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Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.

About 70% of patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel) and who achieve a partial response (PR) or stable disease (SD) on the day 30 (D30) positron emission tomography (PET)–computed tomography (CT) scan progress; however, the factors that are predictive of progression are unknown. This a retrospective study of patients with LBCL who were treated with axi-cel at MD Anderson Cancer Center between January of 2018 and February of 2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to a complete response (CR). Among 95 patients with a D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day −5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (P = .05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was a lower maximum standardized uptake volume (SUVmax; P < .001); all patients with D30 SUVmax ≥ 10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed between patients who converted from D30 PR/SD to subsequent CR and those who had been in CR since D30 (P = .19). Novel predictive and prognostic markers based on tissue biopsy and noninvasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

Corticosteroids are used to treat the acute complications of chimeric antigen receptor (CAR) T-cell therapy. Strati et al examine the impact of corticosteroids on patient outcomes following CAR T-cell therapy for large B-cell lymphoma. Use of higher doses of steroids is associated with shorter progression-free survival at 10 months and decreased overall survival., Key Points Higher cumulative dose of corticosteroids is associated with early progression after CAR-T therapy in large B-cell lymphoma.Higher cumulative dose and prolonged, early corticosteroid use is associated with shorter overall survival after CAR-T therapy., Visual Abstract, Corticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities.

The impact of bridging therapy (BT) administered between leukapheresis and chimeric antigen receptor (CAR) T-cell therapy for large B-cell lymphoma (LBCL) is unclear. We evaluated the influence of BT (systemic therapy [ST], radiation therapy [RT], or combined-modality therapy [CMT]) on outcomes of 148 LBCL patients who underwent leukapheresis for planned axicabtagene ciloleucel (axi-cel) infusion. The 55% (n = 81) of patients who received BT were more likely to have international prognostic index (IPI) score ≥3 (P ≤ .01), bulky disease (P = .01), and elevated lactate dehydrogenase (LDH; P ≤ .01). The 1-year progression-free (PFS) and overall survival (OS) rates were 40% and 65% in non-BT patients vs 21% and 48% in BT patients (P = .01 and .05, respectively). Twenty-four patients (16%) did not receive axi-cel, most commonly because of lymphoma progression (88%), despite 80% (n = 19) receiving BT. Among 124 patients who received axi-cel, 50% (n = 62) received BT with ST (n = 45), RT (n = 11), or CMT (n = 6); 1-year PFS and OS rates were not significantly different between BT and non-BT cohorts (P = .06 and .21, respectively). There was no difference in proportion of patients with IPI ≥3, limited-stage disease, or elevated LDH between ST, RT, and CMT groups. Compared with non-BT patients, 1-year PFS was inferior for ST-bridged patients (P = .01). RT-bridged patients had improved PFS compared with ST-bridged patients (P = .05). Despite the poor prognosis associated with requiring BT, RT can be an effective bridging strategy. Future studies are necessary to identify strategies that may improve access to CAR T-cell therapy and outcomes.

Introduction. Suboptimal CAR T-cell stimulation, expansion, and persistence is of theoretical concern in absence of CD19+ tumor B-cells. Adequate CAR T-cell expansion has been reported in the JULIET study among 7 relapsed or refractory (r/r) large B-cell lymphoma (LBCL) patients who had achieved complete metabolic remission (CMR) before tisagenlecleucel (tisa-cel) infusion. As patients in CMR at time of infusion were excluded from the ZUMA-1 trial, the efficacy of axicabtagene ciloleucel (axi-cel), whose construct and kinetics differ significantly from those of tisa-cel, remains unknown in this population. Methods. This is a retrospective study of all patients with r/r LBCL treated with standard of care (SOC) axi-cel at MD Anderson Cancer Center between 01/2018 and 02/2021 (data cut-off 04/2021). CMR was defined as a Deauville score Results. Two-hundred and six patients with R/R LBCL received SOC axi-cel between 01/2018 and 02/2021. Of these, 162 had a PET-CT scan performed after bridging therapy and before LDC, 10 of whom were in CMR at time of axi-cel infusion. The immediate treatment before achievement of CMR consisted of chemoimmunotherapy in 5 patients (platinum-based in 4 patients, methotrexate-based in 1 patient), radiation therapy in 3 patients, and biological therapy in 2 patients (lenalidomide and rituximab in 1 patient, and ibrutinib in 1 patient). When comparing the 152 patients with metabolically active disease to the 10 patients without, patients with active disease had more frequently at baseline (day -5) an international prognostic index score >= 3 (58% vs 10%, p=0.006), elevated lactate dehydrogenase (LDH)(70% vs 10%, p Interestingly, when comparing patients with active disease to those without, no difference for CRS of any grade (94% vs 90%, p=0.48), grade 3-4 CRS (8% vs 10%, p=0.58), ICANS of any grade (61% vs 70%, p=0.74) or grade 3-4 ICANS (38% vs 40%, p=1) was observed (Figure A). After a median follow-up of 12 months (95% CI, 11-13 months), 87 (54%) patients progressed and/or died, and median progression-free survival (PFS) was 6 months (95% CI, 2-10 months). Median PFS was significantly longer for patients without metabolically active disease at the time of axi-cel infusion (not reached vs 5 months, p=0.04) with a 1-year PFS rate of 80% as compared to 45% (Figure B). At most recent follow-up, 57 (35%) patients died, and median overall (OS) was not reached. One-year OS rate was higher for patients without metabolically active disease at baseline (80% vs 64%), but not statistically significant (p=0.23)(Figure C). Conclusions. Our data support the use of axi-cel in r/r LBCL patients who achieve a CMR before axi-cel infusion, warranting further investigation of its activity as consolidative strategy in future trials. Identification of effective and biologically rational bridging therapies aimed at decreasing disease burden and continue to improve outcomes in patients treated with axi-cel is needed. CAR T-cell amplification data by qPCR and pre-infusion levels of CD19+ non-tumoral B-cells in peripheral blood are being analyzed and will be presented at the conference. Figure 1 Figure 1. Disclosures Westin: Genentech: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Umoja: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Morphosys: Research Funding; 47 Inc: Research Funding. Steiner: Rafael Pharmaceuticals: Research Funding; Seattle Genetics: Research Funding; BMS: Research Funding. Parmar: Cellenkos Inc.: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Fowler: BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company; Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Flowers: Denovo: Consultancy; Burroughs Wellcome Fund: Research Funding; AbbVie: Consultancy, Research Funding; Acerta: Research Funding; Kite: Research Funding; Karyopharm: Consultancy; EMD: Research Funding; BeiGene: Consultancy; Takeda: Research Funding; Sanofi: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Genmab: Consultancy; Iovance: Research Funding; Allogene: Research Funding; TG Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; National Cancer Institute: Research Funding; Amgen: Research Funding; Cellectis: Research Funding; Nektar: Research Funding; Xencor: Research Funding; Spectrum: Consultancy; Ziopharm: Research Funding; Genentech/Roche: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy; Bayer: Consultancy, Research Funding; Morphosys: Research Funding; Biopharma: Consultancy; SeaGen: Consultancy; 4D: Research Funding; Janssen: Research Funding; Gilead: Consultancy, Research Funding; Epizyme, Inc.: Consultancy; Eastern Cooperative Oncology Group: Research Funding; Guardant: Research Funding; Adaptimmune: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Pharmacyclics: Research Funding. Ahmed: Xencor: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding. Nastoupil: Genentech: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Gilead/Kite: Honoraria, Research Funding; IGM Biosciences: Research Funding; Denovo Pharma: Other: DSMC; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; MorphoSys: Honoraria; Caribou Biosciences: Research Funding; ADC Therapeutics: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bayer: Honoraria. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Strati: Roche-Genentech: Consultancy; Astrazeneca-Acerta: Research Funding.

Background: About one third of patients with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) treated with autologous anti-CD19 CAR T-cell therapy achieve a partial response (PR) or a stable disease (SD) on day 30 (D30) PET-CT scan. Among these patients, only 30% will convert later to a complete response (CR), while 70% will eventually progress, experiencing significantly poor outcomes. Therefore, early identification of patients with D30 PR at risk for subsequent progression is of utmost importance and could allow for the development of novel consolidation strategies. Methods: This is a retrospective study of all patients with r/r LBCL treated with standard of care axicabtagene ciloleucel (axi-cel) at MD Anderson Cancer Center between 01/2018 and 02/2021 (data cut-off 04/2021). Clinical, laboratory and radiological characteristics were collected on day -5 and D30. All patients received lymphodepleting chemotherapy with cyclophosphamide and fludarabine. CRS and ICANS were prospectively graded according to CARTOX criteria from 01/2018 to 04/2019, and ASTCT criteria from 05/2019 onward. Response to treatment and progression were defined according to 2014 Lugano criteria. The association with categorical variables was evaluated using χ2 or Fisher exact tests, as appropriate. The difference in a continuous variable between patient groups was evaluated by the Mann-Whitney test. Results: By D30, 204 out of 206 patients were evaluable for response (2 were lost to follow-up). Among 204 evaluable patients, 102 (50%) achieved CR, 49 (24%) PR, 8 (4%) SD, and 45 (22%) progressive disease (PD)/death. Among the 57 patients who achieved PR/SD on the D30 PET-CT scan, 50 were evaluable for response at day 90 or beyond, and were included in the analysis, 5 were lost to follow-up, and 2 died of unrelated cause before restaging. Among the 50 patients with D30 PR/SD, 13 (26%) converted to CR on subsequent restaging, and 37 (74%) progressed and/or died of progressive disease. Among the 102 patients with D30 CR, 7 were lost to follow-up. In the remaining 95 evaluable patients, 72 (76%) remained in CR at day 90 restaging, and 13 (24%) progressed/died (Figure A). On univariate analysis, among baseline characteristics (day -5), including age, sex, performance status, international prognostic index score, laboratory values, SUV max, number of previous therapies, prior stem cell transplant, and use of bridging therapy, the only characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (median, 193 vs 128 X10 9/L, p=0.05); a trend for association with lower c-reactive protein was also observed (13.7 vs 36 mg/L, p=0.06). No difference in baseline characteristics was observed when comparing patients in CR since D30 to those with D30 PR who subsequently converted to CR. D30 laboratory, clinical and radiological characteristics were evaluated, and the only factor associated with conversion from D30 PR to subsequent CR was lower D30 SUV max (median 5.8 vs 9.8, p= 10 eventually progressing (Figure B). After a median follow-up of 12 months (95%CI, 11-13 months), no significant difference in median PFS was observed when comparing the 13 patients who converted from D30 PR/SD to subsequent CR to the 72 patients who had been in CR since D30 (1-year PFS rate, 100% vs 84%, p=0.19)(Figure C). No significant difference in median PFS was observed also in a landmark analysis at 90 days (p=0.19). Conclusions: Patients with D30 PR/SD subsequently converting to CR experience similar early outcomes as patients who achieved CR by D30. PET-associated parameters, such as SUV max of 10 or higher, may help identify patients with D30 PR/SD at risk of subsequent progression, who may benefit from clinical trials of consolidation therapy. Novel predictive and prognostic markers based on tissue biopsy for patients with D30 PR/SD and non-invasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease. Figure 1 Figure 1. Disclosures Westin: Umoja: Consultancy; ADC Therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Curis: Research Funding; Iksuda Therapeutics: Consultancy; Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; 47 Inc: Research Funding; Morphosys: Research Funding. Ahmed: Xencor: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seagen: Research Funding. Nastoupil: Denovo Pharma: Other: DSMC; Gilead/Kite: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Novartis: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; ADC Therapeutics: Honoraria; Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Genentech: Honoraria, Research Funding; IGM Biosciences: Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; MorphoSys: Honoraria. Steiner: Seattle Genetics: Research Funding; BMS: Research Funding; Rafael Pharmaceuticals: Research Funding. Flowers: Epizyme, Inc.: Consultancy; Acerta: Research Funding; Celgene: Consultancy, Research Funding; Denovo: Consultancy; Guardant: Research Funding; Cellectis: Research Funding; Pharmacyclics/Janssen: Consultancy; Iovance: Research Funding; Ziopharm: Research Funding; AbbVie: Consultancy, Research Funding; 4D: Research Funding; Biopharma: Consultancy; Janssen: Research Funding; Allogene: Research Funding; Novartis: Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; Genentech/Roche: Consultancy, Research Funding; Takeda: Research Funding; Nektar: Research Funding; Sanofi: Research Funding; Xencor: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Pfizer: Research Funding; Kite: Research Funding; TG Therapeutics: Research Funding; BeiGene: Consultancy; Bayer: Consultancy, Research Funding; EMD: Research Funding; Morphosys: Research Funding; Adaptimmune: Research Funding; Amgen: Research Funding; Genmab: Consultancy; SeaGen: Consultancy; Gilead: Consultancy, Research Funding; Spectrum: Consultancy; National Cancer Institute: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Pharmacyclics: Research Funding. Shpall: Novartis: Honoraria; Magenta: Honoraria; Magenta: Consultancy; Adaptimmune: Consultancy; Takeda: Patents & Royalties; Novartis: Consultancy; Affimed: Patents & Royalties; Navan: Consultancy; Axio: Consultancy; Bayer HealthCare Pharmaceuticals: Honoraria. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees. Strati: Roche-Genentech: Consultancy; Astrazeneca-Acerta: Research Funding.

Introduction. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common adverse effects of chimeric antigen receptor (CAR) T-cell therapy. Elevated biomarkers, such as ferritin and LDH, have been shown to correlate with more severe toxicity. The endothelial activation and stress index (EASIX) is a surrogate of endothelial activation, and correlates to other biomarkers of endothelial dysfunction. In allogeneic hematopoietic cell transplantation (HCT), it is predictive of toxicity such as fluid overload, which is correlative with endothelial dysfunction, as well as sinusoidal obstruction syndrome, non relapse mortality and overall survival (Luft et al, BMT 2019, Varma et al, BBMT, 2020, Jiang et al, Haematologica, 2020). In this study we describe the correlation of EASIX to CAR T cell related CRS and ICANS. Methods. Retrospective data from consecutive patients treated with standard of care axi-cel for non-Hodgkin's lymphoma at MD Anderson Cancer Center between January 2018 and April 2020 were included in the study. CRS and ICANS were graded according to CARTOX criteria (Neelapu et al, Nat Rev Clin Oncol, 2018), and after 5/2019, according to the ASTCT criteria (Lee et al, BBMT, 2019). EASIX parameters were recorded prior to lymphodepletion (the latest value on days -12 to -6) and were available for all 171 patients. The score was defined as lactate dehydrogenase (U/L) × creatinine (mg/dL)/ thrombocytes (10^9 cells per L), with LDH adjusted to the upper limit of normal. Predictors of toxicity were evaluated using Fine and Grey regression analysis considering death before grade 2-4 toxicity as a competing risk. Results. 171 consecutive patients treated with commercial axi-cel for diffuse large B cell lymphoma (n=133), transformed follicular lymphoma (n=28) and primary mediastinal lymphoma (n=10) were included in the study. Median age was 59 years (range, 18-85), and 120 (70%) were male. 151 patients had an ECOG performance status ≤1, 45 patients (26%) had a previous autologous HCT, and 3 (1.8%) had a previous allogeneic HCT. Prior to lymphodepletion, 96 (56%) patients had a high IPI score (≥3) and 134 (78%) were refractory to the previous line of treatment. With a median follow-up of 259 days (range: 25-800) since infusion, ICANS of any grade was noted in 109 (64%) patients, with 84 (49%) having grades 2-4. CRS of any grade was observed in 160 (93%) patients, with 81 (47%) having grades 2-4 CRS. A total of 56 (33%) patients were diagnosed with grade 2-4 ICANS and CRS. The median EASIX score for the entire cohort was 2.1 (range: 0.3-283; inter-quartiles: 1.1 and 4.6). On univariate analysis, EASIX levels above the median were associated with higher cumulative incidence (CI) of grade 2-4 ICANS (% CI: 61 vs 31%; HR=2.4, p Multivariate analysis showed EASIX score to be an independent predictor of grade 2-4 ICANS (HR=2.3, p=0.001) or CRS (HR=2.3, p=0.001); female gender of ICANS (HR=1.7, p=0.03) and lack of prior autologous transplant of CRS (HR=1.9, p=0.02). The impact of IPI did not reach statistical significance for either ICANS (HR=1.3, p=0.3) or CRS (HR=1.2, p=0.4). Further multivariate analysis for other biomarkers and their incorporation into a revised biomarker score will be presented at the meeting. Conclusions. Our results suggest that the EASIX score prior to lymphodepletion predicts higher grade CRS and ICANS in patients receiving axi-cel. These results of routinely available clinical variables require further prospective studies for validation, however our study shows that this score may better stratify patient risk of toxicity, and possibly inform clinical decisions and prevention strategies for patients at higher risk. Disclosures Nieto: Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Westin:47: Research Funding; Amgen: Consultancy; Morphosys: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Lee:Celgene: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Guidepoint Blogal: Consultancy; Aptitude Health: Speakers Bureau; Oncternal Therapeutics: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding. Nastoupil:Celgene: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gamida Cell: Honoraria; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Wang:Guidepoint Global: Consultancy; Dava Oncology: Honoraria; Verastem: Research Funding; Molecular Templates: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Nobel Insights: Consultancy; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; OncLive: Honoraria; InnoCare: Consultancy; Targeted Oncology: Honoraria; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding. Flowers:AbbVie: Consultancy, Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Bayer: Consultancy; National Cancer Institute: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy. Hawkins:Kite: Membership on an entity's Board of Directors or advisory committees. Rezvani:GemoAb: Membership on an entity's Board of Directors or advisory committees; Affimed: Other: Educational grant; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Other: Educational grant; Virogen: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing agreement; Formula Pharma: Membership on an entity's Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy. Shpall:Magenta: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees. Neelapu:Novartis: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Adicet Bio: Other; Calibr: Other; Unum Therapeutics: Other, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Karus Therapeutics: Research Funding; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; N/A: Other. Kebriaei:Jazz: Consultancy; Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board; Amgen: Other: Research Support.

Background Significant improvement in overall survival observed in patients on clinical trials and U.S. Food and Drug Administration approval of two chimeric antigen receptor (CAR) T-cell therapies have resulted in an increasing population of survivors who have undergone this therapy. Although adult survivors may experience similar physiologic and psychosocial sequelae to traditional cancer therapies, unique late effects and considerations are related to CAR T-cell therapy. Objectives This article reviews survivorship considerations, with particular attention paid to the physical, psychosocial, and financial effects for adults who have undergone CAR T-cell therapy. Methods A review of the physiologic and psychosocial sequelae resulting from CAR T-cell therapy is presented, with a focus on late effects and financial toxicities of treatment. Physiologic concerns include B-cell aplasia and resulting hypogammaglobulinemia, as well as prolonged cytopenias and associated risk for infection. Findings To date, adult CAR T-cell therapy survivorship data are limited. However, data from clinical trials suggest expected late effects from treatment. As this survivor population grows, research can identify physiologic and psychosocial needs unique to adult survivors and evaluate evidence-based interventions.

8057 Background: HLH is a rare but serious complication of chimeric antigen receptor (CAR) T cell therapy, characterized by severe immune activation, and immune mediated multi-organ failure. Diagnosis is difficult in the context of cytokine release syndrome (CRS) and optimal treatment and outcomes are unclear. Methods: Retrospective, descriptive analysis of patients with relapsed/refractory LBCL treated with SOC axi-cel at MD Anderson Cancer Center between 01/2018 - 10/2019 (data cut-off 12/21/2019). Progression-free survival (PFS) defined as time from axi-cel infusion to progression/death or last follow-up. Diagnosis of HLH per HLH-2004 and CART cell therapy toxicity guidelines (Neelapu, 2018) Results: One hundred and five patients with relapsed/refractory LBCL included, 6 diagnosed with HLH. No significant difference in baseline characteristics, disease stage, international prognostic index or inflammatory markers at baseline between groups, with exception of platelet count which was lower in HLH group 116 [37-129] versus 141 [9-391] (p = 0.07). Development of HLH was early after CART cell infusion at a median 11 days [7 – 78 days] with 3 patients having bone marrow hemophagocytosis; all 6 had abnormalities in liver function tests, fibrinogen, triglycerides, and at least 1 ferritin level > 10,000. CART toxicity in HLH cohort: 4 patients experienced grade 0-1 CRS, and 1 with grade 2 CRS while 3 HLH patients experienced grade 3-4 IEC-associated neurotoxicity syndrome ( ICANS), and 2 patients had grade 0-1 ICANS. Five HLH patients treated with high dose steroids, and tocilizumab; anakinra administered in 2 patients. Four of 6 patients had resolution of HLH with treatment and didn’t require escalation to HLH specific therapy however 1 patient was treated with steroids/etoposide. PFS and overall survival (OS) were significantly shorter in HLH group, PFS 1 months vs 8 months, respectively (p < 0.001) and median OS 2 months vs not reached, respectively (p = 0.001) follow up 10 months (95% CI 8-12 months). One patient died of acute respiratory failure, 2 patients died of HLH and multi-organ failure without progressive disease (PD). Of 3 remaining patients, all had radiographic PD at day 30, 2 of whom died of PD. Conclusions: HLH is likely an underreported complication of CART cell therapy, and patients with HLH have significantly worse outcomes. In this series the majority of patients died of PD, not the syndrome itself. More information is necessary to design treatment strategies that won’t compromise CART outcomes.

Introduction: Commercially available chimeric antigen receptor (CAR) T-cell therapy has improved the outcomes for patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma. Many pts have highly symptomatic, rapidly progressive disease that untreated could be fatal during the 3-4 week manufacturing interval. We examined the outcomes of pts treated with axicabtagene ciloleucel (axi-cel) and bridging interventions, including systemic therapy (ST) and radiation therapy (RT). Methods: We reviewed clinical efficacy and toxicity outcomes for 80 pts who underwent apheresis for axi-cel therapy between 12/2017 and 1/2019 at a single institution. Disease specific survival (DSS), progression free survival (PFS), toxicity free survival (TFS) and overall survival (OS) were defined from the date of CAR T-cell infusion. For the pts who received bridging treatment (defined as therapy given between apheresis and CAR T cell infusion), baseline clinical, treatment and toxicity characteristics were compared between cohorts that received ST versus RT. All comparisons were 2 sided. Results: Of the 80 pts who underwent apheresis, 73 (91%) received CAR T-cell therapy. Among these 73, 32 (44%) received bridging therapy and 41 (56%) did not. Pts who received bridging therapy were more likely to have an IPI of ≥3 at the time of apheresis (72%) compared to those that did not (39%; p=0.009). Of the 32 pts who received bridging therapy, 24 (75%) were treated with ST (corticosteroids [n=3], targeted therapy [n=4] and chemotherapy [n=17]) and 8 (25%) with RT. RT was administered to a median dose of 44.6 Gy (range 9-46 Gy) with a median fraction size of 2.5 Gy (range 1.8 -3 Gy). The median time between the end of RT and the CAR T-cell infusion was 16 days (range 0 -21). The median age of the entire bridging therapy cohort was 59 (range 24 - 85 years). Twenty five pts (78%) were male, 23 had DLBCL (72%). Comparing the ST (n=24) to the RT (n=8) cohort, there were no differences in ECOG PS ≥2 (p=0.296), IPI of ≥3 (p=0.654), double hit or triple hit status by IHC (p=0.378) or FISH (p=0.578), bulky disease (≥10 cm, p=1.0), or elevated LDH at the time of apheresis (p=1.0). Upon completion of bridging therapy, cytopenias requiring G-CSF administration prior to initiation of fludarabine/cyclophosphamide conditioning occurred in 18 pts with no difference between ST and RT cohorts (p=0.252). The median WBC and absolute lymphocyte count after bridging therapy and just prior to conditioning was 5.3 K/uL (range 1.5 -20.6) and 0.59 K/uL (range 0.07 - 1.9) respectively and was not statistically different between the ST and RT cohorts (p=0.851 and p=0.317). Twenty pts (62.5%) required G-CSF ≥ 14 days post CAR-T cell therapy infusion and did not differ between the groups (p=1.00). Rates of grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS) were 25% in the RT cohort and 63% in the ST group (p=0.106). Rates of grade ≥ 3 cytokine release syndrome (CRS) were 12.5% in the RT cohort compared to 16.7% among ST treated bridging patients (p=1.00). Rates of ICU admission were not significantly different between the groups (p=0.423). At a median follow up of 6.1 months (95% CI 4.0 - 6.9), there have been 13 deaths; the median OS for the entire bridging cohort has not been reached. Five deaths occurred due to toxicity (5/24 in the ST cohort and 0/8 in the RT group, p=0.296) as a result of infectious complications (n=3), ICANS (n=1) and hemophagocytic lymphohistiocytosis (HLH, n=1). Eight deaths occurred due to lymphoma (6/24 in the ST cohort and 2/8 in the RT cohort, p=1.00). For the entire bridging group of 32 pts, 13 experienced lymphoma progression with a median DSS of 4.4 months. The median DSS was 4.43 months among the ST cohort and not reached in the RT cohort (p=0.644). The PFS was 3.5 months for all bridging pts with a median PFS of 3.5 months among the ST treated pts and not reached for the RT pts (p=0.314). Conclusion: Bridging therapy is often utilized at physician discretion to temporize aggressive disease and facilitate successful CAR T-cell infusion. In this single institutional study, judicious use of bridging therapy permitted 91% of patients to undergo CAR-T cell infusion. This preliminary data suggests that RT can be an effective bridging tool for pts with R/R large B cell lymphoma prior to axi-cel therapy. Larger cohorts are required to determine if RT bridging strategies may result in lower rates of treatment related mortality and improved disease control. Figure Disclosures Pinnix: MD Anderson Cancer Center: Employment; Merck and Company: Research Funding; International Journal of Radiation Oncology Biology and Physics: Honoraria; Global Oncology One: Consultancy. Hawkins:Novartis Pharmaceuticals: Other: advisory panels. Westin:Curis: Other: Advisory Board, Research Funding; Novartis: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Janssen: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; MorphoSys: Other: Advisory Board; Unum: Research Funding; 47 Inc: Research Funding; Genentech: Other: Advisory Board, Research Funding. Fowler:Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Iyer:Novartis: Research Funding; Seattle Genetics, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; Incyte: Research Funding; Genentech/Roche: Research Funding; Arog: Research Funding. Parmar:Cellenkos Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang:Kite Pharma: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Research Funding; MoreHealth: Consultancy, Equity Ownership; BioInvent: Consultancy, Research Funding; VelosBio: Research Funding; Pulse Biosciences: Consultancy; Juno Therapeutics: Research Funding; Dava Oncology: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Aviara: Research Funding; BeiGene: Research Funding; Loxo Oncology: Research Funding. Neelapu:Poseida: Research Funding; Cell Medica: Consultancy; Precision Biosciences: Consultancy; Celgene: Consultancy, Research Funding; Merck: Consultancy, Research Funding; BMS: Research Funding; Acerta: Research Funding; Incyte: Consultancy; Novartis: Consultancy; Karus: Research Funding; Cellectis: Research Funding; Pfizer: Consultancy; Unum Therapeutics: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Allogene: Consultancy. Nastoupil:Bayer: Honoraria; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Spectrum: Honoraria.

Introduction. Cytokine release syndrome (CRS) and neurotoxicity (NT)(also known as immune effector cell-associated neurotoxicity syndrome or ICANS) are commonly observed after chimeric antigen receptor (CAR) T-cell therapy. While the clinical features of CRS have been extensively described, limited data exists for NT. Here, we report clinical and radiological features of NT after standard of care (SOC) axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Methods. Pts with r/r LBCL treated with SOC axi-cel at MD Anderson Cancer Center between 01/2018 and 04/2019 were included in the study. All pts received anti-seizure prophylaxis with levetiracetam starting on the day of axi-cel infusion for 30 days. CRS and NT were prospectively graded according to CARTOX criteria (Neelapu et al, Nat Rev Clin Oncol, 2018). Association between continuous variables were assessed using the bivariate Pearson correlation. Results. Ninety-five pts were included in the study, 72 (76%) with diffuse LBCL, 17 (18%) with transformed follicular lymphoma, and 6 (6%) with primary mediastinal LBCL. Median age was 60 (range, 18-85), 71 (75%) were male. Median number of previous therapies was 4 (range, 2-15), 26 (27%) had a previous autologous stem cell transplant (SCT), and 1 (1%) a previous allogeneic SCT. Eight (8%) pts had prior central nervous system lymphomatous involvement (parenchymal in 5), and 39 (41%) had prior neurological and/or psychiatric medical history. After axi-cel infusion, NT of any grade was observed in 65 (68%) pts, grade ³3 in 46 (48%)(Table). No significant association was observed between above outlined baseline characteristics and development of NT. Median time from axi-cel infusion to NT onset was 5 days (range, 0-25 days) and median duration was 6 days (range, 1-52 days); no new onset/recurrent NT was observed beyond day 30. Among the 65 pts who developed NT, a CT head without contrast was performed in 48, and was not evaluable in 2 because of motion artifacts. Among the 46 evaluable scans, 1 (4%) was abnormal as compared to baseline, and showed new onset cortical edema (non-diffuse but symmetrical). An MRI brain with contrast was performed in 36 pts, but was not evaluable in 10 because of lack of baseline, motion artifacts or differences in imaging sequences. Among the 26 evaluable scans, 15 (58%) showed abnormal findings, including autoimmune encephalitis-like, characterized by symmetric white matter changes of the pons and hippocampus (6; Fig. A), stroke-like (4; Fig. B), LMD-like (3; Fig. C) and PRES-like (2; Fig. D), with concomitant cortical edema in 5. EEGs were performed in 52 pts (>1/pt, for a total of 116 EEGs) and were abnormal in 47 (90%). Focal and/or diffuse slowing was the most common abnormality (isolated finding in 35 [73%] pts), while epileptiform discharges and/or non-convulsive status epilepticus (NCSE) were observed 12 (27%) pts. A lumbar puncture was performed in 12 pts: median white blood cell count was 2 cells/µL (range, 0-6), median protein 47 mg/dL (range, 13-600), median glucose 69 mg/dL (range, 30-111), and cytology was positive for malignant cells in 2 (7%) pts. Convulsive seizure was observed in 4 (6%) pts and 10 (15%) received additional anti-seizure therapy for convulsive or non-convulsive seizures. Among the 65 pts with NT, dexamethasone up to 20 mg IV Q6H was given to 42 (65%) pts, methylprednisolone 1000 mg IV daily to 12 (18%), and tocilizumab to 64 (98%; during CRS or CRS with concurrent NT). Overall, 93 (98%) pts developed CRS, grade >3 in 27 (28%). A significantly higher rate of NT of any grade (96% vs 57%, p3 (81% vs 35%, p3 CRS. After a median follow-up of 4 months, 6-month progression-free (PFS) and overall survival (OS) rates were 60% and 65%, respectively. Significantly shorter 6-month PFS (46% vs 80%, p=0.02) and OS rates (56% vs 83%, p=0.01) were observed among pts developing NT of any grade. Conclusions. Our results suggest that multiple radiological patterns of NT after axi-cel are possible in r/r LBCL pts, MRI being more sensitive than CT scan for their detection. NCSE is a common event, supporting the use of seizure prophylaxis and EEGs for evaluation of these pts. Pts with NT experience a worse outcome, and additional clinical and biological predictors of NT will be analyzed and presented at the meeting. Figure Disclosures Nastoupil: Spectrum: Honoraria; Janssen: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria. Westin:47 Inc: Research Funding; Novartis: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; MorphoSys: Other: Advisory Board; Unum: Research Funding; Curis: Other: Advisory Board, Research Funding; Genentech: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding; Janssen: Other: Advisory Board, Research Funding. Fowler:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lee:Seattle Genetics, Inc.: Research Funding. Parmar:Cellenkos Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang:Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; MoreHealth: Consultancy, Equity Ownership; Acerta Pharma: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; VelosBio: Research Funding; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Dava Oncology: Honoraria. Pinnix:Merck: Research Funding. Hawkins:Novartis Pharmaceuticals: Other: advisory panels. Neelapu:Precision Biosciences: Consultancy; Novartis: Consultancy; Allogene: Consultancy; Incyte: Consultancy; BMS: Research Funding; Cellectis: Research Funding; Poseida: Research Funding; Karus: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Cell Medica: Consultancy; Unum Therapeutics: Consultancy, Research Funding; Pfizer: Consultancy. Chi:Kite, A Gilead Company: Consultancy, Honoraria, Other: Kite Patient Management Advisory Board.

Introduction CAR-T cells targeting CD19 positive B-cells have improved outcomes and remission rates in relapsed/refractory non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). Although toxicities contributing to non-progression related mortality (NRM) have been reported in the pivotal trials, its incidence in the standard of care setting post-approval is unknown. The following data includes toxicity profiles implicated in events leading to NRM obtained from the FDA adverse event reporting system (FAERS) with comparison to MD Anderson (MDACC-L) CAR-T Lymphoma cohort and to the pivotal CAR-T trials. Methods We retrospectively queried FAERS for all adverse events (AE) associated with tisagenlecleucel (T) and axicabtagene ciloleucel (AC) reported from January 1, 2013-June 30, 2019. FAERS contains AEs from clinical trials and healthcare providers and is standardized according to the Medical Dictionary for Regulatory Activities (MedDRA), a clinically validated AE classification dictionary for pharmacovigilance monitoring. All cases with the outcome of death as reported by FAERS were queried. Cases in which the time to event with NRM was greater than 30 days or unknown were excluded. Total events recorded with NRM and disease progression were categorized according to the MedDRA coding system and compared using the chi-squared and a two-sided Fisher's exact test (statistical significance: p Results On FAERS, there were a total of 1184 reported cases, 669 with AC and 515 with T. Five cases were excluded because the reported event occurred 30 days after initiation of T (4) or AC (1), and 96 deaths were excluded because of missing start or event dates. As a result, there were 1,083 cases, 633 with AC and 450 with T. There were 101 (9.3%) deaths; 59 (13.1%) with T and 42 (6.6%) with AC. Seventy-six (7.0%) deaths were attributed to NRM; 39 (8.7%) with T and 37 (5.8%) with AC (Table 1) (Figure 1). AC had a significantly greater proportion of cytokine release syndrome (CRS) (p=0.027) and neurologic events (0.038) compared to T. The median number of days to the reported event was 4 (R: 0-27) for AC and 6 (R: 0-28) for T. There was no significant difference amongst cardiac, vascular, respiratory, or infectious events. There were 112 patients in the MDACC-L (108 received A and 4 received T), with 3 cases excluded due to non-availability of cause of death. There were 7 deaths for competing risk analysis between progression and NRM. At 30 days, the competing risk analysis for MDACC-L using the CIF for NRM was 2.74% (0.8-8.9%) when progression was used as a competing event. In comparison, the proportion of 30 day NRM with ZUMA-1 was 3%, JULIET was 0%, while ELIANA was 1.3%. Conclusions NRM, an important outcome measure in stem cell transplantation, needs to be clearly defined in CAR-T therapies. We present NRM events based on the largest dataset available, FAERS. This analysis highlights the major toxicities associated with NRM, time to event occurrence, and indicates potential opportunities for mortality reducing interventions. Competing risk analysis suggests NRM is 2.74% following axicabtagene ciloleucel treatment for lymphoma. The comparative data highlights the differences in the reporting, and the need for close monitoring of CAR-T specific AEs. It also reflects the limitation of FAERS such as missing data that may change the actual NRM, inability to differentiate the grade of a reported AE, and inability to determine the exact date of death. We plan to present this data with a profile of NRM events at the upcoming ASH meeting in Orlando. Disclosures Westin: Novartis: Other: Advisory Board, Research Funding; Kite: Other: Advisory Board, Research Funding; 47 Inc: Research Funding; Unum: Research Funding; MorphoSys: Other: Advisory Board; Genentech: Other: Advisory Board, Research Funding; Curis: Other: Advisory Board, Research Funding; Juno: Other: Advisory Board; Janssen: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding. Nastoupil:Spectrum: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Bayer: Honoraria. Nieto:Novartis: Research Funding; Affimed: Consultancy; Astra-Zeneca: Research Funding; Affimed: Research Funding. Parmar:Cellenkos Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding. Wang:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; MoreHealth: Consultancy, Equity Ownership; BioInvent: Consultancy, Research Funding; Loxo Oncology: Research Funding; BeiGene: Research Funding; Aviara: Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Dava Oncology: Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Research Funding; VelosBio: Research Funding; Juno Therapeutics: Research Funding. Hawkins:Novartis Pharmaceuticals: Other: advisory panels. Fowler:TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Neelapu:Celgene: Consultancy, Research Funding; Acerta: Research Funding; Novartis: Consultancy; Pfizer: Consultancy; Precision Biosciences: Consultancy; Allogene: Consultancy; Incyte: Consultancy; BMS: Research Funding; Cellectis: Research Funding; Karus: Research Funding; Unum Therapeutics: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Cell Medica: Consultancy; Poseida: Research Funding. Iyer:Arog: Research Funding; Bristol-Myers Squibb: Research Funding; Genentech/Roche: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Seattle Genetics, Inc.: Research Funding.

2540 Background: CAR-T cells targeting CD19 positive B-cells have improved outcomes for relapsed/refractory non-Hodgkin lymphoma (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). CAR-T emergent toxicities for FDA approved therapies leading to non-progression related death have been reported in the pivotal studies. However, they are underreported and there remains a need to obtain a comprehensive report of NRM emergent with anti-CD19 CAR-T. Methods: We retrospectively searched FDA adverse events reporting system (FAERS) for all adverse events (AE) related to “Tisagenlecleucel(T)” and “Axicabtagene ciloleucel(AC)” reported from 2013-2018. FAERS contains AEs from clinical trials and standard of care patients. All cases with the outcome of death were analyzed. Results: Total numbers of anti-CD19 CAR-T pts reported were 636, out of which 288 cases received “T” and 348 received “AC”. Out of total 129 total deaths, 95 died due to non-disease progression. Patient characteristics are summarized in Table. CART-NRM for entire cohort was 15%; 21% for “T” and 10% for “AC”. Major toxicities reported include CRS, hematological, cardiovascular, neurological and infectious. Difference in mortality is likely related to different patient population, diagnoses and the CAR-T construct. Conclusions: CART-NRM remains considerably high at 15%. Our analysis highlights the major toxicities and informs the potential opportunities for interventions to reduce mortality. We will present updated data with comparative analysis of published clinical studies at the upcoming ASCO Meeting in Chicago. [Table: see text]

Background Axicabtagene ciloleucel (axi-cel) is an autologous CD19-specific CAR T-cell therapy product that was FDA approved for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy. In the pivotal ZUMA-1 study, the best overall response (ORR) and complete response (CR) rates observed in 108 patients treated with axi-cel were 82% and 58%, respectively. At a median follow-up of 15.4 months, 42% of the patients remain in ongoing response (Neelapu et al. N Eng J Med 2017). Analysis of efficacy outcomes in patients Methods We retrospectively analyzed and reviewed the data from patients treated with axi-cel at our institution. Patients had a diagnosis of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), high-grade B-cell lymphoma (HGBCL), and transformed follicular lymphoma (TFL). Patients were treated with conditioning chemotherapy with cyclophosphamide and fludarabine for 3 days followed by axi-cel infusion after 2 days of rest at a dose of 2 x 106 CAR+ T cells/kg body weight. Patients were monitored for toxicities for at least 7 days in the hospital after CAR T infusion and those who had at least 30 days of follow-up after axi-cel were considered to be evaluable for safety. Cytokine release syndrome (CRS) and neurological toxicity termed as CAR-related encephalopathy syndrome (CRES) were graded according to the CARTOX grading system (Neelapu et al. Nat Rev Clin Oncol 2018). Results A total of 61 patients with relapsed or refractory large B-cell lymphoma who received axi-cel at our institution were included. Of these, 44 (72%) patients were CRS was common in both groups and was observed in 83% and 91% of the patients in the older and younger age groups, respectively. But most CRS events were grade 1-2. Grade 3 or higher CRS was observed in 18% vs. 11% in the older vs. younger age groups (P=0.67). One patient with a history of autoimmune disease in the elderly group died of hemophagocytic lymphohistiocytosis (HLH). CRES was observed in 58% and 71% of the patients in the older and younger age groups, respectively. Grade 3 or higher CRES was observed in 29% vs. 39% in the older vs. younger age groups (P=0.58). Median hospitalization period for axi-cel CAR T-cell therapy was comparable between the two groups. Conclusions Our results suggest that response rates are comparable between the elderly and younger age groups at day 30 after axi-cel therapy. Importantly, toxicities due to CRS and/or CRES after axi-cel CD19 CAR T cell therapy are comparable between the elderly (³65 years) and younger ( Table 1 Table 1. Disclosures Nastoupil: Merck: Honoraria, Research Funding; Janssen: Research Funding; Juno: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; TG Therappeutics: Research Funding; Karus: Research Funding; Celgene: Honoraria, Research Funding; Spectrum: Honoraria; Gilead: Honoraria. Fowler:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Samaniego:ADC Therapeutics: Research Funding. Wang:Kite Pharma: Research Funding; Acerta Pharma: Honoraria, Research Funding; Novartis: Research Funding; Juno: Research Funding; Pharmacyclics: Honoraria, Research Funding; Dava Oncology: Honoraria; AstraZeneca: Consultancy, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; MoreHealth: Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Westin:Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Apotex: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Celgen: Membership on an entity's Board of Directors or advisory committees.