Nastoupil, Loretta J.

AbstractThe multicenter, phase Ib CC‐122‐DLBCL‐001 dose‐expansion study (NCT02031419) explored the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC‐122) plus rituximab in patients with relapsed/refractory (R/R) diffuse large B‐cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received avadomide 3 mg/day 5 days on/2 days off plus rituximab 375 mg/m2 on day 8 of cycle 1, day 1 of cycles 2 through 6, and day 1 of every third subsequent cycle for 2 years. Primary endpoints were safety and tolerability; preliminary efficacy was a secondary endpoint. A total of 68 patients were enrolled (DLBCL [n = 27], FL [n = 41; 31 lenalidomide‐naïve, 10 lenalidomide‐treated]). Median age was 62 years (range, 33–84 years), and patients had received a median of 3 (range, 1–8) prior regimens. Among patients with DLBCL, 66.7% had primary refractory disease (partial response or less to initial therapy). Among patients with FL, 65.9% were rituximab‐refractory at study entry and 10.0% were lenalidomide‐refractory. The most common any‐grade avadomide‐related adverse events (AEs) were neutropenia (63.2%), infections/infestations (23.5%), fatigue (22.1%), and diarrhea (19.1%). The most common grade 3/4 avadomide‐related AEs were neutropenia (55.9%) infections/infestations (8.8%), and febrile neutropenia (7.4%). In patients with DLBCL, overall response rate (ORR) was 40.7% and median duration of response (mDOR) was 8.0 months. In patients with FL, ORR was 80.5% and mDOR was 27.6 months; response rates were similar in lenalidomide‐naïve and ‐treated patients. Avadomide plus rituximab was well tolerated, and preliminary antitumor activity was observed in patients with R/R DLBCL and FL, including subgroups with typically poor outcomes. These results support further investigation of novel CELMoD agents in combination with rituximab in R/R DLBCL and FL.

Abstract Background: Differences in outcomes between clinical trial and real-world populations in follicular lymphoma (FL) may be partially explained by differences in characteristics between clinical trial and real-world patients. We hypothesized that certain eligibility criteria may be responsible for populations with distinct demographic/clinical characteristics. In this study, we compiled a list of eligibility criteria from front-line FL trials and evaluated their impact on the potentially eligible FL patients derived from two national cohort studies. We also evaluated whether criteria were duplicative and whether liberalizing criteria might enlarge the pool of eligible patients. Methods: Eligibility criteria were abstracted from 21 first-line clinical trials in FL in the FLASH database. We identified FL patients in two prospective cohort studies: Molecular Epidemiology Resource (MER) and Lymphoma Epidemiology of Outcomes (LEO). Descriptive statistics were used to characterize patients included and excluded by various eligibility criteria. Chi-square tests and two-sample t-tests were used to compare categorical and continuous variables, respectively. To study the relative impact of individual criteria, we used a step-wise approach to quantify the number of additional patients excluded with each individual criterion after applying other criteria. Results: Eligibility criteria included in at least one-third of studies included stage (present in all 21 trials), renal function (18), HIV/AIDS status (17), performance status (16), history of other malignancies (16), hepatic function (16), and cardiac function (15), other serious health conditions (13), pregnancy status (10), neuro/psych function (10), age (10), metabolic disease status (9), CNS involvement (9), birth control (8), pulmonary function (8), WBC count (8), HBV status (8), platelet count (7), measurable disease (7), HCV status (7), active infection status (7), and CD20 status (7). We included 738 patients with newly diagnosed FL undergoing first-line therapy from MER and 703 patients from LEO. In MER, the median age was 60 years; 87% were White vs 2% non-White, 80% were non-Hispanic vs 2% Hispanic, and 68% were stage III/IV. In LEO, the median age was 60 years; 88% were White vs 11% non-White, 87% were non-Hispanic vs 11% Hispanic, and 67% were stage III/IV. Exclusion criteria impacting more than 10% of patients included stage (31 in LEO vs 29% in MER), self-reported serious health conditions (17 vs 31%), prior cancer diagnosis (14 vs 11%), performance status (10%), and platelet count (10%). Patients excluded due to the following criteria tended to be older: renal function (median 70 vs 60 years in MER), prior malignancy (67 vs 58 years), and self-reported serious health conditions (66 vs 58 years). This pattern was consistent in LEO (Table). No eligibility criteria significantly impacted race/ethnicity. Given the potential for multiple eligibility criteria to exclude the same patients, we used a step-wise approach to evaluate the impact of individual criteria on patients remaining after exclusion by the larger group of criteria, and whether liberalizing criteria impacted patient numbers and/or demographics. We found that only self-reported serious health conditions significantly impacted numbers (excluding 43% of patients), whereas hematologic parameters and performance status excluded only 5 and 1% of patients, respectively, with no impact on age or race/ethnicity. We also found that liberalizing stage requirement from III-IV to II-IV could increase enrollment by 14% in MER (12% in LEO), and liberalizing platelet requirement from ≥150,000 to ≥100,000 could increase enrollment by 11% (15% in LEO). Moreover, liberalizing eligibility criteria had no impact on age or race/ethnicity of the patient pool or on EFS (Figure). Conclusions: We found that excluding patients with prior malignancies, poor renal function, and self-reported serious health conditions appears to inadvertently exclude older patients. Other serious health conditions appeared to exclude a significant number of patients but did not impact patient demographics. Liberalizing certain criteria, including stage and platelet requirement, could potentially increase trial accrual, but would not likely correct the older patient deficit. These findings may serve in developing consensus eligibility criteria for future first-line FL trials. Figure 1 Figure 1. Disclosures Flowers: Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; National Cancer Institute: Research Funding; Allogene: Research Funding; Biopharma: Consultancy; Cellectis: Research Funding; EMD: Research Funding; Genentech/Roche: Consultancy, Research Funding; Epizyme, Inc.: Consultancy; Genmab: Consultancy; Iovance: Research Funding; Guardant: Research Funding; Burroughs Wellcome Fund: Research Funding; Sanofi: Research Funding; Takeda: Research Funding; Spectrum: Consultancy; Gilead: Consultancy, Research Funding; Amgen: Research Funding; Xencor: Research Funding; Nektar: Research Funding; SeaGen: Consultancy; Ziopharm: Research Funding; TG Therapeutics: Research Funding; 4D: Research Funding; Acerta: Research Funding; Denovo: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Morphosys: Research Funding; Adaptimmune: Research Funding; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; BeiGene: Consultancy; AbbVie: Consultancy, Research Funding; Kite: Research Funding; Janssen: Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; Pharmacyclics: Research Funding. Link: MEI: Consultancy; Novartis, Jannsen: Research Funding; Genentech/Roche: Consultancy, Research Funding. Friedberg: Acerta: Other: DSMC ; Bayer: Other: DSMC ; Novartis: Other: DSMC . Cohen: Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly: Research Funding; Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead: Consultancy. Kahl: AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding; AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy. Lossos: Lymphoma Research Foundation: Membership on an entity's Board of Directors or advisory committees; Stanford University: Patents & Royalties; Seattle Genetics: Consultancy; NCI: Research Funding; Verastem: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; NIH grants: Research Funding; University of Miami: Current Employment. Nastoupil: Bayer: Honoraria; Gilead/Kite: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; ADC Therapeutics: Honoraria; IGM Biosciences: Research Funding; Takeda: Honoraria, Other: DSMC, Research Funding; Janssen: Honoraria, Research Funding; Genentech: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; Denovo Pharma: Other: DSMC; Caribou Biosciences: Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; MorphoSys: Honoraria. Maurer: Nanostring: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; BMS: Research Funding. Cerhan: NanoString: Research Funding; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; Regeneron Genetics Center: Other: Research Collaboration; Genentech: Research Funding. Martin: ADCT: Consultancy.

Abstract Introduction: Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 Chimeric Antigen Receptor (CAR) T-cell therapy that induces durable responses in patients with relapsed or refractory large B-cell lymphoma. At a median of 27.1 months follow-up on the ZUMA-1 trial, median overall survival (OS) was 25.8 months with 39% progression free survival (PFS) at 2 years post-infusion (Locke, Lancet Onc 2019). We previously reported outcomes of axi-cel patients treated with standard of care therapy at a median follow up of 12.9 months, including 42% who did not meet eligibility criteria for ZUMA-1 based on co-morbidities (Nastoupil, JCO 2020). Here we report results from this cohort at a median follow up of 32.4 months, as well as late outcomes of interest including cytopenias, infections and secondary malignancies. Methods and Results: The US Lymphoma CAR-T Consortium comprised of 17 US academic centers who contributed data independent of the manufacturer. Two hundred and ninety-eight patients underwent leukapheresis with intent to manufacture standard of care axi-cel as of September 30, 2018. In infused patients (n=275), OS and PFS were calculated from date of infusion. After median follow-up of 32.4 months (95% CI 31.1 - 34.3), median OS was not reached (95% CI 25.6 - not evaluable) (Figure 1A) with 1-, 2- and 3-year OS of 68.5% (95% CI 62.6-73.7), 56.4% (95% CI 50.1-62.2) and 52.2% (95% CI 45.7-58.2%), respectively. Median PFS was 9 months (95% CI 5.9-19.6) (Figure 1B); 1-, 2- and 3-year PFS was 47.4% (95% CI 41.4-53.2), 41.6% (95% CI 35.6-47.5) and 37.3% (95% CI 31.3-43.2), respectively. Twenty-seven PFS events occurred at or after 1 year post infusion;19 events were progressive lymphoma, with the latest relapse observed 28 months after axi-cel infusion. Eight patients died while in remission from their lymphoma: 4 from secondary malignancy, 3 from infection, and 1 from unknown causes. Results of multivariable modeling were similar to our prior analysis: factors associated with both a shorter PFS and shorter OS included male sex, elevated pre-lymphodepletion LDH, and poor ECOG status. Complete blood count and B- and T-cell recovery data were collected at 1 and 2-years post-infusion, excluding patients who had relapsed or been treated for secondary malignancy at time of collection (Table 1). Rates of neutropenia (absolute neutrophil count ≤1000) at 1- and 2- years were 9.2% (10/109) and 11.2% (9/80) and rates of CD4 count ≤200/ul were 62% (23/37) and 27% (7/26). Recovery of B cells was seen in 54% (15/28) and 57% (13/23) at 1-and 2-years post infusion. Infections were reported in 31.2% (34/109) patients between 6- and 12-months post infusion, and 17% (18/109) were severe, requiring either hospitalization and/or IV antibiotics. Twenty-one patients (24%, 21/89) had an infection between 1- and 2- years, 11% of which were severe. Twenty percent (10/49) of patients between 2- and 3-years had an infection and 4 (8%) were severe. Neutropenia, low CD4 counts, and IgG levels were not associated with infection, though patients with infection between 6-12 months were more likely to have received IVIG (p<0.001). No patient in this cohort died of COVID-19. Twenty-two of 275 (8%) patients were diagnosed with subsequent malignancy after axi-cel treatment: 14/275 (5%) patients were diagnosed with myeloid malignancies (MDS (n=12), AML (n=1), CMML (n=1)); other malignancies included squamous cell carcinoma of skin (n=3); sarcoma (n=1); endometrial (n=1); lung (n=1); mesothelioma (n=1) and AITL (n=1). Patients with myeloid malignancy had a median age of 62 at axi-cel apheresis (IQR 56-67), 64% were male and median lines of prior therapy was 4 (IQR 3-6), including 36% with a prior autologous stem cell transplant. Eleven patients were in remission from lymphoma at myeloid malignancy diagnosis, while 3 were diagnosed after progression and interval therapy. Conclusion: This multi-center retrospective study showed similar long-term results to the ZUMA-1 trial, despite including patients who did not meet ZUMA-1 eligibility criteria based on comorbidities. Sixteen percent of PFS events were seen after 1 year, largely due to disease progression. Late infection was common but was not explained by persistent neutropenia or low CD4 counts. Subsequent malignancy, including MDS, occurred in 8% of patients and require further study to better identify patients at risk. J.Y.S and M.D.J contributed equally; S.D and M.L contributed equally. Figure 1 Figure 1. Disclosures Jain: BMS, Kite/Gilead, Novartis, Precision Biosciences, Takeda: Consultancy. Nastoupil: Pfizer: Honoraria, Research Funding; MorphoSys: Honoraria; Takeda: Honoraria, Other: DSMC, Research Funding; ADC Therapeutics: Honoraria; IGM Biosciences: Research Funding; Genentech: Honoraria, Research Funding; Epizyme: Honoraria, Research Funding; Caribou Biosciences: Research Funding; Gilead/Kite: Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding; Denovo Pharma: Other: DSMC; Bayer: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding. Ghobadi: Atara: Consultancy; Amgen: Consultancy, Research Funding; Wugen: Consultancy; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Lin: Gamida Cell: Consultancy; Juno: Consultancy; Merck: Research Funding; Bluebird Bio: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Research Funding; Sorrento: Consultancy; Legend: Consultancy; Takeda: Research Funding; Vineti: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. Reagan: Seagen: Research Funding; Kite, a Gilead Company: Consultancy; Genentech: Research Funding; Curis: Consultancy. Oluwole: Curio Science: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding. McGuirk: EcoR1 Capital: Consultancy; Gamida Cell: Research Funding; Bellicum Pharmaceuticals: Research Funding; Novartis: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Novartis: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astelllas Pharma: Research Funding; Pluristem Therapeutics: Research Funding; Fresenius Biotech: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding. Deol: Kite, a Gilead Company: Consultancy. Sehgal: Juno/Celgene: Research Funding; Kite/Gilead: Research Funding. Goy: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; LLC(Targeted Oncology): Consultancy; Xcenda: Consultancy, Honoraria; Xcenda: Consultancy; Acerta: Consultancy, Research Funding; AbbVie/Pharmacyclics: Consultancy, Honoraria, 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; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Gilead: Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Phamacyclics: Research Funding; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Michael J Hennessey Associates INC: Consultancy; Genentech/Hoffman la Roche: Research Funding; MorphoSys: Honoraria, Other; Karyopharm: Research Funding; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Incyte: Honoraria; Medscape: Consultancy; Novartis: Consultancy, Honoraria; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Infinity/Verastem: Research Funding; Rosewell Park: Consultancy; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; OncLive Peer Exchange: Honoraria; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Constellation: Research Funding; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Hill: Pfizer: Consultancy, Honoraria; Beigene: Consultancy, Honoraria, Research Funding; Gentenech: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Celgene (BMS): Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Andreadis: CRISPR Therapeutics: Research Funding; GenMAB: Research Funding; Novartis: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Epizyme: Honoraria; Incyte: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; Karyopharm: Honoraria; Atara: Consultancy, Honoraria; BMS: Research Funding; Merck: Research Funding. Muñoz: Seagen: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Kite, a Gilead Company: Consultancy, Speakers Bureau; Pfizer: Consultancy; Janssen: Consultancy, Speakers Bureau; Juno/Celgene: Consultancy; Bristol Myers Squibb: Consultancy; Alexion: Consultancy; BeiGene: Consultancy, Speakers Bureau; Fosunkite: Consultancy; Innovent: Consultancy; Debiopharma: Consultancy; Karyopharm: Consultancy; Genmab: Consultancy; ADC Therapeutics: Consultancy; Epizyme: Consultancy; Servier: Consultancy; Acrotech: Speakers Bureau; Verastem: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol Myers Squibb: Speakers Bureau; Genentech: Speakers Bureau; Aurobindo: Speakers Bureau; Physicians' Education Resource: Honoraria; Kyowa Kirin: Consultancy, Honoraria, Speakers Bureau; OncView: Honoraria; Targeted Oncology: Honoraria. Westin: AstraZeneca: Consultancy, Research Funding; 47 Inc: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Morphosys: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Umoja: Consultancy; Iksuda Therapeutics: Consultancy; MorphoSys: Consultancy, Research Funding; Curis: Research Funding; Genentech: Consultancy, Research Funding. Chavez: Bristol Myers Squibb: Speakers Bureau; Karyopharm Therapeutics: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Kite/Gilead: Consultancy; Abbvie: Consultancy; MorphoSys: Speakers Bureau; BeiGene: Speakers Bureau; Novartis: Consultancy; Adaptive: Research Funding; Epizyme: Speakers Bureau; AstraZeneca: Research Funding. Bennani: Kyowa Kirin: Other: Advisory Board; Daichii Sankyo Inc: Other: Advisory Board; Purdue Pharma: Other: Advisory Board; Verastem: Other: Advisory Board; Vividion: Consultancy, Other: Advisory Board. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Miklos: Pharmacyclics: Patents & Royalties; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy; Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; 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; 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. Locke: GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Umoja: Consultancy, Other; Cowen: Consultancy; EcoR1: Consultancy; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Legend Biotech: Consultancy, Other; Janssen: Consultancy, Other: Scientific Advisory Role; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role. Dahiya: Kite, a Gilead Company: Consultancy; Atara Biotherapeutics: Consultancy; Miltenyi Biotech: Research Funding; Jazz Pharmaceuticals: Research Funding; BMS: Consultancy. Lunning: Spectrum: Consultancy; AstraZeneca: Consultancy; Acrotech: Consultancy; Legend: Consultancy; Novartis: Consultancy; Kyowa Kirin: Consultancy; Karyopharm: Consultancy; Morphosys: Consultancy; TG Therapeutics: Consultancy; Janssen: Consultancy; AbbVie: Consultancy; Verastem: Consultancy; Myeloid Therapeutics: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; Daiichi-Sankyo: Consultancy; Beigene: Consultancy; ADC Therapeutics: Consultancy; Kite, a Gilead Company: Consultancy.

Background: With the incorporation of positron emission tomography (PET) imaging as part of the standard staging evaluation of follicular lymphoma (FL), it is generally recommended to obtain the diagnostic biopsy from a lesion with the highest standardized uptake value (SUV) to rule out de novo histologic transformation (HT). In some cases such an approach might be impractical, while in other cases a biopsy from a diseased area with a high SUV may still demonstrate an indolent histology. To date, there is no data to guide treatment choices in patients (pts) with FL with high SUVmax but with no documented evidence of HT. Specifically, it remains unclear whether anthracycline-containing regimens, such as R-CHOP, provide a better outcome than R-Bendamustine (BR). Furthermore, it is unknown whether rituximab (R) maintenance is beneficial in this setting. Therefore, we aimed to compare the efficacy of R-CHOP vs BR in newly diagnosed FL pts with high SUVmax at baseline PET and to clarify the role of maintenance. Patients and Methods: We retrospectively identified 261 consecutive pts with newly diagnosed biopsy-proven FL1-3A and a SUVmax≥13 on baseline PET, who were treated with frontline R-CHOP (n=183) or BR (n=78) at 7 US cancer centers based on the physician's choice. Progression-free survival (PFS) was calculated from starting treatment until progression, relapse or death. Cut-offs of SUVmax ≥13≤18 and SUVmax>18 were used for sub-analysis (Haematologica;2020;105:1907-1913). Results: Median age was 59 years. The baseline characteristics of the two groups differed significantly for a younger age (58 vs 62 years, p=0.009), a higher rate of B-symptoms (26% vs 10%, p=0.005) and baseline SUVmax>18 (49% vs 36%, p=0.04) in the R-CHOP group. A diagnostic biopsy was obtained from the site at the highest SUV in 129 (71%) and 43 (55%) pts, respectively (p=0.01). These suggest a potential selection of R-CHOP in pts with adverse features. At the end of therapy (EoT), R-CHOP treated pts achieved higher PET-CT complete response rates (CR 82% vs 69%, p=0.02). This superiority held in pts with diagnostic biopsy at the highest SUV site (CR 83% vs 67%, p=0.03), but not in the others (CR 80% vs 71%, p=0.37). Progression occurred at EoT in 11 and 14 pts receiving R-CHOP and BR (6% vs 18%, p=0.02), with a higher rate of HT in the BR group (13% vs 4%, p=0.006). After a median follow-up of 76 months (range, 4-208 months), there was no significant difference in PFS between R-CHOP and BR treated pts (hazard ratio [HR] 1.22, p=0.34). PFS was strongly associated with FLIPI 2 (HR 2.32, p=0.01) and 3-5 (HR 2.69, p=0.003) in the univariate as well as in the multivariate analysis (FLIPI 2 HR 2.19, p=0.02; FLIPI 3-5 HR 2.51, p=0.01). There was a trend toward overall survival (OS) benefit in the R-CHOP group (Fig.1A). In the univariate analysis for OS, BR regimen (HR 2.12, p=0.03), age >60 (HR 2.54, p=0.006), FLIPI 3-5 (HR 5.13, p=0.03) and biopsy at the highest SUV site (HR 0.44, p=0.01) were prognostic, however none of those remained significant in the multivariate analysis (BR regimen HR 1.84, p=0.09; age >60 HR 1.92, p=0.08; FLIPI 3-5 HR 3.11, p=0.14; biopsy at the highest SUV site HR 0.60, p=0.13; SUVmax>18 HR 1.87, p=0.055). Among pts with EoT response after R-CHOP or BR (n=170 and n=64, respectively), one third in each group (36% vs 41%, respectively) received R-maintenance for a median of 8 administrations (range, 2-12). A significant PFS advantage (landmark analysis) was observed with R-maintenance (Fig.1B; HR 0.53, p=0.02); however, this did not translate in survival benefit (HR 0.67, p=0.49). In a multivariable model, R-maintenance (HR 0.53, p=0.02), FLIPI 2 (HR 2.47, p=0.03) and 3-5 (HR 2.79, p=0.01) remained independent prognosticators of PFS, while no parameters significantly affected OS. The 2-year HT rate (10% vs 17%) and cumulative incidence did not statistically differ between R-CHOP and BR groups (Fig.1C, p=0.159). Early progression (POD24) occurred in 43 and 22 pts who received R-CHOP and BR, respectively (24% vs 28%) and resulted in a significantly higher risk of death (HR 4.12, p=0.006). Conclusion: In newly diagnosed FL pts with SUVmax≥13 at baseline PET, R-CHOP was more effective in achieving CR and reducing the risk of early HT compared with BR, and it was associated with a trend toward survival advantage. Rituximab maintenance significantly prolonged PFS. A prospective evaluation with a larger population will be needed to confirm our findings. Disclosures Joffe: Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Ruella:Abclon, BMS, NanoString: Consultancy; Abclon: Consultancy, Research Funding; UPenn/Novartis: Patents & Royalties. Svoboda:Adaptive: Consultancy; Astra-Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Imbrium: Consultancy; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding; TG: Research Funding; Genmab: Consultancy; Atara: Consultancy. Witzig:Immune Design: Research Funding; Spectrum: Consultancy; Karyopharm Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; AbbVie: Consultancy; MorphSys: Consultancy; Incyte: Consultancy. Smith:TG Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Celgene: Consultancy, Research Funding; Pharmacyclics: Research Funding; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Armand:Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; IGM: Research Funding; Infinity: Consultancy; Genentech: Research Funding; Sigma Tau: Research Funding; Celgene: Consultancy; Adaptive: Consultancy, Research Funding; Tensha: Research Funding; Roche: Research Funding; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy. Nastoupil:Janssen: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Gilead/KITE: Honoraria; Gamida Cell: Honoraria; TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Novartis: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Ansell:Takeda: Research Funding; Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; AI Therapeutics: Research Funding; ADC Therapeutics: Research Funding. Zelenetz:Novartis: Consultancy; Adaptive Biotechnology: Consultancy; Genentech/Roche: Consultancy; Gilead: Consultancy; Gilead: Research Funding; Celgene: Consultancy; Roche: Research Funding; Amgen: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Sandoz: Research Funding; Celgene: Research Funding; MorphoSys: Research Funding; MEI Pharma: Research Funding. Younes:BioPath, Xynomic, Epizyme, and F. Hoffmann-La Roche: Consultancy; Janssen, Curis, Merck, Bristol-Myers Squibb, Syndax Pharmaceuticals, F. Hoffmann-La Roche, Curis (Inst), Johnson & Johnson (Inst), Novartis (Inst): Research Funding; Janssen, AbbVie, Merck, Curis, Epizyme, F. Hoffmann-La Roche, Takeda, Bristol-Myers Squibb, Bayer HealthCare Pharmaceuticals, Celgene, Incyte, Janssen Pharmaceuticals, Merck, Sanofi, Seattle Genetics, Takeda Millennium: Honoraria; AstraZeneca: Current Employment; MSKCC: Ended employment in the past 24 months.

8017 Background: LAM-002 is a selective inhibitor of PIKfyve that disrupts lysosomal homeostasis, inducing cytotoxicity in B-cell lymphoma models as monotherapy or with anti-CD20 or anti-PDL1 antibodies (Gayle et al., Blood 2017;129(13):1768). Methods: In this study, patients received LAM-002 orally 2-3 times per day (BID or TID) in a 3+3 escalation. Additional patients received LAM-002 125 mg BID as monotherapy; with rituximab 375 mg/m2 intravenously (IV) and or subcutaneously weekly (Q1W) x 4 → Q8W x 4; or atezolizumab 1200 mg IV Q3W until disease progression or unacceptable toxicity. Pharmacokinetics (PK) were assessed for 8 hours postdose on Days 1 and 8. Efficacy was evaluated Q6-12W. Results: The study enrolled 62 patients (M:F n = 32/30); median [range] age = 69 [46-89] years; with diagnoses (n) of diffuse large B-cell lymphoma (25), follicular lymphoma (19), marginal zone lymphoma (8), mantle cell lymphoma (5), or chronic lymphocytic leukemia (5) to receive LAM-002 alone (n) at 50 mg BID (3), 100 mg BID (8), 150 mg BID (8), 75 mg TID (4), or 125 mg BID (20); LAM-002/rituximab (12); or LAM-002/atezolizumab (7). During LAM-002 dose-ranging (50 mg BID → 100 mg BID → 150 mg BID → 75 mg TID → 125 mg BID) transient, reversible nausea and/or diarrhea occurred at 150 mg BID and 75 mg TID, resulting in a LAM-002 recommended Phase 2 dosing regimen (RP2DR) of 125 mg BID. Among 39 patients receiving LAM-002, 125 mg BID, alone or in combination for up to 22 cycles (1.9 years), adverse events were typically low-grade. LAM-002 PK showed rapid absorption, dose proportionality, minimal accumulation, and no substantive changes with rituximab or atezolizumab coadministration. In patients with follicular lymphoma and median [range] prior therapies = 3 [1-9] treated with the RP2DR, objective response rates were 2/7 (29%; 1 complete response [CR], 1 partial response [PR]) with LAM-002, 5/8 (63%; 1 CR, 4 PRs) with LAM-002/rituximab, and 2/2 (100%; 2 PRs) with LAM-002/atezolizumab. Conclusions: LAM-002, the first clinical PIKfyve inhibitor, is safe alone or with full-dose anti-CD20 or anti-PD-L1 inhibition. LAM-002 does not cause the myelosuppressive or immune adverse events associated with lenalidomide or PI3K inhibitors. Promising efficacy supports registration-directed Phase 2/3 testing of LAM-002 monotherapy and combination therapy for patients with previously treated follicular lymphoma. Clinical trial information: NCT02594384 .

PURPOSE Axicabtagene ciloleucel (axi-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory large B-cell lymphoma (LBCL) on the basis of the single-arm phase II ZUMA-1 trial, which showed best overall and complete response rates in infused patients of 83% and 58%, respectively. We report clinical outcomes with axi-cel in the standard-of-care (SOC) setting for the approved indication. PATIENTS AND METHODS Data were collected retrospectively from all patients with relapsed/refractory LBCL who underwent leukapheresis as of September 30, 2018, at 17 US institutions with the intent to receive SOC axi-cel. Toxicities were graded and managed according to each institution’s guidelines. Responses were assessed as per Lugano 2014 classification. RESULTS Of 298 patients who underwent leukapheresis, 275 (92%) received axi-cel therapy. Compared with the registrational ZUMA-1 trial, 129 patients (43%) in this SOC study would not have met ZUMA-1 eligibility criteria because of comorbidities at the time of leukapheresis. Among the axi-cel–treated patients, grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 7% and 31%, respectively. Nonrelapse mortality was 4.4%. Best overall and complete response rates in infused patients were 82% (95% CI, 77% to 86%) and 64% (95% CI, 58% to 69%), respectively. At a median follow-up of 12.9 months from the time of CAR T-cell infusion, median progression-free survival was 8.3 months (95% CI, 6.0 to15.1 months), and median overall survival was not reached. Patients with poor Eastern Cooperative Oncology Group performance status of 2-4 and elevated lactate dehydrogenase had shorter progression-free and overall survival on univariable and multivariable analysis. CONCLUSION The safety and efficacy of axi-cel in the SOC setting in patients with relapsed/refractory LBCL was comparable to the registrational ZUMA-1 trial.

7517 Background: Axi-cel, an anti-CD19 CART cell therapy, achieved 83% ORR, 58% CR rate, with 39% PFS at 2 years in patients (pts) with relapsed refractory large B-cell lymphoma (LBCL) on the ZUMA-1 study (Locke, Lancet Oncology 2018). Data from a 17-center consortium showed response rates were similar in 274 pts treated with commercial axi-cel (Nastoupil, ASH 2018). Here, we performed retrospective analysis of outcomes in pts with progressive disease (PD) after axi-cel. Methods: Response status was determined by Cheson 2014 and reported as date of radiologic relapse. 274 pts were infused by December 26, 2018 with maximum follow-up of 14 months; 116 pts had PD as of Feb 1, 2019. Twelve sites provided additional data, detailing 85% of PD pts (n=99) with a median time to relapse of 54 days (IQR 16-120). Results: Pre axi-cel pt characteristics: median lines of therapy were 4 (range 2-11), 86% were Stage III/IV and 22% were ECOG >1. Following relapse, 60% (n=61) were biopsied and 70% (43/61) had CD19 expression measured. Thirty percent (13/43) were CD19 negative by: IHC (3/13), flow (2/13) or both (8/13). Seventy percent (n=71) received salvage therapy for PD. Median lines of salvage therapy was 1 (range 0-4). The most common therapies were Lenalidomide-based (30%), checkpoint inhibitors (30%), chemotherapy (20%) and radiation (10%). First salvage therapy ORR by regimen: checkpoint inhibitors = 24%, lenalidomide regimens = 20% and chemotherapy = 11%. One patient received allogeneic transplant. Twelve pts enrolled on clinical trial, with one receiving 2nd CAR-T. Median OS following relapse was 108 days (95% LCL 71). Nineteen pts relapsed <3 months after axi-cel and did not receive therapy with median OS 17 days (95% CI 7-49); 33 pts relapsed <3 months and received therapy with 114 day median OS (95% LCL 82). In contrast, 30 pts who relapsed >3 months post axi-cel and received therapy had estimated median OS >220 days (95% LCL 81). Conclusions: Patients with LBCL relapsing less than 3 months following axi-cel have extremely poor outcomes supporting the development of novel therapies. Therapy for relapse >3 months appears promising. JYS and SD contributed equally; APR, DBM and BTH contributed equally.

Introduction. The VES-13 is a simple, self-reported, function based tool originally developed to screen community-dwelling populations to identify persons age 65 years and older at risk of death and functional decline, including death in the next 12 months. The VES-13 items include patient's age, self-rated overall health status, functional limitations in physical activity, and functional disabilities in more complex activities of daily living. As part of the Lymphoma Epidemiology of Outcomes (LEO) cohort study, we collected self-reported VES-13 data at study enrollment on all participants regardless of age, and here we report on the prevalence of vulnerable status defined by the VES-13 and its association with 1-year mortality, overall, stratified at age 65 years, and in the subset of diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy. Methods. From 7/2015 to 6/2017, 3253 participants with NHL were enrolled within 6 months of their diagnosis into the LEO cohort. 2004 were evaluable on VES-13, and 1183 (59%) completed it before the initiation of therapy. VES-13 scores range from a minimum of 0 (low risk for decline) to a maximum of 10 (greatest risk for decline), and a score ≥3 was classified as vulnerable. Clinical, pathology and treatment data were abstracted using a standard protocol, and participants were contacted every 6 months for the first three years and then annually thereafter to identify outcomes. Medical records were reviewed by LEO clinicians to classify cause of death according to a standard protocol. Therapy was determined by the treating physician, and this was independent of knowledge of the VES-13 score. The association of VES-13 with 1-year mortality from date of diagnosis was estimated using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression models, which also provided model c-statistics. Results. The median age of the 2004 participants in this analysis was 62 years (range 18-94); 57% were male; 54% were ≥65 years; and 28% had a normal body mass index (BMI), 1% were underweight, 35% were overweight, and 36% were obese. Clinically, 59% of participants had an aggressive subtype, 65% were stage III-IV, 24% had B-symptoms, and 11% had a performance status (PS) of ≥2. Overall, 28% of participants were classified as vulnerable (95% CI 26%-30%), with a higher prevalence among those completing the survey after initiation of therapy (38%, 95% 34%-41%) versus before initiation of therapy (22%, 95% CI 20%-24%), and a higher prevalence for those ≥65 years (32%, 95% CI 29%-34%) versus &lt;65 (25%, 95% CI 22%-28%). During the first year of follow-up, there were 147 deaths, with 61% due to lymphoma, 14% therapy-related, 12% due to another malignancy, 3% other causes, and 10% unknown. Significant univariate predictors of 1-year mortality included vulnerable status, older age, PS 2+, stage III-IV, aggressive subtype, lower quality of life score, lower BMI, and 1 or more comorbidities, and were included the backward stepwise modeling. Vulnerable status (OR=3.26, 95% CI 2.15-4.96) was retained in the final model that also included age, PS, stage, and NHL subtype (Table), with a model c-statistic of 0.81. As shown in the Table, these associations were similar whether VES-13 was assessed before (c-statistic 0.77) or after (c-statistic 0.81) initiation of therapy. After adjustment for age, PS, stage and NHL subtype, vulnerable status predicted 1-year mortality in participants ≥65 years (OR=1.96, 95% CI 1.15-3.36; model c-statistic 0.80) as well as &lt;65 years (OR=6.38, 95% CI 3.07-13.3; model c-statistic 0.83). Finally, in the DLBCL patients treated with immunochemotherapy (N=521), vulnerable status (38% of patients) also predicted 1-year mortality (OR=2.11, 95% CI 1.05-4.26) after adjusting for age, PS and stage (model c-statistic 0.78). Conclusion. Based on a self-administered VES-13, 28% of newly diagnosed NHL patients in the LEO cohort were classified as vulnerable, including 25% of those &lt;65 years, and vulnerable status was a strong predictor of 1-year-mortality, even in the subset of DLBCL patients treated with presumed curative intent. These results highlight the potential value of screening for vulnerable status overall and across a wider age spectrum in order to optimize patient management and reduce early mortality. Disclosures Martin: Karyopharm: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Teneobio: Consultancy. Casulo:Gilead: Honoraria, Other: Travel, accommodation, expenses; Celgene: Research Funding; Roche: Other: Travel, accommodation, expenses. Cohen:Takeda Pharmaceuticals North America, Inc.: Research Funding; Bristol-Meyers Squibb Company: Research Funding; Hutchison: Research Funding; Astra Zeneca: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; UNUM: Research Funding; Gilead/Kite: Consultancy; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding. Farooq:Kite Pharma: Research Funding; Celgene: Honoraria. Friedberg:Acerta: Other: Data & Safety Monitoring Committee; Bayer: Honoraria, Other: Data & Safety Monitoring Committee. Kahl:Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Consultancy; TG Therapeutics: Consultancy. Lossos:Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Maurer:Nanostring: Research Funding; Celgene: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees. Nastoupil:Spectrum: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; Novartis: Honoraria; TG Therapeutics: Honoraria, Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding. Rutherford:Heron: Consultancy, Honoraria; Janssen Scientific Affairs: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Juno Therapeutics Inc: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees. Flowers:National Cancer Institute: Research Funding; BeiGene: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Bayer: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; Acerta: Research Funding; TG Therapeutics: Research Funding; Millenium/Takeda: Research Funding; AstraZeneca: Consultancy; Optimum Rx: Consultancy; V Foundation: Research Funding; Celgene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Denovo Biopharma: Consultancy; Gilead: Consultancy, Research Funding. Cerhan:NanoString: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding.

Introduction: Axicabtagene Ciloleucel (axi-cel), a CD19 chimeric antigen receptor (CAR) T-cell therapy, was approved for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin lymphoma in October, 2017. In the ZUMA-1 trial leading to axi-cel FDA approval, patients (pts) with prior or active secondary central nervous system (CNS) lymphoma involvement were excluded. A recent publication of 8 pts with secondary CNS lymphoma who underwent Tisagenlecleucel CAR T cell therapy was reported (Frigault M.J.2019). Since the two FDA approved CAR T cell products have a different neurotoxicity profile, understanding outcomes of axi-cel in this setting is important. We report here the real-world experience of 17 pts treated with axi-cel who had a history of secondary CNS involvement or had active CNS disease at time of CAR T infusion. Methods: Seventeen academic centers from the US Lymphoma CAR T Consortium contributed data independently from the manufacturer. Data regarding secondary CNS involvement, management, and outcome were obtained in addition to CAR T therapy outcome for pts who were identified as having active, secondary CNS involvement at the time of evaluation for CAR-T therapy. Nine centers reported data on 17 cases with CNS involvement. Follow-up data was missing for one pt in the CNS cohort. Lee criteria or the modified Lee grading scale were used for cytokine release syndrome (CRS). CTCAEv4 or CARTOX grading were used for immune effector cells associated neurotoxicity syndrome (ICANS). All leukapheresed pts were included in the intention to treat (ITT) analysis for response rate and event-free survival (EFS). EFS was defined as date of leukapheresis until progression or death due to any cause. EFS was evaluated using Kaplan Meier curves with log-rank test. Differences in clinical characteristics and response between CNS and non-CNS pts were not formally tested due to small sample size and multiple comparison concerns. Results: With a data cut-off of 4/30/2019, 300 pts underwent leukapheresis with intention to manufacture standard of care axi-cel. By the time of leukapheresis, 17 (6%) had secondary CNS involvement (4 parenchymal disease, 10 leptomeningeal/CSF, 3 data not available). Compared to the non-CNS cohort, baseline demographics were comparable (Panel A). Manufactured axi-cel was within specification for 100% of the CNS cohort. There was a higher rate of bridging therapy use in the CNS cohort 82% (1 steroids only, 2 radiation therapy, 12 systemic therapy) vs 52% in non-CNS cohort; p=0.022. Time from leukapheresis to CAR T infusion was 3.5 days longer in the CNS cohort as opposed to the non-CNS cohort: median time of 29.5 (range 20-76) vs. 26 days (range 5-67), (p=0.029), respectively. The CAR T infusion rate was 88% for the CNS cohort (15/17) compared to 93% (262/283) in the non-CNS cohort. Among the 15 infused pts in the CNS cohort, 10 had resolution of CNS involvement, and 5 had persistent active CNS disease at time of CAR T infusion. After axi-cel infusion, the incidence of CRS and ICANS, of any grade or grade 3 or higher, were comparable between the CNS and non-CNS cohorts. Tocilizumab and steroid use were comparable between the two groups (Panel B). No seizures or cerebral edema were noted in the CNS cohort. With a median follow-up of 10.1 months from leukapheresis (range 7.6-12.6), the ITT best overall response rates (CR+PR) and ongoing responses at month 6 between CNS and non-CNS cohorts were 75% vs. 59%, and 41% vs. 31%, respectively (Panel B). In the 5 pts with active CNS disease at time of CAR T infusion, the response of CNS disease were 2 CR, 1 PR and 2 PD as best response. In the 10 pts with resolved CNS disease at time of CAR T infusion, 2 PD were seen and both occurred systemically. EFS from leukapheresis was not statistically significantly different between CNS and non-CNS cohorts (6 months EFS: CNS cohort, 36%; non-CNS cohort 57%. HR=1.58, 95% CI: 0.83-3.01, p=0.16, Panel C). Six month EFS from the date of infusion for the CNS cohort was 49.9% (Panel D). Conclusions: Pts attempting CAR T therapy with secondary CNS disease in the real world setting had similar rates of CAR T infusion, toxicity, and outcomes when compared to patients without CNS disease. Small sample size and limited follow-up caution the strength of conclusions for application to clinical practice, but these results support further investigation of CAR T in pts with history of or active secondary CNS lymphoma. Figure Disclosures Bennani: Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board. Maurer:Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees. Nastoupil:Bayer: Honoraria; Spectrum: Honoraria; TG Therapeutics: Honoraria, Research Funding; Novartis: Honoraria; Janssen: Honoraria, Research Funding; Gilead: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Jain:Kite/Gilead: Consultancy. Chavez:Novartis: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Cashen:Seattle Genetics: Other: Speaker's Bureau; Novartis: Other: Speaker's Bureau; Celgene: Other: Speaker's Bureau. Reagan:Kite, A Gilead Company: Consultancy; Curis: Consultancy; Seattle Genetics: Research Funding. Oluwole:Pfizer: Consultancy; Spectrum: Consultancy; Gilead Sciences: Consultancy; Bayer: Consultancy. McGuirk:Novartis: Research Funding; Fresenius Biotech: Research Funding; Astellas: Research Funding; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; ArticulateScience LLC: Other: Assistance with manuscript preparation; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Deol:Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board. Sehgal:Juno/Celgene: Research Funding; Merck: Research Funding; Kite/Gilead: Research Funding. Goy:COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: leadership role for profit healthcare company; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Astrazenca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; University of Nebraska: Research Funding; Hakensackumc: Research Funding; Takeda: Other: Grants outside of the submitted work; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work; Pharmacyclics/Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding; Genentech: Other: Grants outside of the submitted work, Research Funding; Hackensack University Medical Center, RCCA: Employment; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding. Hill:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG therapeutics: Research Funding; AstraZeneca: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Takeda: Research Funding; Amgen: Research Funding. Vu:Celgene: Other: Stock. Andreadis:Genentech: Equity Ownership, Other: Spouse is Employee; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy. Munoz:Incyte: Research Funding; Portola: Research Funding; Celgene: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Kite Pharma: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Fosunkite: Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau. Vose:Acerta Pharma: Honoraria, Other: Grants, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Celgene Corporation: Research Funding; Incyte Corporation: Research Funding; Kite Pharma: Honoraria, Other: Grants, Research Funding; Novartis: Research Funding; Seattle Genetics: Research Funding; AbbVie: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Legend Pharmaceuticals: Honoraria. Miklos:Miltenyi Biotech: Membership on an entity's Board of Directors or advisory committees; Becton Dickinson: Research Funding; AlloGene: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Locke:Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy. Neelapu:Unum Therapeutics: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Consultancy; Incyte: Consultancy; Poseida: Research Funding; Allogene: Consultancy; Merck: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Karus: Research Funding; Precision Biosciences: Consultancy; Cell Medica: Consultancy; Acerta: Research Funding; Cellectis: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy. Lin:Novartis: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; BlueBird Bio: Research Funding; Celgene: 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; Sorrento: Membership on an entity's Board of Directors or advisory committees.