Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement

2021 ◽  
Author(s):  
Matteo Di Nardo ◽  
Ali H Ahmad ◽  
Pietro Merli ◽  
Matthew S Zinter ◽  
Leslie E Lehman ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Extracorporeal Membrane Oxygenation ◽  
Cell Transplantation ◽  
Effector Cell ◽  
Consensus Statement ◽  
Immune Effector Cell ◽  
Immune Effector ◽  
Membrane Oxygenation ◽  
Haematopoietic Cell

The impact of early versus late tocilizumab administration in patients with cytokine release syndrome secondary to immune effector cell therapy

2021 ◽  
pp. 107815522110526
Author(s):  
Rachel Peaytt ◽  
Laura Beth Parsons ◽  
Darby Siler ◽  
Rachel Matthews ◽  
Belinda Li ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Interleukin 6 ◽  
Effector Cell ◽  
Negative Consequences ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Immune Effector Cell ◽  
Immune Effector ◽  
Fever Onset ◽  
The Impact

Introduction Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity. Optimizing the timing of tocilizumab could avoid glucocorticoid use and improve outcomes. This study assesses tocilizumab timing on patient outcomes and healthcare resource utilization. Methods This is a retrospective single-institution analysis of 28 patients who received tocilizumab for cytokine release syndrome secondary to immune effector cell therapy. Patients were categorized into two groups: Early Tocilizumab (within 24 h) or Late Tocilizumab groups (more than 24 h) from fever onset. The composite primary endpoint was glucocorticoid use, intensive care unit admission, or inpatient mortality. Secondary outcomes include comparing the various presentations of cytokine release syndrome, need for vasopressors, length of stay, rates of neurotoxicity, and C-reactive protein and ferritin trends. Results The Early Tocilizumab group presented with more rapid fever onset (35 vs.113 h, P = 0.017) and higher maximum cytokine release syndrome grade (Median, Grade 2 vs. Grade 1, P = 0.025). Additionally, the Early Tocilizumab group required more doses of tocilizumab (Median, 2 vs. 1, P = 0.037). Despite the difference in cytokine release syndrome presentation, the primary composite endpoint was not statistically different between groups. Conclusion Earlier onset of fever appears to be associated with more severe, progressive cytokine release syndrome requiring multiple doses of anti-interleukin-6 therapy. Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome.

scholarly journals NCMP-24. PRE-INFUSION NEUROFILAMENT LIGHT CHAIN (NFL) LEVELS PREDICT THE DEVELOPMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME (ICANS)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii127-ii128
Author(s):  
Omar Butt ◽  
Alice Zhou ◽  
Suzanne Schindler ◽  
Anne Fagan ◽  
John Dipersio ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Light Chain ◽  
Effector Cell ◽  
Immune Effector Cell ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell Therapy ◽  
Car T

Abstract Neurological side effects after chimeric antigen receptor-modified (CAR) T cell therapy are common and potentially devastating. Termed immune effector cell-associated neurotoxicity syndrome (ICANS), symptoms range from mild encephalopathy to diffuse cerebral edema. No predictive biomarkers exist to identify individuals at risk for developing ICANS. Serum neurofilament light chain (NfL) is a well-established marker of neural injury known to dynamically change in neuro-inflammatory disorders (e.g. multiple sclerosis). We hypothesized individuals undergoing CAR T cell therapy who ultimately developed ICANS would have early and sustained elevations in serum NfL. We performed a retrospective analysis of serum samples from 11 individuals treated with tisagenlecleucel or axicabtagene ciloleucel (mean age 61.3, 18% female, 27% ICANS, all with peak severity score 3). Most individuals had a longitudinal sampling at baseline, pre-infusion, post-transfusion day (PTD) 1, PTD 3, PTD 7, PTD 14, and PTD 30. Serum NfL were assayed using a Simoa HD-1/HD-X kit (QuanterixTM). We found that individuals who developed ICANS had early and sustained elevations in serum NfL levels at baseline (p = 0.0075), pre-infusion (p = 0.0172), and PTD 3 (p = 0.0026) and PTD 30 (p = 0.0066). All group comparisons survived multiple comparison testing using false-discovery rate (FDR). Receiver operating characteristic (ROC) curve classification by logistic regression of serum NfL revealed an area under the curve (AUC) of 1.0 with a cut-off of 44 pg/mL. No correlation was observed between NfL levels and age, sex, or history of central nervous system involvement of the underlying malignancy. In summary, we found serum NfL levels are a robust, early marker for the development of ICANS. Our findings suggest the risk of developing ICANS reflects pre-transfusion host-factors, permitting the screening well in advance of drug administration.

Sign in / Sign up

Export Citation Format

Share Document