ALBERT

Description: Background: Fever is a cardinal symptom of cytokine release syndrome (CRS) after CAR T-cell therapy with 84% of patients experiencing fever on the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel). Knowledge of the patterns of fever and associated symptoms may inform the clinical management of these patients. Methods: We performed a single center retrospective study in 78 patients receiving axi-cel for large B cell lymphoma (LBCL) as of 12/31/2018. We evaluated all the patients who developed fever during lymphodepleting chemotherapy with fludarabine (Flu) and cyclophosphamide (Cy), after CAR T-cell infusion, and after administration of tocilizumab (toci); and analyzed the association of fever with toxicity rates (grade 3+ CRS and neurotoxicity) and efficacy [overall response rates (ORR) and complete response (CR) rate 6 months post CAR T-cell infusion]. Fever was defined per the Lee criteria [equal to or greater than 38 °C], CRS used the modified Lee criteria and neurotoxicity used the CARTOX grading system. Results: Fever occurred in 71/78 (91%) of patients. Rates of grade 3+ CRS and neurotoxicity were 9% (7/78) and 26% (20/78) respectively. The CR rate at 6 months was 41% (32/78). Toxicities and outcomes in patients with the described fever characteristics are shown in the Table. During lymphodepletion with Flu/Cy, fever was observed in 11% (9/78) of patients. Fever occurred within 24 hours of axi-cel infusion in 47% (37/78) and within 72 hours of axi-cel infusion in 71% (55/78) of the patients. In total, 41% (32/78) of patients were treated with anti-IL6R therapy (tocilizumab; toci) for CAR T toxicity. After the first dose of toci, fever recurred in 69% of patients (22/32), of which 34% (11/32) experienced fever recurrence within 24 hours of toci infusion. Conclusions: This is the first study to our knowledge that describes in detail the characteristics of fever after CAR T-cell therapy with axi-cel. Fever was common and occurred in 71% of the patients within 72 hours of axi-cel infusion. When toci was used, fever recurred in a majority of patients (69%) and in 1/3 of patients the fever recurred within 24 hours of toci infusion. These descriptive data may be used by clinicians to inform their expectations of fever occurring after treatment with axi-cel and/or toci. Table Disclosures Bachmeier: Kite/Gilead: Speakers Bureau. Chavez:Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals, Inc.: Speakers Bureau. Shah:AstraZeneca: Honoraria; Novartis: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Pinilla Ibarz:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Sanofi: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Bayer: Speakers Bureau; TG Therapeutics: Consultancy; Teva: Consultancy; Janssen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding. Lazaryan:Kadmon: Consultancy. Davila:Bellicum: Consultancy; Anixa: Consultancy; GlaxoSmithKline: Consultancy; Precision Biosciences: Consultancy; Novartis: Research Funding; Adaptive: Consultancy; Celgene: Research Funding; Atara: Research Funding. Locke:Cellular BioMedicine Group Inc.: Consultancy; Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor. Jain:Kite/Gilead: Consultancy.

Description: Background: Recent data have shown that pre-transplant FDG-PET is prognostic in DLBCL patients undergoing autologous stem cell transplantation (ASCT). We retrospectively analyzed data on patients with DLBCL treated with ASCT to assess the impact of pre-transplant FDG-PET on relapse-free survival (RFS) and overall survival (OS). Methods: We reviewed medical records of 32 patients with DLBCL who underwent ASCT using high dose busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP) at Cleveland Clinic from June 2008 to December 2012 and had both a relapse FDG-PET as well as a pre-transplant FDG-PET available for review. All images were interpreted by a staff nuclear medicine radiologist blinded to the outcomes. Visual analysis was performed using the Deauville five-point scale and semiquantitative analysis was done by measuring the maximum standardized uptake value (SUVmax). ΔSUVmax was calculated by determining the difference between the SUVmax at the time of relapse and the SUVmax immediately prior to transplant. Patients were grouped into pre-transplant Deauville score 1-3 or 4-5. Baseline characteristics were compared between groups using the Chi-square test or Wilcoxon rank test. Cox proportional hazards analysis was used to identify prognostic factors. Outcomes were calculated from the date of ASCT. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test Results: The median age of the patients at transplant was 57 and 69% were male. There was no significant difference in baseline characteristics of patients who had a Deauville score 1-3 compared to patients who had a Deauville score 4-5 including mean age, gender, race, Karnofsky performance status, number of prior chemotherapy regimens, prior radiation therapy, and IPI at diagnosis and transplant. There was a trend towards significance in the median SUVmax at relapse in the Deauville 1-3 group compared to the Deauville 4-5 group (11.1 vs. 18.1, p=0.08) and a significant difference in the median pre-transplant SUVmax (2.3 vs. 8.1, p6 vs. 6) prior to transplant is predictive of poor RFS. Pre-transplant PET is a powerful tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies. Figure 1. OS of DLBCL patients undergoing ASCT based on pre-transplant Deauville score. Figure 1. OS of DLBCL patients undergoing ASCT based on pre-transplant Deauville score. Figure 2. RFS of DLBCL patients undergoing ASCT based on pre-transplant SUVmax. Figure 2. RFS of DLBCL patients undergoing ASCT based on pre-transplant SUVmax. Disclosures Smith: celegene, spectrum, genentech: Honoraria. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Description: Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P

Description: INTRODUCTION: High dose busulfan (Bu) is an integral component of many commonly-used preparative regimens for both allogeneic and autologous transplantation. Data on the efficacy and toxicity of q6 vs. q24 hour dosing are of significant clinical interest. In order to facilitate a therapeutic dose-monitoring protocol, we transitioned from q6 to q24 Bu dosing as part of our standard Bu/Cy/VP ASCT preparative regimen for patients with Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL) in July 2012. We present comparative outcomes of q24 Bu dosing vs historical controls receiving q6 Bu. METHODS We retrospectively reviewed 400 consecutive eligible lymphoma patients who underwent ASCT from 2007-2013 with Bu/Cy/VP. All patients received Cy 60 mg/kg IV over 4 hours on days -3 and -2 and VP 60 mg/kg as continuous infusion on days -5 and -4. Bu was given at a dose of either 0.8 mg/kg q6 (N = 307) x 14 doses for patients transplanted between 2007-July, 2012 or 2.8 mg/kg q 24 hours (N = 93) on days -9 through -6 for subsequent patients. Outcomes assessed from date of transplant were: relapse, non-relapse mortality (NRM), relapse-free survival (RFS) and overall survival (OS). Toxicity was assessed using pulmonary and liver function tests (PFTs and LFTs) at specified time-points before and after ASCT. In addition, for a subset of 22 patients receiving q24 Bu, we measured serial Bu serum levels after the first dose of Bu with an in-house liquid chromatography-tandem mass spectrometry assay using turbulent flow online extraction technology (Bunch, et al. J Chromatogr B Analyt Technol Biomed Life Sci, 2010. 878(31): p. 3255-8) and subsequently determined the cumulative Bu area-under the curve (AUC). RESULTS Baseline patient and disease characteristics of patients dosed with q6 and q24 Bu were similar. The median age was 55 (range 20-78) years; 63% were males. 18% had HL and 82% had NHL with a comparable distribution of subtypes in both groups. Patients in both groups had comparable rates of prior chemotherapy regimens and of complete/partial remission at the time of ASCT. Due to a change in institutional guidelines, plerixafor was more commonly incorporated in peripheral blood stem cell mobilization regimen in the q24 group compared to q6 cohort (70% vs. 39%, P

Description: Allogeneic HCT is a potentially curative but high risk therapy for patients with hematologic malignancies. HCT recipients are typically followed closely by their transplant center within the first 100 days, and with advances in supportive care, day 100 survival has continued to improve significantly over time. Longer term survival, however, remains a challenge and the factors that predict for later mortality are not well understood. We thus undertook this retrospective analysis to identify prognostic factors for 1-and 2-year survival among day 100 survivors. Of 413 patients that underwent a first allogeneic HCT from 2006 to 2014, 355 survived 〉100 days post-transplant. Diagnoses included acute myeloid leukemia (N=163), myelodysplastic syndrome (N=89), acute lymphoblastic leukemia (N=62), chronic myeloid leukemia (N=34), or undifferentiated/biphenotypic leukemia (N=7). 34% of patients had high risk, 18% intermediate, and 48% low risk disease by American Society for Blood and Marrow Transplantation (ASBMT) RFI risk category. Median age at transplant was 50 years (range, 18-73). The majority of patients were Caucasian (89.6%). Median household income was $49,980 (range 13,316-112,530) and median distance from transplant center was 46 miles (range, 1-1055). 40% patients had a high HCT co-morbidity index, 32% intermediate and 28% low. 152 (43%) patients underwent a matched related donor, 148 (42%) matched unrelated donor, 36 (10%) umbilical cord blood (UCB), 13 (3%) haplo-identical, and 6 (2%) mismatched unrelated donor transplants. The majority of patients (75%) underwent a myeloablative transplant and bone marrow (BM) (53%) was the primary graft source. Cox proportional hazards was used to identify prognostic variables for 1- and 2-year mortality in the 355 surviving patients using baseline characteristics and factors evaluated at day 100. Baseline characteristics as described above included patient, disease, transplant, and socioeconomic/psychosocial factors. Additional variables evaluated at day 100 included number of readmissions, days hospitalized, GVHD rates, infections, relapse within the first 100 days of transplant, and QOL measures as assessed by the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT), scored at baseline and day 100. 1- and 2-year mortality was 71%, and 54%, respectively, compared to a day 100 mortality of 86%. Among day 100 survivors, the most common causes of death within the first 2 years were relapse (N=78, 54%), followed by infection (N=24, 17%), pulmonary or other organ failure (N=23, 16%), and GVHD (N=16, 11%). In multivariable analysis evaluating risk factors for mortality among the day 100 survivors, lower income (HR 1.25, P=0.013), high risk ASBMT RFI (HR 1.75, P=0.03), relapse (HR 7.84, P

Description: Healthcare disparities, such as race/ethnicity and SES, can impact access to care and outcomes in cancer patients. ASCT is standard therapy for high-risk relapsed and refractory lymphoma, but is a highly specialized and resource-intensive procedure. The association of race and SES with outcomes in lymphoma patients undergoing ASCT has not been described previously. We conducted a retrospective cohort study of 687 consecutive ASCT recipients with Hodgkins (N=154, 22%) and non-Hodgkins (N=533, 78%) lymphoma transplanted between 2003 and 2013 at our institution. Zip code of residence was used to obtain median annual household income based on 2010 US Census data. Patients were categorized into low SES (1/KPS 1 year, however, mortality in the low SES group in primarily mediated through non-relapse causes. Our study highlights the need for active interventions to mitigate health care disparities in this high risk population. Table. 5-year outcomes after ASCT for lymphoma by SES Outcomes All patients, N=687 1-yr survivors, N=551 Low SES High SES P-value Low SES High SES P-value Relapse mortality 29% 25% 0.03 16% 18% 0.53 NRM 16% 12% 0.18 14% 9% 0.07 OS 55% 64% 0.004 70% 74% 0.07 PFS 41% 47% 0.01 57% 58% 0.25 Figure 1. OS for all patients and 1-year survivors Figure 1. OS for all patients and 1-year survivors Figure 2. Figure 2. Disclosures Hill: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Description: Background: Bortezomib (bort), lenalidomide (len), cyclophosphamide (cy), and dexamethasone (dex) combinations are acceptable initial treatment options for multiple myeloma (MM). At least 2 of these agents are generally used in initial treatment. Continuous len /dex treatment in older patients (pts) may be superior to shorter courses of 3 drug therapy (Benboubker L et al. N Engl J Med 2014; 371:906-917). Standardized treatment programs for cancer pts are important in a changing healthcare reimbursement system. Response adapted therapy for multiple myeloma has the potential to reduce toxicity, limit multi-drug resistant subclone development thus improving survival, and provide cost savings. Methods: The Cleveland Clinic multiple myeloma carepath initiates 2 drug response adapted therapy with len/dex (bort/dex if there is evidence of myeloma related kidney disease or unacceptable len cost to pt). This is an update to preliminary data of Narkhede et al 2014 ASH abstract 2620. Response assessment per current IMWG criteria is obtained with each cycle of therapy, although bone marrow biopsy is not required to confirm complete response. Pts with progressive disease (PD) after one cycle or lack of partial response (PR) after 2 cycles have either bort or len added to the initial 2 drug therapy. If needed, sequential addition of cy and liposomal doxorubicin occurs until at least PR is obtained. Pts achieving PR after 2 cycles are continued on 2 drug therapy. All transplant eligible pts are offered high dose melphalan and autologous stem cell transplant if they achieve PR followed by maintenance therapy. Pts not eligible for transplant are continued on effective therapy for up to 3 years as tolerated. Supportive care with bisphosphonates, vaccinations, zoster prophylaxis, and thromboembolism prophylaxis are outlined in this carepath. Results: From October 2012 to March 2015 carepath therapy was used in 53 pts not eligible for or unwilling to participate in clinical trials. Outcome data was attained through July 31, 2015 and median follow up was 16 months. 10 pts are off carepath treatment due to death (n=4), drug induced anorexia (n=1), or disease progression (n=5). 5 of these 10 pts were treated with ≥ 3 drugs. 3 of the 4 deaths occurred in pts high risk by FISH or MyPRS analysis. For all pts, response rates of VGPR or better were 55% in pts treated with 2 drugs and 41% in pts treated with ≥ 3 drugs. Of the 43 pts remaining on carepath based therapy, 26 pts have required only 2 drugs during the induction phase of treatment with 58% achieving at least very good partial response (VGPR) prior to either transplant or consolidation maintenance therapy. 17 pts required 3 or more drugs during the induction phase with 35% achieving at least VGPR prior to transplant or consolidation maintenance. Grade 3 or higher toxicity included hyperglycemia (n=4) due to dex, neutropenia (n=4) due to len, febrile neutropenia (n=2) due to len, insomnia (n=2) due to dex, and upper respiratory infection (n=2). One episode each of acute coronary syndrome due to dex (pt not on len), pancreatitis due to dex, anorexia due to len, sensory peripheral neuropathy due to bort, and tumor lysis syndrome due to len/dex occurred. Conclusion: Response adapted carepath based therapy provides effective disease control for the majority of MM pts treated while limiting cost due to the lower utilization of 3 drug therapy. While overall survival data is immature, the primary goal of response adapted therapy is to improve overall survival of MM pts by limiting early development of multi-drug resistant subclones. 55% of our pts required only 2 drug induction therapy to achieve a VGPR or better and 84% of these patients remain on carepath based therapy. Estimated cost savings on drug alone is over $4000 per cycle in the 2 drug treated pts. Cost savings may be underestimated as 73% of pts received len/dex as induction therapy and thus incurring less infusion related cost. Disclosures Valent: Takeda/Millennium: Speakers Bureau; Celgene: Speakers Bureau. Off Label Use: cyclophosphamide for the treatment of multiple myeloma. Faiman:Amgen/Onyx: Consultancy; Celgene: Consultancy, Speakers Bureau; Takeda/Millennium: Consultancy. Hamilton:Takeda/Millennium: Speakers Bureau. Smith:celegene, spectrum, genentech: Honoraria. Reu:Takeda/Millennium: Research Funding; Novartis: Research Funding; Celgene: Research Funding.

Description: Background: Overall response rate and response duration in newly diagnosed multiple myeloma (ndMM) has increased in the last decade. However, majority of patients eventually progress and receive multiple lines of therapy. Progression in MM is defined by rise in monoclonal protein and/or clinical manifestations of end-organ damage. However, there is a lack of evidence on the prognostic implication of pattern of progression in the current era. We have hypothesized that patients with clinical manifestations of end-organ damage at first progression have an inferior post-progression overall survival (OS) compared to those with biochemical progression alone. Method: We evaluated all ndMM patients between 1/1/2008 and 12/31/2015 at the Cleveland Clinic. Key inclusion criterion was patients experiencing first progression requiring an additional line of therapy. Patients with primary refractory disease and those in continued 1st remission at latest follow-up were excluded. Progression was categorized into 2 groups: Biochemical Progression (BP) and Clinical Progression (CP; implying CRAB features). Patients with CP were further stratified based on the presence of extramedullary disease (EM): CP+EM and CP-EM. Progression-free survival (PFS) and OS from first progression were estimated with Kaplan-Meier curves and compared among groups with log-rank test. Cox analysis was used to identify prognostic factors for OS and PFS. Potential prognostic factors included progression pattern, age, gender, race, ISS stage at diagnosis, FISH cytogenetics at diagnosis, metaphase cytogenetics at diagnosis, time from diagnosis to first progression, best response at first remission, frontline autologous stem cell transplant (ASCT), and whether progression occurred while on therapy. Results: A total of 527 patients with ndMM were evaluated, among which, 257 experiencing 1st progression were included in our analysis. The median age at progression was 64 years. The median time from diagnosis to first progression was 23 months. An autologous stem cell transplantation (ASCT) after induction therapy in 1st remission was performed in 26% of patients. At 1st progression, BP alone was noted in 52% (n=134), CP -EM in 34% (n=87) and CP+EM in 14% (n=36) of patients. In the CP-EM group, the most common mode of progression was development of new bone lesions (76%) followed by anemia (33%), renal insufficiency (18%) and hypercalcemia (13%), with ≥1 mode in approximately one-third of patients. In the CP+EM group, the most common mode of EM progression was development of new plasmacytomas (89%), followed by emergence of circulating plasma cells (14%), with 1 patient having both. A total of 84% of patients progressed on anti-myeloma therapy, which reflects the contemporary practice of continuous therapy in MM. After first progression, 68% received proteasome inhibitors (PIs), 64% received immunomodulatory drugs (IMiDs) and 11% received monoclonal antibodies (MoAbs). Salvage ASCT in 2nd remission was performed in 12% of patients. A total of 105 patients (41%) were alive at latest follow-up, with the median follow-up of survivors being 26 months from 1st progression. Median time from diagnosis to 1st progression was shorter in the CP+EM (12 months) compared to CP-EM (25 months) and BP (24 months) groups (P

Description: INTRODUCTION: Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplant (HCT) resulting in significant morbidity and mortality. The combination of tacrolimus and sirolimus (TAC/SIR) has emerged as a GVHD prophylaxis platform preferred by many institutions given its association with rapid engraftment and acceptable transplant-related toxicity. However, overlapping toxicities between the two drugs can lead to intolerance and premature discontinuation in some patients. There is limited literature describing outcomes and subsequent management of such patients. The goal of this study is to investigate the clinical outcomes of patients becoming intolerant to the combination of TAC/SIR prophylaxis. METHODS: We retrospectively evaluated consecutive adult patients (n=100) at the Moffitt Cancer Center who received allogeneic HCT with TAC/SIR for GVHD prophylaxis in 2018. TAC/SIR intolerance was defined as discontinuation due to the toxicity of either TAC or SIR before post-transplant day 100. Survival analyses were estimated from the time of transplant with the Kaplan-Meier method and compared using the log-rank test. Patients intolerant of this prophylaxis regimen were compared to patients who completed 〉100 days of therapy, using Mann-Whitney U test for continuous variables and Pearson Chi-square tests for categorical variables. All statistical analyses were performed using SPSS v25 and NCSS v11. RESULTS: Demographics and clinical characteristics of all patients are summarized in Table 1A. TAC/SIR intolerance occurred in 25% (24 discontinued TAC, 1 discontinued SIR) of patients at a median duration of therapy of 19 days (range 4-92). The most common TAC/SIR toxicity (Table 1B) was acute kidney injury (AKI, n=11, 44%), followed by thrombotic microangiopathy (TMA, n=3, 12%). Baseline metabolic and clinical variables including creatinine, liver function, and conditioning intensity were not predictive of TAC-SIR intolerance. At a median follow-up of 10 months, the median overall survival (OS) for patients intolerant of TAC/SIR was 10 months versus was not reached for the patients without intolerance (HR 5.42; 95% CI 1.71-17.14; p

Description: Background: CD19-directed chimeric antigen receptor (CAR) T cell therapy is FDA approved for relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) and variants. Due to active lymphoma, "bridging" therapy may be needed to maintain disease control during the 3 or more weeks required for autologous CAR T manufacturing. Bridging therapy was not allowed in trials of axicabtagene ciloleucel (axi-cel), but could improve outcomes by reducing tumor burden. Bridging chemotherapy is one option, however toxicity and chemo-refractory disease are potential concerns. Here we report a case series of patients receiving bridging radiation therapy (XRT) prior to axi-cel therapy, of which the majority had double hit lymphoma. Patient Characteristics: As of July 31, 2018 eight patients received XRT as part of their bridging therapies. Overall, patients had a median of 3 prior lines of chemotherapy (range 2 to 5). Two were primary refractory to their first two lines of chemotherapy. Six of the 8 patients had double hit lymphoma by FISH. All patients received 3-4 Gy per fraction to a total median dose of 20 Gray (range 9 - 30 Gy). The most commonly used regimen was 30 Gy in 10 fractions (3/7 patients). Four patients received bridging chemotherapy in addition to XRT, mainly oral cytoxan. In 2 patients the XRT was given up until the day of leukapheresis and in 1 of these patients it was continued after leukapheresis. In 6 additional patients the XRT started after leukapheresis. Overall, XRT was completed at a median of 9 days (range 3 - 22 days) prior to starting Flu/Cy conditioning. The median mass diameter receiving XRT was 13.6 cm (range 3 - 30 cm). Outcomes: No significant adverse events were noted at the local site of XRT before or after CAR T infusion. Response assessment within the field of radiation is complicated by a short duration between end of XRT and restaging prior to Flu/Cy conditioning. Nonetheless, only one patient experienced progressive disease in-field after XRT and most had stable disease in-field. Of the 4 cases where the baseline LDH was elevated, only the patient with PD saw their LDH rise after the completion of XRT, while the other 3 of 4 patients had declining LDH at the time of Flu/Cy conditioning. In 7 patients evaluable for toxicity, there was one case of severe cytokine release syndrome (CRS). This event occurred in the patient who progressed through XRT and had rising LDH and declining performance status prior to CAR T infusion (this patient later died of infection). In the other 6 patients the maximum CRS was grade 1 or 2. Three out of the 7 patients had grade 3 or 4 CAR T related encephalopathy syndrome (CRES). For lymphoma outcomes at day 30, 1 patient was in CR, 2 patients PR, 2 patients with SD and 1 patient with PD (Lugano criteria). Two patients are evaluable at day 90 with PR, although one of these patients subsequently relapsed at month 4 (in-field to the prior radiation). Conclusions: Bridging XRT (with or without chemotherapy) can be safely administered and provides disease control in refractory poor risk DLBCL patients prior to axi-cel therapy. All patients were able to receive axi-cel. CAR T-related toxicity occurred, but in this case series was most likely related to disease aggressiveness (6 of 8 patients were double hit) and tumor burden. Further research should focus on the immunologic effects of XRT and its impact on CAR T cell efficacy and toxicity. Table. Table. Disclosures Chavez: Humanigen: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Speakers Bureau; Merck: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Davila:Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees. Locke:Cellular BioMedicine Group Inc.: Consultancy; Kite Pharma: Other: Scientific Advisor; Novartis Pharmaceuticals: Other: Scientific Advisor.