ALBERT

Description: The "7+3" regimen is recommended for treatment in patients with new diagnosis of acute myeloid leukemia (AML) who are fit for intensive chemotherapy. Patients with secondary AML (sAML) [i.e. AML evolving from antecedent hematologic disorders (AHD-AML) or after previous exposure to chemo/radiation therapy for unrelated cancer (t-AML)], have inferior outcomes with "7+3" regimen. A recent phase 3 study demonstrated superior CR rates and overall survival (OS) with upfront use of CPX-351 compared to "7+3" regimen in older patients (≥60 years) with sAML (Lancet et al JCO 2018). The combination of HMA+Ven is FDA approved for upfront treatment in newly diagnosed AML patients 〉 75 or those unfit for intensive chemotherapy based on CR+ CRi rates of 67% and median OS of 17.5 months. Herein, we compared the outcomes of older patients with sAML who received upfront treatment with either HMA+Ven or CPX-351 at our institution. Our analysis includes 47 consecutive patients with previously untreated sAML treated between 2018-2020 . Patients were treated with either HMA+Ven (n=27) or CPX-351 (n=20) based on physician preference. WHO criteria were used for the diagnosis AHD-AML and review of medical records for documenting exposure to leukemogenic agent for t-AML. Complete remission (CR) was defined by presence of 1000/µL and platelets ≥100,000/µL) were defined as CRh (hematologic recovery) and CR without blood count recovery as CRi (incomplete blood count recovery). Minimal residual disease (MRD) assessment was done on day-28 BM aspirate using multiparametric flow cytometric assay with lower limit of sensitivity of 0.01%. Patients demographic and disease features are summarized in Table 1. Mean age (p=0.39), mean blast percentage in BM aspirate (P=0.82), high-risk cytogenetics (P=0.37) and high-risk molecular mutations (P=0.737) were similar in both treatment groups. Of the 27 cases of sAML in HMA+Ven group, 8 were t-AML arising after prior chemotherapy (Hodgkin's Disease n=2; paraganglioma, desmoid tumor, breast cancer, NHL, multiple myeloma, ALL: one each) while 19 were AHD-AML. In CPX-351 group, 6 cases were t-AML arising after prior chemotherapy (NHL n=2, breast cancer n=2, T-Lymphoblastic Lymphoma and colon cancer one each) while 14 were secondary to AHD. The mean number of cycles were 3.3 (range 1-18) in HMA+Ven group and 1.45 (1-3) in CPX-351 group. Two-sample t test was used to compare continuous and normally distributed covariates, such as age and BM blasts, between HMA+Ven or CPX-351 arms. Pearson Chi-square or Fisher exact test was used to assess the associations between treatment and clinical outcomes. Kaplan-Meier method and log-rank test were used to assess OS or LFS. A P value of ≤ 0.05 was considered as statistically significant. The CR rate in patients treated on HMA+Ven group was 78% (n=21; 95% CI: 58-91%) vs 50% (n=10; 95% CI: 27-73%) in CPX-351 group (P=0.047). CRi was achieved in 52% (n=14) patients in HMA+Ven group compared to 25%(n=5) patients in CPX-351 group(p=0.064). MRD negative remission was achieved in 52% (n=14) patients in HMA+Ven group and in 25% (n=5) patients in CPX-351 group (p=0.064). In HMA+Ven group, 52% patients (n=14) achieved remission after one cycle of therapy compared to 45% (n=9) patients in CPX-351 arm (p=0.642). With a median follow-up of 6.7 months for all patients, the median leukemia free-survival (LFS) for HMA+Ven vs CPX-351 treatments is 16.2 vs NA months (P = 0.098) and the median OS is 13.2 vs NA months (P = 0.395). Ten patients in each group (37% in HMA+Ven and 50% in CPX-351; p=0.47) underwent allo-HCT. At last follow up, 14 patients (52%) have died in HMA+Ven group from: relapsed AML (n=10), sepsis (n=2), congestive heart failure (n=1) and unknown (UK) in one patient, whereas in CPX-351 group, 8 patients (40%) have died from relapsed AML in (n=5), respiratory failure (n=2) and UK causes in one patient. In patients resistant to initial therapy, the median OS is 3.5 vs 6.0 months between HMA+ Ven and CPX-351 groups (P = 0.224). Conclusion: In patients presenting with sAML, upfront treatment with HMA+Ven is feasible and associated with significantly better CR rates and a favorable trend for higher rates of negative MRD compared to CPX-351. A randomized prospective trial in patients with sAML is warranted to determine the most effective frontline regimen in this high-risk AML subgroup. Disclosures Salhotra: Celgene: Research Funding; Kadmon: Membership on an entity's Board of Directors or advisory committees. Al Malki:Rigel Pharma: Consultancy; Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy. Aribi:Seattle Genetics: Consultancy. Ali:Incyte Corporation: Consultancy. Budde:Gilead Sciences: Consultancy; Merck: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Consultancy; Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding; Roche: Consultancy. Dadwal:Ansun Biopharma: Research Funding; Karius: Research Funding; Shire/ Takeda: Research Funding; Gilead: Research Funding; Merck: Consultancy, Honoraria, Other: Advisory board meeting, Research Funding, Speakers Bureau; Chimerix: Research Funding; Janssen: Other: Advisory board meeting; Astellas: Speakers Bureau. Nakamura:NapaJen Pharma: Consultancy; Kadmon Corporation: Other: Advisory board meeting; Viracor: Consultancy; Magenta Therapeutics: Other: Advisory board meeting; Celgene: Other: Support on seminar; Kyowa-Kirin: Other: Support on a meeting presentation; Alexion: Other: Support on a meeting presentation; Merck: Other: advisory board meeting. Stein:Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau. Marcucci:Takeda: Other: Research Support (Investigation Initiated Clinical Trial); Merck: Other: Research Support (Investigation Initiated Clinical Trial); Iaso Bio: Membership on an entity's Board of Directors or advisory committees; Abbvie: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Other: Research Support (Investigation Initiated Clinical Trial). Pullarkat:Dova: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genetech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie, Inc.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: off label use of HMA+venetoclax in secondary AML

Description: Background: Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is approved for treatment of adult pts with R/R LBCL after ≥ 2 lines of systemic therapy. In the pivotal ZUMA-1 study, axi-cel demonstrated durable responses and a largely manageable safety profile (Locke FL, et al. Lancet Oncol. 2019). ZUMA-9 (NCT03153462), a multicenter, open-label study, provided pts with R/R LBCL with expanded access to axi-cel until commercial availability (Cohort 1 [C1]) and later, if commercially manufactured product did not meet commercial release specification(s) (Cohort 2 [C2]). Safety and efficacy of axi-cel (C1 and C2) and translational analyses (C2) are presented. Methods: Eligible adults had histologically confirmed R/R LBCL, ECOG ≤ 1, and received prior CD20-targeting and an anthracycline-containing regimen. C2 pts must have had commercial OOS product. Pts underwent leukaphersis and conditioning chemotherapy (cyclophosphamide 500 mg/m2/day and fludarabine 30 mg/m2/day) for 3 days followed by a single axi-cel infusion (target dose, 2 × 106 CAR T cells/kg). C1 and C2 pts with high disease burden could receive bridging therapy before conditioning at investigator's discretion. Endpoints included frequency of adverse events (AEs), objective response rate (ORR) per standard-of-care imaging assessment, overall survival (OS) for C1 and C2, and blood CAR T cells levels and serum cytokines for C2 only. Outcomes were contextualized with the primary analysis of ZUMA-1 C1+2 (n = 101; ≥ 6 mo of follow-up; Neelapu SS, et al. NEJM. 2017). Results: As of 11/29/2019 (C1) and 3/15/2020 (C2), 25 C1 pts and 36 C2 pts received axi-cel with a median follow-up of 27.1 mo (range, 23.6 - 29.6) and 13.2 mo (range, 0.4 - 25.7), respectively. In C1, median age was 56 y (range, 28 - 76), 60% were male, 80% had DLBCL, 48%/0% had ECOG1/≥2, 44% had IPI ≥3, and 64% had ≥ 3 prior lines of therapy. In C2, median age was 61 y (range, 24 - 81), 75% were male, 78% had DLBCL, 58%/17% had ECOG 1/≥2, 56% had IPI ≥3, and 69% had ≥ 3 prior lines of therapy. In C2, 50% of pts had OOS product with low viability, 28% had high IFN-γ, 14% had low IFN-γ, 14% received a low dose, and 6% had high transduction ratio. The ORR was 76% (64% complete response [CR]) for C1, 53% (36% CR) for C2, and 82% (54% CR) for ZUMA-1 C1+2. Median OS was 23.8 mo (95% CI, 13.5 - NE) for C1 and not reached (95% CI, 3.4 - NE) for C2, respectively. ORR and OS were consistent in C2 OOS subgroups (Table). Grade ≥ 3 AEs were reported in 88% and 89% of C1 and C2 pts, respectively. Grade ≥ 3 CRS (Lee et al, Blood. 2014) was not observed in C1 but was reported in 3% of C2 pts (13% in ZUMA-1 C1+2). Grade ≥ 3 neurologic events (NEs) occurred in 36% and 19% of pts in C1 and C2, respectively, and 28% of pts in ZUMA-1 C1+2. No Grade 5 CRS or NEs occurred in C1 or C2. All CRS and NEs resolved in C1, and most CRS (29/30) and NEs (19/24) resolved in C2 as of the data cutoff. Of 3 Grade 5 AEs in C1, 2 were unrelated to axi-cel (clostridial sepsis [on Day (D) 6] and respiratory failure [on D212]) and 1 was related to conditioning (myelodysplastic syndrome [on D563]). Of 3 Grade 5 AEs in C2, 2 were unrelated to axi-cel (multiple organ dysfunction syndrome [on D6] and cardiac arrest [on D482]) and 1 was related to axi-cel (systemic mycosis [on D30]). Median peak CAR T cell levels and median CAR T cell expansion (area under the curve in the first 28 days) were lower in ZUMA-9 C2 (n = 32/36; 12 cells/µL [range, 0 - 442] and 112 cells/µL × days [range, 0 - 3413]) vs ZUMA-1 C1+2 (n = 96/101; 42 cells/µL [range, 1 - 1514] and 462 cells/µL × days [range, 5 - 14,329]). Serum IFN-γ levels peaked within 8 days after axi-cel infusion (median, 170 pg/mL [range, 8 - 1876]) and were lower vs ZUMA-1 C1+2 (median, 477 pg/mL [range, 8 - 8209]). Axi-cel in ZUMA-9 C2 contained fewer, less differentiated CCR7+ naïve and central memory T cells, and a greater proportion of more differentiated CCR7- effector memory and effector T cells vs ZUMA-1 C1+2. No cases of replication-competent retroviruses were reported in C1 or C2. Conclusion: Axi-cel treatment demonstrated a manageable safety profile and meaningful clinical benefit in this expanded access and OOS product study. While CAR T cell therapy showed clinical benefit in C2 (OOS product), the lower CR rate was corroborated by lower CAR T cell expansion and a more differentiated product vs ZUMA-1 C1+2, warranting further investigation. ZUMA-9 C2 is enrolling pts and evaluation is ongoing. Disclosures Jacobson: Precision Biosciences: Consultancy, Honoraria, Other: travel support; Celgene/BMS: Consultancy, Honoraria, Other: travel support; Novartis: Consultancy, Honoraria, Other: travel support; AXIS: Speakers Bureau; Nkarta: Consultancy, Honoraria, Other: travel support; Clinical Care Options: Speakers Bureau; Pfizer: Research Funding; Lonza: Consultancy, Honoraria, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: travel support. Locke:Calibr: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Wugen: Consultancy; GammaDelta Therapeutics: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy; Novartis: Consultancy; Cellular Biomedicine Group: Other: Consultancy with grant options; Allogene: Consultancy. Miklos:Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding; Miltenyi Biotec: Research Funding; Janssen: Consultancy, Other: Travel support; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Vose:Incyte: Research Funding; Novartis: Research Funding; Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Allogene: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Miltenyi Biotec: Honoraria; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Kite, a Gilead Company: Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Verastem: Consultancy, Honoraria; Wugen: Honoraria; Celgene: Honoraria; Roche/Genetech: Consultancy, Honoraria, Other. Lin:Sorrento: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Vineti: Consultancy; Gamida Cells: Consultancy; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Legend BioTech: Consultancy; Juno: Consultancy; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding. Budde:Roche: Consultancy; Merck: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Consultancy; Gilead Sciences: Consultancy; Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding. Maloney:Celgene: Consultancy, Honoraria, Research Funding; A2 Biotherapeutics: Consultancy, Current equity holder in publicly-traded company, Honoraria; Gilead Sciences: Consultancy, Honoraria; Juno Therapeutics: Consultancy, Honoraria, Patents & Royalties: Patents are pending, but not issued, licensed, no royalties, no licensees., Research Funding; Bioline Rx: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Jaglowski:Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy; Novartis: Consultancy, Research Funding. Riedell:MorphoSys: Research Funding; Kite/Gilead: Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Karyopharm Therapeutics: Consultancy; Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding. Perales:Celgene: Honoraria; MolMed: Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Honoraria, Research Funding; Miltenyi Biotec: Research Funding; Merck: Consultancy, Honoraria; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Cidara Therapeutics: Other; Servier: Membership on an entity's Board of Directors or advisory committees, Other; Medigene: Membership on an entity's Board of Directors or advisory committees, Other; NexImmune: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Honoraria, Research Funding. Kim:Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Kawashima:Kite, a Gilead Company: Current Employment; Gilead Sciences: Other: stock or other ownership . Yang:Kite, a Gilead Company: Current Employment. Rossi:Kite, a Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Goyal:Kite, a Gilead Company: Current Employment. Neelapu:Legend Biotech: Other; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Unum Therapeutics: Other, Research Funding; Adicet Bio: Other; 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; Precision Biosciences: Other: personal fees, Research Funding; Poseida: Research Funding; Calibr: Other; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Karus Therapeutics: Research Funding; Cellectis: Research Funding; N/A: Other.

Description: Introduction Chimeric Antigen Receptor (CAR) T cell therapy has improved outcomes for relapsed and/or refractory (r/r) B cell lymphomas. Bridging therapy might be needed in some patients for disease control while CAR T product is being produced. Radiation therapy is known to control the growth of lymphoma and modulate tumor microenvironment, however use of this therapy in the setting of CAR T cell therapy has not been well described. In the present study, we report the efficacy and toxicities of patients treated with a dose of radiation that is lower than previously described for bridging in lymphoma and compare efficacy and toxicities to patients treated with chemotherapy bridging or without bridging therapy. Methods We retrospectively compared rates of toxicities and outcomes of 82 patients treated with FDA approved CD19-directed CAR T cells at our institution between November 1, 2018 and April 1, 2020. This study was conducted with approval from the City of Hope National Medical Center Institutional Review Board. All patients received standard lymphodepleting chemotherapy (LDP) regimen with cyclophosphamide and fludarabine followed by infusion of CAR T cells at day 0. Clinical response was determined 28-35 days following cell administration. Median dose of radiation treatment was 24 Gy (range 4 - 44) in 1.8 - 2.25 Gy fractions. Chemotherapy regimens were at provider discretion. Results From our institutional database of 82 patients, a total of 7 patients received radiation as bridging therapy. All received the predefined radiation doses with no significant immediate complications. Target organs included the head and neck (4), limbs (2), and chest wall. Structures threatened by the progressing disease included neurovascular (4), limb threatening (2), and major organ threatening (5). All threatened sites were preserved with the use of radiation therapy. 72% of patients receiving RAD had disease that was primary refractory to chemotherapy. The characteristics of patients treated with radiation bridging (RAD) were similar to those treated with chemotherapy bridging (CB) or without bridging (NB), except that patients treated with RAD tended to have less extensive disease (table 1). The adverse rates of CAR T treatment emergent toxicity (CRS, neurotoxicity, hematologic toxicity, or infectious rates) in the RAD group were 83%, 50%, 83%, and 33% respectively. These are comparable to the CB or NB groups (table 2). Response rates were similar among the three groups with ORR 86% for RAD, 88% for CB, and 93% for the NB group (p = 0.98). Rates of progressive disease were the lowest in the RAD group (14%), followed by NB (21%) and CB (42%) after a median follow up of 241 days (range 43 - 785), however this did not reach statistical significance (p = 0.44). Discussion In the present study we demonstrate real world rates of toxicities in patients receiving bridging chemo or bridging radiation. The rates of toxicities were similar regardless of the type of bridging that was utilized. In addition, there was no statistically significant difference in response or relapse rates among the different groups. There was a trend toward lower relapse rates among those treated with radiation. Importantly, this trend was seen even though the majority of radiation doses given were lower than previously described for this indication. Importantly, the vital structures that were threatened by lymphoma were effectively preserved with the utilization of radiation therapy in this setting even with the majority of cases having primary chemo-refractory disease. Additional studies using higher patient number will be needed to strengthen this observation. Our study also sets the stage for future prospective studies optimizing the role of radiation in CAR T cell therapy. Disclosures Shouse: Kite Pharma: Honoraria, Speakers Bureau. Budde:Mustang Therapeutics: Research Funding; Merck: Research Funding; Amgen: Research Funding; Kite, a Gilead Company: Consultancy; Gilead Sciences: Consultancy; Roche: Consultancy; AstraZeneca: Research Funding.

Description: Introduction City of Hope (COH) was one of the first institutions to be granted Immune Effector Cell (IEC) Therapy accreditation by the Foundation for the Accreditation of Cellular Therapy, which supports our mission to provide safe, high quality patient care through expanded standardization. As part of the accreditation requirements, COH expanded established processes developed to monitor standard of care (SOC) deviations for the Hematopoietic Cell Transplantation Program to our IEC Clinical Program. As part of process improvement, we monitored our IEC Quality program to determine if there were any outcome changes as a result of deviations. Therefore, we performed a retrospective analysis of electronically submitted SOC deviations for patients treated with commercially available chimeric antigen receptor (CAR) T cell products (tisagenlecleucel or axicabtagene ciloleucel [Axi-cel]) between December 2017- March 2020 at COH. Methods During the reporting timeframe, 122 patients were planned to be treated with an IEC product. We retrieved 28 requests for SOC deviations from our electronic database for 24 of 122 patients. We analyzed for volume, trends and patient outcomes of submitted deviation requests, including trends in type of deviation, transfer to the intensive care unit (ICU), length of inpatient hospital stay and safety outcomes at 30 days post infusion. Patients who did not receive their SOC product for any reason during the reporting timeframe, or were lost to follow-up were excluded from the outcomes analysis. Results Sixteen of 24 patients were planned to be treated with SOC Axi-cel and 8 of 24 patients were planned to be treated with tisagenlecleucel; only 19 of 24 patients (10 women and 9 men) underwent infusion with their respective SOC product, 15 with Axi-cel and 4 with tisagenlecleucel. Five of 24 patients, including 1 Axi-cel and 4 tisagenlecleucel patients were excluded due to change in medical condition or infusion after the reporting timeframe. We identified elevated creatinine levels as the most common reason for SOC deviation requests for patients to be treated with tisagenlecleucel (4 of 8 patients), while deviations relating to rest days between lymphodepletion and CAR T cell infusion were the most common submitted deviations for patients planned to be treated with Axi-cel (9 of 16 patients). We also descriptively compared patients who required SOC deviations to a cohort of patients (n=98) who did not require deviations and were treated with either axicabtagene ciloleucel (n=86) or tisagenlecleucel (n=12) during the same timeframe. Eight of 98 (8%) of patients who did not have requests for SOC deviation were transferred to the ICU compared to 4 of 19 (21%) patients who required SOC deviations. Seventeen of 19 and 94 of 98 patients were discharged. The median length of inpatient hospital stay post infusion for SOC deviations cohorts who were discharged was 16 days (11-40) and 15 days (8-100) for non-SOC deviations patients. When we descriptively compared survival outcomes at 30 days post infusion, we found that all (4 of 4) patients who required SOC deviations and received tisagenlecleucel survived compared to 11 of 12 patients without SOC deviations. For patients who received Axi-cel, 14 of 15 patients with SOC deviations survived at day 30 post infusion compared to 85 of 86 patients without SOC deviations. The response to treatment and toxicities will be reported at the meeting. Conclusion These data suggest that careful selection of patients who may benefit from SOC deviations and still receive their infusion may not negatively affect survival outcomes at 30 days. The SOC deviation review process offers physicians a forum to evaluate non-SOC eligible cases and advise on SOC policy changes. While preliminary, our quality review identifies a role for comprehensive analysis of all IEC SOC deviations as part of standard practice, especially as the field of cellular immunotherapy expands to include more SOC cellular products. Overall, further monitoring of SOC deviations in real world patient populations treated with commercially available IEC products will allow us to continue to support patient safety, assess patient care management practices, expand patient access, meet accreditation standards and monitor SOC practice changes while advancing the field of cellular immunotherapy. Disclosures Shouse: Kite Pharma: Honoraria, Speakers Bureau. Mott:Janssen/Johnson & Johnson: Consultancy; Juno/BMS: Consultancy. Budde:Gilead Sciences: Consultancy; AstraZeneca: Research Funding; Merck: Research Funding; Mustang Therapeutics: Research Funding; Kite, a Gilead Company: Consultancy; Roche: Consultancy; Amgen: Research Funding.

Description: Introduction The most common toxicities after chimeric antigen receptor (CAR) T cell therapy include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and hematologic toxicity. The reported grade 3 and higher neutropenia, anemia and thrombocytopenia lasting longer than 30 days occurred in 15%, 3% and 18% of patients treated with Axicabtagene ciloleucel (Axi-Cel) (Yescarta package insert). Early hematologic toxicity after lymphodepleting chemotherapy (LDP) prior to infusion of CAR T cells is expected. However, prolonged cytopenias lasting longer than 28 days cannot be explained by the toxicity of LDP alone. Here, we described the incidence and potential causes for prolonged cytopenias in patients (pts) treated with Axi-cel for r/r aggressive B cell lymphoma. Methods We retrospectively analyzed 78 consecutive pts receiving Axi-cel at our institution between November 1, 2017 and April 1, 2020. This study was conducted with approval from the COH Institutional Review Board. All patients received standard LDP regimen with cyclophosphamide and fludarabine followed by infusion of Axi-cel at day 0. Clinical response was determined between day 28-35. Neutropenia, anemia and thrombocytopenia were defined as meeting the NCI CTCAE v5.0 criteria and were considered prolonged if lasting 〉28 days. CRS and ICANS severity were graded using the ASTCT criteria. Results A total of 78 pts were included with the median age of 61 years (range, 22-77), 33% 〉 65 years old, 68% male. Seventeen (22%) pts had transformed follicular lymphoma (tFL), 55 had diffuse large (DLBCL), and 6 (8%) had primary mediastinal (PMBCL). Median lines of prior treatment were 3 (range 2-6) with 18 (23%) having prior autologous stem cell transplant (ASCT). Responses were seen in 71 pts (91%), with 25 (32%) partial responses (PR) and 46 (59%) complete responses (CR) at the first assessment. Forty-eight pts (62%) remained progression free with a median follow up of 252 days (range, 56-785). CRS was noted in 67 pts (86%), with 6 (8%) grade 3 (G3), while 35 (45%) developed ICANS, with 8 (10%) G3. No grade 4 or higher CRS or ICANS were seen. All pts developed ≥ G3 neutropenia and lymphopenia that lasted a median of 51 days (range 7-456), and 39 days (range 6-737) respectively. G3 and higher anemia and/or thrombocytopenia were seen in 49% of pts. Prolonged ≥ G3 cytopenias were seen in 72% of pts with 47%, 23%, and 29% showing prolonged neutropenia, anemia and thrombocytopenia respectively. Importantly, CRS was associated with a statistically significant increase (79% vs 27%) in risk of developing prolonged cytopenias (p=0.001). In addition, a biphasic pattern of hematologic toxicity in which late cytopenias recurred after a period of recovery, was noted in 8% of pts. These delayed cytopenias were associated with lymphocyte recovery after CAR T cell administration. Finally, 7% of pts with prolonged ≥ G3 cytopenias developed therapy related MDS: the median age in this group was 60 (range 50-74), with a median of 3 prior lines of therapy (range 2-4), and 75% having prior ASCT. Overall, infections were seen in 14 pts (18%) and 9 were after day 28. In pts with prolonged ≥ G3 neutropenia, rates of infection beyond day 28 (9%) were similar to those without prolonged neutropenia (8%). Use of GCSF did not correlate with increased CRS, ICANS or prolonged cytopenias. Conclusion Our real-world experience reported high response rates and favorable incidences of CRS, and ICANS with no grade 4 noted in comparison to that described in clinical trials and by others. We identified CRS as a significant risk factor associated with development of prolonged hematologic toxicity and this may indicate an underlying bone marrow suppressive effect of the inflammation associated with CRS. Like others, we also observed a biphasic hematologic toxicity associated with recovery from B cell aplasia. Due to significant rates of therapy related MDS, bone marrow evaluation before and after CAR T therapy should be considered, especially in patients with prior transplant. Last, despite the high rates of prolonged hematologic toxicity, infection rates were not higher in patients with prolonged neutropenia, underscoring the importance of supportive medical management. Disclosures Shouse: Kite Pharma: Honoraria, Speakers Bureau. Mei:Sanofi: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees. Herrera:AstraZeneca: Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Seattle Genetics: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Karyopharm: Consultancy. Zain:Seattle Genetics: Research Funding; Mundi Pharma: Research Funding; Kyowa Kirin: Research Funding. Siddiqi:BeiGene: Consultancy, Research Funding; Juno: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Speakers Bureau; TG Therapeutics: Research Funding; Celgene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Seattle Genetics: Speakers Bureau; Oncternal: Research Funding; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Popplewell:Pfizer: Research Funding; Novartis: Research Funding; Roche: Research Funding. Budde:Amgen: Research Funding; Merck: Research Funding; Mustang Therapeutics: Research Funding; AstraZeneca: Research Funding; Roche: Consultancy; Gilead Sciences: Consultancy; Kite, a Gilead Company: Consultancy.

Description: Introduction: HDT-AHCT is a standard and potentially curative therapy for patients with high risk, chemosensitive lymphomas. Improvements in supportive care and HCT practices have led to increasing use of HDT-AHCT worldwide particularly in elderly and more comorbid patients at higher risk of complications. However, HDT is associated with severe regimen-related toxicities (SRRT) which lead to considerable symptom burden and in some cases, life-threatening organ toxicities. Moreover, the risk of SRRT is a significant concern and may lead to patients being denied a potentially curative therapy. Although SRRT can affect many organs, the most commonly affected are those with high cell turnover, including the hematopoietic system and oral-gastrointestinal tract (oral/GI tract). While the hematopoietic system is rescued by AHCT, there are no effective therapies to substantially reduce SRRT. AB-205 is a novel experimental engineered-cell therapy intended to reduce SRRT associated with HDT-AHCT. AB-205 contains clinical-grade, allogeneic E4ORF1+ CD31+ umbilical vein endothelial cells, or 'universal' E-CEL® cells, and has been shown to accelerate the recovery of the vascular niches in various organs through autocrine and juxtacrine mechanisms of action on resident tissue capillary endothelial cells and resident progenitors in preclinical studies. It also has a beneficial effect in chaperoning exogenously administered stem cells. Here we report results of a Phase I study of AB-205 in adults with lymphoma undergoing HDT-AHCT. Methods: The primary objective is to assess the safety of AB-205. Secondary objectives include assessment of grade (G) ≥ 3 AEs (NCI-CTCAE v5.0), G ≥ 3 oral/GI SSRT (defined as oral mucositis (OM), nausea, vomiting and diarrhea) and time to neutrophil and platelet engraftment. Subjects with chemosensitive lymphomas who are eligible for HDT-AHCT using myeloablative conditioning regimens were enrolled. Three dose-levels have been tested: 5, 10 and 20 x 106 cells/kg. AB-205 is administered intravenously after and on the same day (D) as AHCT. The highest level (20x106 cells/kg) was given either as single dose on D0 or split into equal doses on D0 and D2. Results: As of 9th July, 2020, 31 subjects had been treated with AB-205. Median follow-up was 132 D (range, 3-352). 24 subjects had systemic lymphoma (6 HL, 18 NHL) and were treated with BEAM, BeEAM or CBV. 7 subjects had lymphoma with CNS involvement (5 primary CNS lymphoma) and were treated with TBC. Median (range) lines of prior therapy was 2 (1-4) and 1 (1-4) for the groups respectively. Median infused CD34+ dose was 4.74 x 106 cells/kg (range: 2.00, 8.38). No maximum tolerated dose has been established through dosing up to 20 x 106 cells/kg. One DLT, prolonged thrombocytopenia (D32), occurred with 10 x 106 cells/kg. Treatment emergent AEs were consistent with those expected in subjects undergoing HDT-AHCT. At the time of last follow-up, one subject with primary CNS lymphoma died after cognitive decline (D166) and one subject had disease relapse (D101). AB-205 therapy was associated with low rates of G ≥3 oral/GI SRRT (Table 1). Effects were most pronounced among subjects with systemic lymphoma who had no (0%) G ≥3 nausea, vomiting, or diarrhea at any dose level, and only one subject (4%) with G3 OM (at the 10 x 106 cells/kg dose level). No G ≥3 oral/GI SRRTs have been reported in systemic lymphoma in 13 subjects who received 20 x 106 cells/kg (single or split dose). No other G ≥3 SRRT such as nephritis, pneumonitis or carditis was observed. In addition to dose dependent reduction of oral/GI SRRT, a trend for a dose dependent decrease in the incidence of febrile neutropenia (FN) was observed (Table 1). Median (IQR) time to neutrophil and platelet engraftment was 10 D (9-11) and 11 D (9-13) respectively. In 21 (68%) subjects, platelet engraftment occurred prior to or within 1 day of neurophil engraftment. Conclusion: AB-205 appears to be safe and potentially effective in subjects undergoing HDT-AHCT for lymphoma. Compared to published rates of 24-41% for G ≥3 OM (Singer 2019; Colita 2109) and 86% for FN (Caimi 2105) in subjects with systemic lymphoma, we observed 0% SRRT and 31% FN with the highest dose of AB-205 tested. AB-205 has significant potential to address a serious unmet medical need in patients undergoing HDT-AHCT and will be assessed in a forthcoming pivotal, double-blinded, placebo-controlled, randomized clinical trial for potential registration. Disclosures Scordo: McKinsey & Company: Consultancy; Omeros Corporation: Consultancy; Kite - A Gilead Company: Other: Ad-hoc advisory board; Angiocrine Bioscience, Inc.: Consultancy, Research Funding. Budde:Amgen: Research Funding; AstraZeneca: Research Funding; Mustang Therapeutics: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Consultancy; Gilead Sciences: Consultancy; Roche: Consultancy. Abedi:BMS, Gilead Sciences: Research Funding; AbbVie, BMS, Gilead Sciences, Seattle Genetics, Takeda: Speakers Bureau. Fakhri:University of California San Francisco: Current Employment. Dholaria:Takeda: Research Funding; Angiocrine: Research Funding; Poseida: Research Funding; bms: Research Funding; J&J: Research Funding. Kavalerchik:Angiocrine Bioscience: Current Employment, Current equity holder in private company; California Institute for Regenerative Medicine: Research Funding; Abbvie: Current equity holder in publicly-traded company. Aggarwal:Angiocrine Bioscience: Current Employment, Current equity holder in private company; Kadmon Corp: Current equity holder in publicly-traded company. Qazilbash:Janssen: Research Funding; Angiocrine: Research Funding; Bioclinica: Consultancy; Amgen: Research Funding; Bioline: Research Funding. Finnegan:Angiocrine Bioscience: Current Employment. Giralt:ACTINUUM: Consultancy, Research Funding; OMEROS: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria; CELGENE: Consultancy, Honoraria, Research Funding; TAKEDA: Research Funding; AMGEN: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; KITE: Consultancy.