliminary Track), Lincoln Medical and Mental Health Center, Bronx, NY 10467, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Jagodzinski","sequence":"additional","affiliation":[{"name":"Hospital Medicine Fellowship, Mayo Clinic Health System, Eau Claire, WI 54703, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andjela","family":"Radulovic","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Novi Sad, Novi Sad 400111, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Peranovic","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Novi Sad, Novi Sad 400111, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-8812","authenticated-orcid":false,"given":"Igor","family":"Dumic","sequence":"additional","affiliation":[{"name":"Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54703, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/PPO.0000000000000515","article-title":"Cytokine Release Syndrome Biology and Management","volume":"27","author":"Cobb","year":"2021","journal-title":"Cancer J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Subklewe","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1200\/JCO.22.01365","article-title":"Idecabtagene Vicleucel for Relapsed\/Refractory Multiple Myeloma: Real-World Experience from the Myeloma CAR T Consortium","volume":"41","author":"Hansen","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9531","DOI":"10.1200\/JCO.2021.39.15_suppl.9531","article-title":"Characterization of cytokine release syndrome (CRS) following treatment with tebentafusp in patients (pts) with previously treated (2L+) metastatic uveal melanoma (mUM)","volume":"39","author":"Carvajal","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_5","first-page":"87","article-title":"Incidence and management of adverse events in patients with relapsed and\/or refractory multiple myeloma receiving single-agent carfilzomib","volume":"6","author":"Harvey","year":"2014","journal-title":"Clin. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"67A","DOI":"10.1378\/chest.1782952","article-title":"A Case of \u2018Carfilzomib\u2019 Induced Flash Pulmonary Edema","volume":"145","author":"Chadha","year":"2014","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ytab076","DOI":"10.1093\/ehjcr\/ytab076","article-title":"Proteasome inhibitor-induced coronary vasospasm in multiple myeloma: A case report","volume":"5","author":"Mikhail","year":"2021","journal-title":"Eur. Heart J. Case Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jccase.2024.07.006","article-title":"Carfilzomib-induced pulmonary hypertension in a patient with multiple myeloma","volume":"30","author":"Uruno","year":"2024","journal-title":"J. Cardiol. Cases"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2050313X21994031","DOI":"10.1177\/2050313X21994031","article-title":"Carfilzomib-induced pulmonary hypertension with associated right ventricular dysfunction: A case report","volume":"9","author":"McGregor","year":"2021","journal-title":"SAGE Open Med. Case Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1177\/10781552231190039","article-title":"Carfilzomib-induced life-threatening lung injury in refractory multiple myeloma","volume":"29","author":"Ghasoub","year":"2023","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1177\/10781552211067433","article-title":"Carfilzomib-induced thrombotic microangiopathy. A case report","volume":"28","author":"Scheggi","year":"2022","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e2163","DOI":"10.1002\/cnr2.2163","article-title":"Carfilzomib-Induced Thrombotic Microangiopathy -Two Case Reports","volume":"7","author":"Attucci","year":"2024","journal-title":"Cancer Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"286","DOI":"10.52964\/AMJA.0880","article-title":"Fatal pulmonary toxicity following Carfilzomib administration","volume":"20","author":"Marschall","year":"2021","journal-title":"Acute Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lazaro Sanchez, A.D., Benitez Fuentes, J.D., Gil, G.L., Garc\u00eda, M.T., Moreno, E.F., Zamora, P.C., Yago, J.B., Mohamed, K.M., and Arroyo Rodr\u00edguez, A.B. (2025). Clinical and Proteomic Insights into a Cytokine Release Syndrome Triggered by Tebentafusp in a Metastatic Uveal Melanoma Patient: Case Report. J. Clin. Med., 14.","DOI":"10.3390\/jcm14041333"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1182\/asheducation-2016.1.567","article-title":"Cytokine release syndrome with novel therapeutics for acute lymphoblastic leukemia","volume":"2016","author":"Frey","year":"2016","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102922","DOI":"10.1016\/j.esmoop.2024.102922","article-title":"Management of infusion-related reactions in cancer therapy: Strategies and challenges","volume":"9","author":"Barroso","year":"2024","journal-title":"ESMO Open"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1177\/1078155220967738","article-title":"A multicenter review of infusion-related reactions to daratumumab for relapsed multiple myeloma in the real world setting","volume":"27","author":"Geirnaert","year":"2021","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.idc.2022.07.001","article-title":"Cytokine Release Syndrome and Sepsis: Analogous Clinical Syndromes with Distinct Causes and Challenges in Management","volume":"36","author":"Athale","year":"2022","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/MOP.0000000000000043","article-title":"Toxicity management for patients receiving novel T-cell engaging therapies","volume":"26","author":"Barrett","year":"2014","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Slaats, J., Ten Oever, J., van de Veerdonk, F.L., and Netea, M.G. (2016). IL-1\u03b2\/IL-6\/CRP and IL-18\/ferritin: Distinct Inflammatory Programs in Infections. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005973"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sterner, R.C., and Sterner, R.M. (2022). Immune effector cell associated neurotoxicity syndrome in chimeric antigen receptor-T cell therapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.879608"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gust, J., Ponce, R., Liles, W.C., Garden, G.A., and Turtle, C.J. (2020). Cytokines in CAR T Cell-Associated Neurotoxicity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.577027"},{"key":"ref_24","first-page":"705","article-title":"Spotlight on Tocilizumab in the Treatment of CAR-T-Cell-Induced Cytokine Release Syndrome: Clinical Evidence to Date","volume":"16","author":"Si","year":"2020","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s40264-018-0760-1","article-title":"Benefit-Risk Assessment of Blinatumomab in the Treatment of Relapsed\/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia","volume":"42","author":"Stein","year":"2019","journal-title":"Drug Saf."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4723\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:06Z","timestamp":1760033046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/13\/4723"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,3]]},"references-count":25,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["jcm14134723"],"URL":"https:\/\/doi.org\/10.3390\/jcm14134723","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,3]]}}}