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Critical Care |

Cytokine Release Syndrome After CAR-T Cell Infusion: Successful Treatment With Interleukin-6 Receptor Inhibitor and Corticosteroids

Anil Singh, MD; Stephen Pastores, MD; Kaye Hale, MD; Louis Voigt, MD; Neil Halpern, MD
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Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY


Chest. 2014;146(4_MeetingAbstracts):272A. doi:10.1378/chest.1994875
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Abstract

SESSION TITLE: Critical Care Cases I

SESSION TYPE: Affiliate Case Report Slide

PRESENTED ON: Monday, October 27, 2014 at 11:00 AM - 12:00 PM

INTRODUCTION: Immunotherapy with chimeric antigen receptor (CAR)-engineered T cells is a promising new treatment for acute lymphoblastic leukemia (ALL), CLL, and lymphomas. We report a case of cytokine release syndrome (CRS) after CAR-T cell infusion requiring ICU admission.

CASE PRESENTATION: A 58-year old male developed B-cell ALL and received 5-drug chemotherapy with complete remission. 19 months later, he underwent allogeneic HSCT complicated by mild GVHD. BM biopsy 5 months later revealed hypercellular marrow with 81% blasts. CSF cytology was negative; he received intrathecal cytarabine complicated by a seizure and was maintained on levetiracetam. He was admitted to the hospital and 48 h after receiving cyclophosphamide, he was given an infusion of CAR-T cells. 6 days post-infusion, he developed respiratory failure, hypotension and high-grade fevers. Lab data showed WBC 0.1, hemoglobin 7.3, platelets 10,000; D-dimer 388, fibrinogen 401, LDH 215; lactate 2.8; CRP 10.9; coagulation, renal, and liver function tests were unremarkable. CXR showed new patchy RLL opacity. He required intubation and vasopressors and was admitted to the ICU. He was treated with blood products, allopurinol, G-CSF, and antimicrobials for suspected neutropenic sepsis; all cultures were negative except for VRE colonization in stool. CRS was considered and he received tocilizumab (IL-6 receptor inhibitor) and corticosteroids concomitantly. Within 48 h, defervescence occurred and he was weaned off vasopressors and extubated. He was discharged to the ward on ICU day 7. The absolute neutropenia resolved. BM aspirate 4 days post-ICU discharge showed no evidence of leukemia.

DISCUSSION: CRS is caused by an exaggerated systemic immune response mediated by T cells, B cells, NK cells and monocytes/macrophages which release inflammatory cytokines (IL-6, IL-10, interferon-gamma) resulting in endothelial and organ damage that can be fatal. CRS usually occurs between 6-20 days after T cell infusion. Clinical severity is directly related to the degree of cytokine elevation after the infusion and is characterized by persistent fevers, hypotension, and respiratory distress in the absence of documented sepsis.

CONCLUSIONS: Critical care practitioners should be aware of the possibility of CRS in patients receiving CAR-T cells. Timely and active anti-cytokine and corticosteroid therapy can be life-saving in these patients.

Reference #1: Grupp SA, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 2013;368:1509-18.

DISCLOSURE: The following authors have nothing to disclose: Anil Singh, Stephen Pastores, Kaye Hale, Louis Voigt, Neil Halpern

No Product/Research Disclosure Information


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