scholarly journals Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline

2021 ◽  
Author(s):  
Bianca D. Santomasso ◽  
Loretta J. Nastoupil ◽  
Sherry Adkins ◽  
Christina Lacchetti ◽  
Bryan J. Schneider ◽  
...  
Keyword(s):  
T Cell ◽  
Supportive Care ◽  
Effector Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T

PURPOSE To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy. METHODS A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021. RESULTS The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus. RECOMMENDATIONS The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell–related toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell–associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell–associated neurotoxicity syndrome should be managed with corticosteroids and supportive care. Additional information is available at www.asco.org/supportive-care-guidelines .

scholarly journals Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS)

2022 ◽  
Vol 10 (1) ◽  
pp. e003847
Author(s):  
Marc Wehrli ◽  
Kathleen Gallagher ◽  
Yi-Bin Chen ◽  
Mark B Leick ◽  
Steven L McAfee ◽  
...  
Keyword(s):  
T Cell ◽  
Effector Cell ◽  
Standard Treatment ◽  
Treatment Guidelines ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T ◽  
Steroid Refractory

In addition to remarkable antitumor activity, chimeric antigen receptor (CAR) T-cell therapy is associated with acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Current treatment guidelines for CRS and ICANS include use of tocilizumab, a monoclonal antibody that blocks the interleukin (IL)-6 receptor, and corticosteroids. In patients with refractory CRS, use of several other agents as third-line therapy (including siltuximab, ruxolitinib, anakinra, dasatinib, and cyclophosphamide) has been reported on an anecdotal basis. At our institution, anakinra has become the standard treatment for the management of steroid-refractory ICANS with or without CRS, based on recent animal data demonstrating the role of IL-1 in the pathogenesis of ICANS/CRS. Here, we retrospectively analyzed clinical and laboratory parameters, including serum cytokines, in 14 patients at our center treated with anakinra for steroid-refractory ICANS with or without CRS after standard treatment with tisagenlecleucel (Kymriah) or axicabtagene ciloleucel (Yescarta) CD19-targeting CAR T. We observed statistically significant and rapid reductions in fever, inflammatory cytokines, and biomarkers associated with ICANS/CRS after anakinra treatment. With three daily subcutaneous doses, anakinra did not have a clear, clinically dramatic effect on neurotoxicity, and its use did not result in rapid tapering of corticosteroids; although neutropenia and thrombocytopenia were common at the time of anakinra dosing, there were no clear delays in hematopoietic recovery or infections that were directly attributable to anakinra. Anakinra may be useful adjunct to steroids and tocilizumab in the management of CRS and/or steroid-refractory ICANs resulting from CAR T-cell therapies, but prospective studies are needed to determine its efficacy in these settings.

scholarly journals How I treat adverse effects of CAR-T cell therapy

ESMO Open ◽  
2020 ◽  
Vol 4 (Suppl 4) ◽  
pp. e000746 ◽  
Author(s):  
Lucrecia Yáñez ◽  
Ana Alarcón ◽  
Miriam Sánchez-Escamilla ◽  
Miguel-Angel Perales
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Early Recognition ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigenreceptor (CAR) T cell therapy has demonstrated efficacy in B cell malignancies, particularly for acute lymphoblastic leukaemia (ALL) and non‑Hodgkin lymphomas. However, this regimen is not harmless and, in some patients, can lead to a multi organ failure. For this reason, the knowledge and the early recognition and management of the side effects related to CAR-T cell therapy for the staff is mandatory. In this review, we have summarised the current recommendations for the identification, gradation and management of the cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as infections, and related to CAR-T cell therapy.

scholarly journals Immune Effector Cell Associated Neurotoxicity (ICANS) in Pediatric and Young Adult Patients Following Chimeric Antigen Receptor (CAR) T-Cell Therapy: Can We Optimize Early Diagnosis?

2021 ◽  
Vol 11 ◽  
Author(s):  
Brandon Douglas Brown ◽  
Francesco Paolo Tambaro ◽  
Mira Kohorst ◽  
Linda Chi ◽  
Kris Michael Mahadeo ◽  
...  
Keyword(s):  
T Cell ◽  
Young Adult ◽  
Effector Cell ◽  
Adult Patients ◽  
Immune Effector Cell ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

The Cornell Assessment for Pediatric Delirium (CAPD) was first proposed by the Pediatric Acute Lung Injury and Sepsis Investigators Network-Stem Cell Transplantation and Cancer Immunotherapy Subgroup and MD Anderson CARTOX joint working committees, for detection of immune effector cell associated neurotoxicity (ICANS) in pediatric patients receiving chimeric antigen receptor (CAR) T-cell therapy. It was subsequently adopted by the American Society for Transplantation and Cellular Therapy. The utility of CAPD as a screening tool for early diagnosis of ICANS has not been fully characterized. We conducted a retrospective study of pediatric and young adult patients (n=15) receiving standard-of-care CAR T-cell products. Cytokine release syndrome (CRS) and ICANS occurred in 87% and 40% of patients, respectively. ICANS was associated with significantly higher peaks of serum ferritin. A change in CAPD from a prior baseline was noted in 60% of patients with ICANS, 24–72 h prior to diagnosis of ICANS. The median change from baseline to maximum CAPD score of patients who developed ICANS versus those who did not was 13 versus 3, respectively (p=0.0004). Changes in CAPD score from baseline may be the earliest indicator of ICANS among pediatric and young adult patients which may warrant closer monitoring, with more frequent CAPD assessments.

Nichts für Schönwetterkapitäne: CAR-T-Zellen – Immunonkologie trifft Intensivmedizin

2020 ◽  
Vol 41 (10) ◽  
pp. 673-679
Author(s):  
Jorge Garcia Borrega ◽  
Michael von Bergwelt-Baildon ◽  
Boris Böll
Keyword(s):  
Real World ◽  
Effector Cell ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Effector Cell ◽  
Immune Effector ◽  
Car T

Zusammenfassung CRS und ICANS als Nebenwirkung von CAR-T-Zellen Das Cytokine-Release-Syndrome (CRS) ist die häufigste Nebenwirkung einer CAR-T-Zell-Therapie und kann von leichtem Fieber bis zu einem Multiorganversagen führen. Pathophysiologisch kommt es beim CRS zu einem Zytokinsturm und trotz einer Therapie mit Tocilizumab sind refraktäre und tödliche Verläufe beschrieben. Die Symptome des Immune-Effector-Cell-associated-Neurotoxicity-Syndrome (ICANS) variieren von leichter Desorientiertheit bis zum lebensbedrohlichen Hirnödem. Die Pathophysiologie und Therapie des ICANS sind noch nicht ausreichend erforscht. Die Differenzialdiagnosen von CRS und ICANS sind komplex und umfassen neben Infektionen und Sepsis unter anderem auch eine Toxizität der vorhergehenden Therapie, ein Tumorlysesyndrom und nicht zuletzt einen Progress der Grunderkrankung. Ein klinischer oder laborchemischer Parameter zum sicheren Beweis oder Ausschluss eines CRS oder ICANS gibt es zum heutigen Zeitpunkt nicht. Intensivmedizinische Relevanz und potenzielle Entwicklungen der CAR-T-Zell-Therapie Erste Auswertungen von Real-world-Daten deuten auf eine höhere Rate an schweren Nebenwirkungen im Rahmen der CAR-T-Zell-Therapie als in den Zulassungsstudien hin. Für die Indikation r/r-DLBCL könnten schätzungsweise bis zu maximal 300 Patienten pro Jahr in Deutschland eine intensivmedizinische Betreuung im Rahmen der CAR-T-Zell-Therapie benötigen. Studien mit wesentlich häufigeren soliden Tumoren könnten die Patientenzahl drastisch erhöhen. Therapieziel bei CAR-T-Zell-Patienten und Entscheidungen bei Therapiezieländerung Aufgrund des neuen Therapiekonzepts kann ein Konflikt zwischen bislang palliativem Patientenkollektiv und nun möglicherweise langfristigen Remissionen entstehen. Eine frühzeitige Aufklärung über potenziell lebensbedrohliche Nebenwirkungen im Rahmen der Therapie und eine interdisziplinäre Besprechung der Therapieziele mit den Patienten ist entscheidend.

scholarly journals Clinical Presentation, Management and Biomarkers of Cytokine Release Syndrome after Anti-CD19 CART-Cell Therapy for r/r ALL

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5625-5625
Author(s):  
Ping Li ◽  
Lili Zhou ◽  
Shiguang Ye ◽  
Shaoguang Li ◽  
Aibin Liang
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Clinical Presentation ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a novel treatment modality for B-cell malignancies. CD19-specific CAR-T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL). However, cytokine release syndrome (CRS) is the most common and severe toxicities of CAR T-cell therapy for ALL, and clinical experience is limited. Here, we describe the clinical presentation and management of 30 patients who presented with CRS following CAR-T cell therapy for relapsed/refractory ALL at our hospital. 12 of the 30 patients (40%) developed grade 1-2 CRS, 14 patients (46.7%) presented with grade 3-4 CRS and 2 patients (6.7%) died of grade 5 CRS. Compared with grade 1-2 CRS, grade 3-4 CRS correlated negatively with overall survival and progression-free survival (P =0.02). We found that higher ferritin levels and percentages of CD19 positive cells in blood lymphocytes cells at time of CAR-T cell infusion were associated with more severe CRS. Grade 3-4 neurotoxicity was frequently present in patients with grade ≧3 CRS. We also observed that the organ disfunctions occurred in sequence after fever onset during the period of CRS. Neurotoxicity, cardiovascular disfunction and cytopenia in some patients manifest as biphasic. Compared to use of tocilizumab for CRS ≧ grade 3, early intervention of tocilizumab for hyperpyrexia duration ≧ 6h alleviates the severity of CRS, and no patients died of severe CRS since this management approach was performed. As use of novel CAR-T cell therapy expands, the data from our clinical experience may help others anticipated the clinical course of organ function and manage CRS in CAR-T therapy. Figure Disclosures No relevant conflicts of interest to declare.

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