The impact of granulocyte colony stimulating factor on patients receiving chimeric antigen receptor <scp>T</scp> ‐cell therapy

Infectious complications following immunosuppressive therapy increase morbidity and mortality in patients combatting malignancy.1 The inverse relationship between circulating leukocyte levels infection potential places with prolonged profound neutropenia at greatest risk.2 Granulocyte colony stimulating factor (GCSF) after aggressive chemotherapy is a supportive measure recommended to reduce intensity ultimately abrogate infection. Chimeric antigen receptor T-cell (CAR-T) represents major advancement the management of refractory or relapsed malignancies.3 Patients receiving CAR-T have multiple factors that impair their immunity risk.4 theoretical for GCSF exacerbate cytokine release syndrome (CRS) prompted guidelines recommend against administering within 14 days infusion.5 However, few studies exist characterize outcomes ultimate impact concurrent remains unknown.6 Our primary objective was comparison neutrophil kinetics who did not receive axicabtagene ciloleucel. Secondary included comparing therapy-related toxicity characteristics rates. This Mayo Foundation Institutional Review Board approved retrospective analysis evaluated consecutive, adult cancer received commercial ciloleucel January 2018 December 2020. actively participating clinical trial, considered vulnerable population, refusing research participation were excluded. All provided written informed consent had them by legal power attorney prior data collection. electronic health record (EHR) compiled utilizing standardized form developed investigators. Baseline criteria established immediately lymphodepleting chemotherapy. Lymphoma diagnosis subtyping reported according World Health Organization classification criteria.7 Relevant laboratory values, medications, microbiology abstracted from time infusion through disease relapse, death, maximum 100 infusion. Neutropenia severe defined as an absolute cell (ANC) count below 0.5 × 109 cells/L 0.1 cells/L, respectively.1 ANC recovery occurred when exceeded stayed above cells two consecutive days. Also, originally prescribed administered throughout period until recovery. In April 2019, our institutional cellular practice committee changed ANC-based administration, where prescribing discontinued measured infection-based indication reserved presenting febrile increased concern thorough evaluation. Both CRS Immune effector cell-associated neurotoxicity (ICANS) events graded published criteria.8 An infectious episode any positive culture site. Catheter-related infections accordance previously guidelines. oral candidiasis based on examination symptom assessment. Invasive fungal viral met consensus definitions methods detection. patient values summarized counts percentages categorical variables, medians interquartile ranges (IQR) continuous variables. Distribution baseline variables use assessed t tests, Kruskal-Wallis, chi-square test, Fisher Exact Test appropriate. Kaplan-Maier estimation used calculate cumulative incidence 95% confidence interval. Univariate Cox proportional hazard models, dependent covariates appropriate, demonstrate association independent outcomes. Analyses conducted using R (Version 3.6.3, Statistical Computing, Vienna, Austria). Note, p less than 0.05 statistically significant. 70 median age 59.4 (44.3, 63.9) years beginning lymphodepletion, 45 (64%) male, 63 (90%) Caucasian. A diffuse large B-cell lymphoma most common (n = 44, 64%) transformed follicular second 14, 20%). parameters similar groups exception body surface area (BSA) which greater (2.0 vs. 1.9, 0.04). Lymphodepletion universally cyclophosphamide 500 mg/m2 fludarabine 30 mg/m2. Median duration follow up CAR 5.3 (3.8, 12.7) months 22 still remission day post There 32 April, 2019 38 change GCSF. Thirty (94%) five (13%) implemented. protocol before change. With too provide meaningful analysis, we report results simply use. So, 35 (50%) eight (IQR: 6, 13) doses dosage 3840 mcg 1920–6120) first dose 3 1, 4.4) significantly fewer total (6.5 10, 0.05) (4.5 9, < 0.01) (4 0.20) reduced 5, 0.06). Additional neutropenia-related outcome details are presented Table 1. compared those without use, 86% versus 88%, respectively. no significant difference severity (median grade: 2 2); however, longer GCSF, 8 4.5 (p 0.01), Additionally, incidence, severity, ICANS groups. particularly tocilizumab corticosteroids, Further information toxicity-related lower overall risk (HR 0.80, CI: 0.41–1.59, 0.53) bacterial (HR: 0.61, 0.24–1.57, 0.30) use; but these (Figure S1). cohort axi-cel treatment rates grade slightly higher previous studies; this may reflect differences trial enrollment real-world population.3 Interestingly, more likely experience neutropenic episodes; during reduced. Unfortunately, raises possibility optimal discontinuing support well concordant other evidence demonstrating related GCSF.6 Notably, significance finding unknown corticosteroids associated Risk initiation although non-significant possibly due small sample size. Ultimately, believe reasonable population benefit timing requires further investigation. publication supported CTSA Grant Number UL1 TR002377 National Center Advancing Translational Science (NCATS). Its contents solely responsibility authors do necessarily represent official views NIH. specific grant funding agencies public, commercial, not-for-profit sectors. Dr. N. Nora Bennani: Has participated advisory boards Purdue Pharma, Verastem Oncology, Acrotech Biopharma, Sea Gen, Inc. Yi Lin: served consultant Kite/Gilead, Celgene, JUNO, Bluebird Bio, Janssen, Legend BioTech, Gamida Cells, Novartis, Merck, Takeda. board Sorrento: Data Safety Monitoring (DSMB). Jason Barreto concept design, collection, interpretation, manuscript creation involving critical writing revising intellectual content. Radhika Bansal Matthew A. Hathcock Corina J. Doleski Justin R. Hayne Tuan Truong Adrienne Nedved Stephen M. Ansell Bennani Jonas Paludo Jose C. Villasboas Lin contributed equally w/ Johnston co-senior authors. Patrick B. deidentified findings study available request corresponding author. publicly privacy ethical restrictions. Figure S1. Cumulative (A). (B) Please note: publisher responsible content functionality supporting supplied Any queries (other missing content) should be directed author article.