ALBERT

Description: Background: Recent approval of ruxolitinib (rux) for steroid refractory graft versus host disease (GvHD) has revolutionized the field and provided tremendous choice for the patients. However, the side effects including thrombocytopenia leads to dug discontinuation and intolerance. We have previously shown that adoptive therapy with cord blood (CB) derived T regulatory (Treg) cells can prevent and treat GvHD. We hypothesized that the addition of CB Treg therapy to rux based therapy can augment overall efficacy. Methods: CellTrace Violet suppression assay was performed to evaluate the suppressor function of CB Treg cells in the presence or absence of rux. Xenogenic GvHD mouse model was utilized where the NSG mice underwent sublethal irradiation on day -1 followed by injection of 1x107 donor peripheral blood (PB) mononuclear cells (MNCs) on day 0. Oral rux at 1 mg daily was fed continuously to the mice in the presence or absence of 1x107 CB Treg cells, tagged with CellTrace Violet dye, administered on days +4, +7, +11, +18. Mice were followed every other day for weight, GvHD score and survival. Serial blood draws were performed to analyze for cell compartment and cytokine assays. Results: We examine whether the addition of rux impacts the suppressor function of CB Treg cells. Varying concentration of rux including 0.01, 0.05, 0.1 and 0.5 µM were added at 24, 48 and 96 hours of the cell suppression assay. The addition of rux 0.05 µM at 48 hours of the cell suppression culture led to a restoration of poor cell function (Figure A). Lowest GVHD score was reported in the rux+CB Treg combination arms at day +14 when compared to rux alone or CB Treg alone arm which (Figure B) translated into a superior survival in the rux +CB Treg arm (Figure C). Furthermore, an increase in the hemoglobin level (Figure D) and the platelet count (Figure E) was demonstrated in the rux+CB Treg arm. Addition of rux led to longer persistence of the injected CB Treg cells on day 14 (data not shown) which correlated with the increase in the plasma level of the pro-Treg cell signaling markers including IL-7 (Figure F) and IL-15 (Figure G). A decrease in the IL-4 production supported the increased Treg cell function (Figure H). A synergistic suppression of inflammatory cytokines including IL-17 (Figure I) and IL1A (Figure J) was evident in the rux+CB Treg arm. Conclusion: The combination of CB Tregs with ruxolitinib leads to improved overall survival, decreased inflammatory cytokines and improved hematologic parameters. Such combination should be explored in a clinical setting Figure Disclosures Sadeghi: Cellenkos Inc.: Current Employment. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Description: Background. Systemic lupus erythematosus (SLE) is associated with widespread inflammation with multi-organ involvement where renal failure is the most dreaded and fatal complication. Adoptive therapy with cord blood (CB) derived T regulatory cells has been shown to improve outcomes in disease driven by inflammation including graft versus host disease (GvHD), inflammatory bone marrow disorder, COVID-19 induced acute respiratory distress syndrome. We hypothesize that CB Treg therapy can treat lupus nephritis. Methods. The suppressive abilities of CB Tregs expressing CD4+CD25highCD127lowFoxP3+ were assayed by human cytokines assay kits (IL-10, IFN-γ, IP-10, TNF-α, IL-6, and IL-17A) in the cell culture supernatants. For examining the efficacy of CB Tregs in vivo, SLE xenograft model was created with female Rag2-/-γc-/- mice transplanted with 3x106 human SLE-peripheral blood mononuclear cells (PBMCs) by intravenous injection on day 0. The mice were allowed to develop disease and on day 30 post-transplant, they were divided into 2 groups: i) control and ii) treatment. 1x107 ex vivo-expanded, cryopreserved, allogeneic, non-HLA matchedCB Tregs were injected into SLE xenografts intravenously once per week for 4 weeks through the tail vein. Serial blood draws were performed for the phenotypic analysis, cytokine assay and anti-double stranded (ds)DNA IgG antibody analysis. Serial examination of the urine samples was performed for creatinine and albumin quantification. Histopathologic examination of the harvested organs was performed at the time of planned euthanasia at 13 weeks. Results. Co-culture of CB Tregs with the pathogenic SLE-PBMCs decreased the secretion of inflammatory cytokines including IFN-γ, IP-10, TNF-α, IL-6, and IL-17A (Figure A) with a reciprocal increase in the secretion of the anti-inflammatory IL-10 cytokine (Figure B). Adoptive therapy with CB Treg cells led to a significant decrease in circulating CD8+ effector T cells and an increase in CD4+ helper T cells (Figure C). CB Treg recipients showed preserved weight gain (Figure D), lower GvHD score (Figure E) and improved overall survival (Figure F). A significant decrease in proteinuria at 9 weeks post-transplant (Figure G) correlated with a decrease in anti-dsDNA IgG Ab levels (Figure H) and soluble CD40 ligand levels (Figure I). Histopathological results from two index cases from each arm (Figure J) demonstrated that CB Treg recipients show reduced T-cells (CD3+) (Figure K) and B-cells (CD20+) (Figure L) in the kidneys, as well as a decrease in the lymphoid infiltration into glomeruli and renal parenchyma as compared to the control arm (Figure M). Conclusion. We are the first to demonstrate the benefit of allogeneic CB Treg cell therapy for treatment of lupus nephritis. We propose to examine such a strategy in the clinical setting. Figure Disclosures Nishimoto: Janssen Pharmaceutical K.K.:: Research Funding; Bayer Yakuhin, Ltd:: Research Funding. Sadeghi:Cellenkos Inc.: Current Employment. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Description: Disease relapse remains the major cause of treatment failure following hematopoietic transplantation for AML/MDS. A major goal is to develop more effective antileukemic regimens without excessive toxicity. Fludarabine (Flu) with IV Busulfan (Bu) recently has replaced TBI- and double alkylator regimens in pretransplant conditioning because of its improved safety. Post-transplant relapse is still a major concern. Clofarabine (Clo) has improved antileukemic activity compared with Flu, and cell line studies indicated that Flu and Clo with Bu may be synergistic and superior to Flu alone with Bu. We previously conducted a phase II study of different combinations of Flu and Clo with Bu; the best results were obtained with Flu 10 mg/m2 and Clo 30 mg/m2 daily, with Bu, in four daily doses. We then performed a phase III randomized controlled trial comparing Flu-Clo-Bu (FCB) with our standard Flu-Bu regimen. Busulfan was given with PK-guided dosing to an average daily AUC of 6000 mM-min for age ≤60 and 4000 mM-min for patient ages 61-70. GVHD prophylaxis was tacrolimus-mini methotrexate. Unrelated donor recipients received low-dose rabbit ATG, total dose of 4 mg/kg. Patients aged 3-70 with intermediate or high risk AML or MDS, with PS〉70% and adequate organ function were eligible if they had an HLA identical related or 9/10 or 10/10 matched unrelated donor. There was no restriction for preexisting comorbid conditions. Patients were stratified based on disease status, complete remission (CR) vs. no CR (NCR). 250 patients were randomized; 120 received FCB and 130 got Flu-Bu. 95 had a matched sibling, 155 a matched unrelated donor. Median age was 51 yrs. 181 had AML, 69 MDS, and 92 (37%) had poor risk cytogenetics. 133 patients were in remission; 117 had active disease. Comorbidity indices (HCT-CI) varied from 0-10 and were evenly distributed between the groups. Performance status was 〉90% in 88%. All evaluable patients (n=249) achieved engraftment. 95 (38%) developed grade 2 and 16 (6%) grade 3-4 acute GVHD, while 93 (39%) got chronic GVHD. The median progression-free survival (PFS) for the FCB group was 39.3 mos and for the Flu-Bu group was 28.1 mos. There was a significantly lower risk of progression with FCB (p=0.025), but this benefit was offset by a higher risk of NRM (p=0.018) (Fig. a). There was no significant difference in PFS for patients in CR, but [NCR age ≤60 years] patients had median PFS of 28 mos with FCB vs. 8 mos with Flu-Bu (Fig. b). For patients age 〉 60 years, FCB yielded a median PFS ~25 mos compared with 6 mos with Flu-Bu (Fig. c). Additional analysis revealed that NCR patients with a low HCT-CI (0-2) benefited more from FCB than from Flu-Bu. The overall survival (OS) for the (NCR, HCT 0-2) group was also longer with FCB than with Flu-Bu (Fig. d). A Bayesian regression analysis including treatment-covariate interactions showed that most of the benefit of FCB was seen in this subgroup, while patients with HCT scores of ≥3 were less likely to benefit overall from FCB due to higher TRM with FCB. Our trial demonstrates the safety of the FCB regimen in patients with HCT 0-2 and better disease control with FCB compared with Flu-Bu in NCR patients. Patients with ≥3 comorbid conditions are at increased risk for TRM associated with FCB, somewhat offsetting the antileukemic benefit. Thus, clinical application of FCB should take CR status and performance status into account, and also include a personalized assessment of the risk for treatment-related complications based on the nature and number of preexisting comorbid conditions. Finally, age did not play a role for the use of FCB; it can be safely utilized in appropriate patients up to 70 years of age, and can be expected to yield better disease control. Figure Disclosures Alousi: Therakos: Research Funding; Incyte: Honoraria, Research Funding; Alexion: Honoraria. Bashir:Amgen: Other: Advisory Board; Purdue: Other: Advisory Board; KITE: Other: Advisory Board; Takeda: Other: Advisory Board, Research Funding; Celgene: Research Funding; Acrotech: Research Funding; StemLine: Research Funding. Ciurea:Kiadis Pharma: Current equity holder in publicly-traded company, Research Funding. Hosing:NKARTA Inc.: Consultancy. Kebriaei:Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Amgen: Other: Research Support; Kite: Other: Served on advisory board; Jazz: Consultancy. Oran:Celgene: Consultancy; ASTEX: Research Funding; Arog Pharmaceuticals: Research Funding. Rezvani:Pharmacyclics: Other: Educational grant; Formula Pharma: Membership on an entity's Board of Directors or advisory committees; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; GemoAb: Membership on an entity's Board of Directors or advisory committees; Virogen: Membership on an entity's Board of Directors or advisory committees; Affimed: Other: Educational grant; Takeda: Other: Licensing agreement. Shah:BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Shpall:Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Popat:Bayer: Research Funding; Novartis: Research Funding. Nieto:Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Champlin:Omeros: Consultancy; Takeda: Patents & Royalties; Actinium: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy. OffLabel Disclosure: The use of fludarabine and clofarabine is not approved by the FDA in pretranpslant conditioning therapy.

Description: Introduction Classic Hodgkin's lymphoma (cHL) is a highly curable lymphoid malignancy. Most of the patients receive either bleomycin or brentuximab vedotin (BV) based therapies as a frontline treatment. Treatment alterations are common and can be related to toxicity, patient's preference, and/or clinical evidence of response. The aim of our study is to explore the frequency and characteristics of treatment alterations, especially bleomycin and BV, in frontline therapies used in newly diagnosed cHL. Methods This single center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Patients' charts were reviewed to assess frequency of treatment discontinuation at the time of frontline therapy and underlying reasons for any treatment alterations. The primary aims were to assess the frequency of treatment alterations and its effects on overall survival (OS), and progression-free survival (PFS). Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and lab measurements, and frequency counts and percentages for categorical variables such as race, gender, and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results In the studied period, 644 patients met the inclusion criteria. The median age at diagnosis was 33 years (range:9-85) with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients. Ninety-seven percent of patients had 0-1 Eastern Cooperative Oncology Group (ECOG) performance status. Histological subtype was predominately nodular sclerosis (83%). International prognostic index at the time of diagnosis was ≥4 in 13% of patients. Most of the patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%). Other therapies included brentuximab vedotin (BV)(13%) and checkpoint inhibitors (CPIs) (6%, as a part of clinical trial). Patient's demographics are outlined in Table.1. Treatment alteration, which included either addition or omission of drug/s, occurred in 26% of patients. The most common discontinued drugs were bleomycin (79%), and BV (15%). Of the patients who were started on ABVD based therapy, the frequency of bleomycin discontinuation was 26% (116 of 455 patients). The most common reasons for bleomycin discontinuation were: treatment response as per the RATHL study (49%), pulmonary toxicity (27%) and other treatment-related toxicity (9%). Of the patients who were started on frontline BV based therapy, the frequency of BV discontinuation was 26% (20 of 78 patients). The most common reasons for BV discontinuation were: peripheral neuropathy (65%), skin rash (10%) and other treatment-related toxicity (25%). Patients who discontinued bleomycin due to adverse events (AEs) had a higher chance of primary refractory disease at the end of frontline treatment (19% vs. 15%, p-value: 0.005) while patients who discontinued bleomycin due to treatment response had similar rates of primary refractory disease (13% vs. 15%, p-value: 0.57). The median cycles number of bleomycin based therapy were the same (6 cycles) among all the groups (those who continued bleomycin without AEs or discontinuation, patients who discontinued bleomycin for treatment response and patients who discontinued bleomycin for AEs) . Patients who discontinued BV due to AEs had similar outcome to the patients who continued the treatment without alterations. Conclusions Frontline treatment alterations in cHL are common. Positron emission tomography treatment response based bleomycin discontinuation was not associated with worse PFS or OS. However bleomycin discontinuation secondary to AEs was associated with a statistically significant higher rate of primary refractory disease and subsequent worse PFS and OS. BV discontinuation secondary to AEs didn't result in worse outcomes. Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Iyer:CRISPR:Research Funding;Spectrum:Research Funding;Merck:Research Funding;Afffimed:Research Funding;Rhizen:Research Funding;Seattle Genetics, Inc.:Research Funding;Legend Biotech:Consultancy;Daiichi Sankyo:Consultancy;Trillium:Research Funding;Curio Biosciences:Honoraria;Target Oncology:Honoraria.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Secura Bio:Other: Grant Support;Astra Zeneca:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Pulse Biosciences:Consultancy;Molecular Templates:Research Funding;BioInvent:Research Funding;VelosBio:Research Funding;Beijing Medical Award Foundation:Honoraria;Juno:Consultancy, Research Funding;Oncternal:Consultancy, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;InnoCare:Consultancy;Loxo Oncology:Consultancy, Research Funding;Verastem:Research Funding;Acerta Pharma:Research Funding;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;OncLive:Honoraria;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Nobel Insights:Consultancy;Guidepoint Global:Consultancy;Dava Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Targeted Oncology:Honoraria.Lee:Celgene:Research Funding;Guidepoint Blogal:Consultancy;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau;Oncternal Therapeutics:Research Funding;Seattle Genetics:Research Funding;Takeda:Research Funding.

Description: Introduction Vitamin D deficiency is a modifiable risk factor for multiple malignancies. There is growing evidence that associates vitamin D deficiency with progression-free survival (PFS) and overall survival (OS) in patients with classic Hodgkin lymphoma (cHL). Supplemental ergocalciferol/cholecalciferol may improve chemosensitivity of malignant cells to chemotherapy as evidenced by reduction in the rate of tumor growth in a cHL- xenograft animal model. The goal of our study is to explore the association of pretreatment vitamin D levels on survival outcomes of patients with cHL. Methods We retrospectively reviewed the records of patients who were first seen at The University of Texas MD Anderson Cancer Center between January, 2016 and May, 2020 for newly diagnosed cHL. Patient charts were reviewed to assess demographic information, clinical staging at the time of vitamin D assessment, pretreatment 25-hydroxyvitamin D (25(OH) D) level and vitamin D supplementation. Vitamin D deficiency was defined as a 25(OH)D level 〈 30 nmol/L. PFS and OS outcomes were evaluated for these patients. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, and 25(OH) D level, and frequency counts and percentages for categorical variables such as race, gender, vitamin D supplementation and response were analyzed. The Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results 644 patients met the inclusion criteria of which 483 patients had their vitamin D levels assessed at the time of initial visit to this center. The median patient age at diagnosis was 33 years with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients of which the International Prognostic Score was ≥4 in 13% of patients. Patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%) and other agentss (6%). Patient demographics are outlined in Table.1. Pretreatment 25(OH)D level was assessed in 75% of the patients. The median 25(OH)D level was 25 nmol/L (range: 2-78 nmol/L). Vitamin D deficiency was present in 320 of 483 (66%) patients. Ergocalciferol/cholecalciferol supplementation was used in 29% of patients. There was no statistically significant association of vitamin D deficiency with advanced stage (p-value: 0.64). PFS rate at 10 years was significantly longer in patients with normal 25(OH)D level (40% vs 27%, p-value: 0.0481). Ergocalciferol/cholecalciferol supplementation was associated with a 6% improvement of PFS, however this difference was not statistically significant. No OS difference was noted between vitamin D deficient and non-deficient patients, an observation that persisted in patients on vitamin D supplementation versus not on supplementation. Conclusions Vitamin D deficiency was associated with inferior PFS with a 13% difference in vitamin D deficient versus non-deficient patients. There was a numerical PFS benefit associated with ergocalciferol/cholecalciferol supplementation. An OS benefit was not observed as the duration of follow up may not have been sufficient to observe the differential impact of vitamin D levels. Vitamin D screening and replacement is done in patients with newly diagnosed cHL and should be encouraged given the potential benefit from such approach. Prospective studies are warranted to establish the relationship between vitamin D level, supplementation and outcomes in cHL patients. Figure Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Nieto:Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support;Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Lu Daopei Medical Group:Honoraria;Beijing Medical Award Foundation:Honoraria;OncLive:Honoraria;Molecular Templates:Research Funding;Verastem:Research Funding;Dava Oncology:Honoraria;Guidepoint Global:Consultancy;Nobel Insights:Consultancy;Oncternal:Consultancy, Research Funding;InnoCare:Consultancy;Acerta Pharma:Research Funding;VelosBio:Research Funding;BioInvent:Research Funding;Juno:Consultancy, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;Loxo Oncology:Consultancy, Research Funding;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;MoreHealth:Consultancy;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding.Lee:Takeda:Research Funding;Seattle Genetics:Research Funding;Oncternal Therapeutics:Research Funding;Guidepoint Blogal:Consultancy;Celgene:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau.

Description: Introduction. The efficacy of CAR T-cell therapy in relapsed/refractory (r/r) LBCL has been associated with peak CAR T-cell expansion post-infusion. One of the critical factors that drives CAR T-cell expansion is the availability of homeostatic cytokines, such as IL-15, at the time of infusion. Consistent with this hypothesis, serum IL-15 levels have been associated with CAR T-cell therapy expansion and efficacy, higher levels favoring improved outcomes. Since induction of lymphodepleting conditioning (LDC) therapy results in decreased consumption of homeostatic cytokines and thereby increases their serum levels, we aimed to determine whether the magnitude of change in absolute lymphocyte count (ALC) pre- and post-conditioning, referred to as delta lymphocyte index (DLIx), impacts outcomes after CAR T-cell therapy in r/r LBCL. Methods. This is a retrospective study of all patients with r/r LBCL treated with standard of care (SOC) axicabtagene ciloleucel (axi-cel) at MD Anderson Cancer Center between 01/2018 and 04/2020 (data cut-off 06/30/2020). DLIx was defined as the difference in ALC between day of initiation of LDC and day of axi-cel infusion. All patients received LDC therapy with cyclophosphamide and fludarabine. CRS and ICANS were prospectively graded according to CARTOX criteria from 01/2018 to 04/2019, and ASTCT criteria from 05/2019 onward. Response to treatment and progression were defined according to 2014 Lugano criteria. Results. All 171 LBCL patients treated with SOC axi-cel were included in the analysis. At time of initiation of LDC, median age was 59 years (range, 18-85 years), 120 (70%) were male, 151 (88%) had an ECOG performance status of 0-1; 96 (56%) had an IPI 〉 3, median number of prior systemic therapies was 4 (range, 2-15), 45 (26%) had received an autologous SCT, 3 (2%) an allogeneic SCT; 86 (50%) patients received bridging therapy, including chemotherapy in 52 (30%), radiotherapy in 21 (12%), and biological therapy or corticosteroids in 13 (8%). Median ALC at time of LDC was 0.6 X 109/L (range, 0-2.8 X 109/L) and 〈 lower limit of normal (LLN) in 131 (77%) patient; at time of axi-cel infusion it was 0.03 X109/L (range, 0-1.9 X109/L), and median DLIx was 0.5 X 109/L (range, 0.01-2.75 X 109/L). Ten (6%) patients experienced a delay between LDC and axi-cel infusion, with a median time of 13 days (range, 7-19 days), but no association between delay and DLIx was observed (p=0.79). On univariate analysis, the baseline characteristics associated with low DLIx were ALC 〈 LLN (p

Description: Background. Inflammatory tumor microenvironment leads to T cell exhaustion in multiple myeloma leading to treatment failure and relapse. Specifically, T cell based therapies including bispecific antibodies and chimeric antigen receptor (CAR) T cell are associated with the additional side effects of non-specific T cell activation and cytokine release syndrome. Adoptive therapy with allogeneic cord blood (CB) T regulatory (Treg) cell therapy has been shown to be safe with clinical efficacy in a wide range of diseases including graft vs. host disease (GvHD), inflammatory bone marrow failures and COVID-19 induced acute respiratory distress syndrome. Furthermore, combination of Tregs with donor lymphocyte infusion (DLI) has led to resolution of leukemia relapse without GvHD flare up. We hypothesize that co-administration of Tregs with adoptive T cell based therapy will improve myeloma outcomes. Methods. 3x106 GFP-labeled MM.1S cells were injected into NSG mice followed by 5x106 CD3+ T conventional (Tcon) cells on day 14. In a subset of the Tcon treated mice, 1x107 CB Treg cells were injected on day 47, 54 and 61. Mice were followed every other day for weight and GvHD score. Non-invasive bioluminescent imaging (BLI) was performed serially. Weekly blood draw was performed for cell analysis and cytokine assays. At the time of euthanasia, blood, spleen and bone marrow were harvested for histopathology and flow analysis. In a subsequent experiment, intra-peritoneal injection of the bi-specific antibody against CD3 and BCMA (BCMA-BiTE) was administered in the xenogenic myeloma model in the presence or absence of CB Treg cells. Pan T cells were injected into all mice to facilitate the anti-tumor action of BiTE. Results. Both Tcon and Tcon+Treg recipients maintained their body weight compared to myeloma alone or myeloma + Treg arm (Figure A). All mice showed evidence of tumor growth by day 20 (Figure A). Widespread MM.1S cell growth in the myeloma only mice at day 27 was demonstrated by BLI whereas no measurable tumor growth was evident in Tcon recipients or Tcon+Treg recipients. By day 69, Tcon only mice were significantly increased tumor growth compared to Tcon+Treg recipients (Figure B). While circulating multiple myeloma cells were detected in myeloma alone and myeloma+Treg arm, no such evidence was detectable in the Tcon or Tcon+Treg recipients. However, upon euthanasia, extramedullary relapse of myeloma as retroperitoneal mass was detected in Tcon recipient (Figure C). Addition of Treg + BiTE led to a similar degree of tumor control compared to BiTE alone treated mice, however, a significant weight loss was observed in this arm (Figure D) with a corresponding high GvHD score (Figure E). Furthermore, addition of CB Treg cells led to decrease of T cell exhaustion phenotypic markers (data not shown). Conclusion. We are the first to show that CB Treg cells can be administered in combination with the T-cell based immunotherapies directed against myeloma. Such a strategy should be examined in the clinical setting. Figure Disclosures Nishimoto: Bayer Yakuhin, Ltd:: Research Funding; Janssen Pharmaceutical K.K.:: Research Funding. Sadeghi:Cellenkos Inc.: Current Employment. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Patel:Nektar: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding; Precision Biosciences: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Description: Background: Compared to other peripheral T cell lymphomas (PTCLs), patients with AITL have an aggressive clinical course and poor outcomes with conventional chemotherapies. Previous studies reported overall survival (OS) of

Description: Introduction The pathogenesis of classic Hodgkin's lymphoma (cHL) is largely unsettled. Previous studies have provided limited support to the possible association between tobacco smoking and outcome in cHL with inadequate evidence of a dose-outcome relationship. Smoking can result in a multitude of preventable malignancies, thus we studied the association between smoking, the initial stage of cHL and survival outcomes. Methods This single-center study included patients with a diagnosis of cHL who were first seen at The University of Texas MD Anderson Cancer Center between January 1,2016 and May 28, 2020 for either newly diagnosed cHL or relapsed/refractory (R/R) cHL. Patients' charts were reviewed to assess the history of active smoking, former smoking and the amount of smoking (measured as pack-year). Former smoking was defined as history of smoking prior to the diagnosis of cHL and no active smoking at the time of diagnosis. The primary aims were to assess overall survival (OS), progression-free survival (PFS) and frequency of advanced disease at the time of diagnosis. Descriptive statistics including mean, standard deviation, median, and range for continuous variables such as age, amount of smoking and lab measurements, and frequency counts and percentages for categorical variables such as race, gender, history of current/prior smoking and response were analyzed. Kaplan-Meier method was used for time-to-event analysis including PFS and OS. Median time to event in months with 95% confidence interval (CI) was calculated. The Log-rank test was used to evaluate the difference in time-to-event endpoints between patient groups. Statistical software SAS 9.4 (SAS, Cary, NC) and S-Plus 8.2 (TIBCO Software Inc., Palo Alto, CA) were used for statistical analyses. Results Between 2016 and 2020, 644 patients met the inclusion criteria. The median age at diagnosis was 33 years (range: 9-85 years) with 52% males. Advanced stage (stages III and IV) occurred in 45% of patients. Ninety-seven percent of patients had 0-1 Eastern Cooperative Oncology Group (ECOG) performance status. Histological subtype was predominately nodular sclerosis (83%). International Prognostic Index was =〉4 in 13% of patients. Most of the patients received doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) based therapy (77%), brentuximab vedotin (BV) based therapy (13%)and checkpoint inhibitors (CPIs) based therapy (6%). Patient's demographics are outlined in Table.1. The percentage of active smoking was low at 6% (median age of active smokers: 33.5). History of prior smoking occurred in 21% of patients. The mean amount of smoking was 1.87 pack-year (rang :0. 05-54 pack-year). Active smoking was associated with advanced stage (9.5% vs. 4.9%, p-value: 0.033). PFS rate at 5 years was similar in smokers and non smokers (52% vs. 54%, p-value 0.9). OS rate at 10 years was better in never smokers when compared to former smokers (95% vs. 77%, p-value: 0.017). Univariable Cox proportional hazards model for OS showed a significant association between amount of smoking and OS with hazard ratio of 1.04 (95% CI: 1.005 1.07, p-value: 0.025). Conclusions We report the largest analysis of smoking status and impact on advanced stage and cHL clinical outcomes. Smoking history is associated with inferior 10 year OS (18% lower OS in patients with history of former smoking). Active smoking was associated with advanced stage however the frequency of active smoking in our patient database was low at 6% compared to previous reports of higher incidence of up to 20%. Patients should be counseled against smoking to avoid worse outcome associated with smoking in many clinical conditions including cHL. Disclosures Parmar: Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.Iyer:Legend Biotech:Consultancy;CRISPR:Research Funding;Rhizen:Research Funding;Curio Biosciences:Honoraria;Target Oncology:Honoraria;Afffimed:Research Funding;Merck:Research Funding;Spectrum:Research Funding;Trillium:Research Funding;Daiichi Sankyo:Consultancy;Seattle Genetics, Inc.:Research Funding.Nieto:Astra Zeneca:Other: Grant Support;Secura Bio:Other: Grant Support;Affimed:Consultancy, Other: Grant Support;Novartis:Other: Grant Support.Chuang:Sage-Evidence=Based Medicine & Practice:Consultancy.Wang:Guidepoint Global:Consultancy;Dava Oncology:Honoraria;Loxo Oncology:Consultancy, Research Funding;Verastem:Research Funding;Beijing Medical Award Foundation:Honoraria;Targeted Oncology:Honoraria;OMI:Honoraria, Other: Travel, accommodation, expenses;AstraZeneca:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;OncLive:Honoraria;Molecular Templates:Research Funding;Celgene:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Kite Pharma:Consultancy, Other: Travel, accommodation, expenses, Research Funding;Pulse Biosciences:Consultancy;MoreHealth:Consultancy;Janssen:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Pharmacyclics:Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;BioInvent:Research Funding;Lu Daopei Medical Group:Honoraria;Juno:Consultancy, Research Funding;VelosBio:Research Funding;Acerta Pharma:Research Funding;InnoCare:Consultancy;Oncternal:Consultancy, Research Funding;Nobel Insights:Consultancy.Lee:Celgene:Research Funding;Seattle Genetics:Research Funding;Bristol-Myers Squibb:Consultancy, Research Funding;Aptitude Health:Speakers Bureau;Guidepoint Blogal:Consultancy;Takeda:Research Funding;Oncternal Therapeutics:Research Funding.

Description: Background.As a T cell driven process where release of inflammatory cytokines as a result of the proliferation and on target cell kill by chimeric antigen receptor (CAR)-T cells, cytokine release syndrome (CRS) can be potentially targeted by adoptive therapy with T regulatory (Treg) cells. Specifically, allogeneic cord blood (CB) derived Treg cells have now shown safety and efficacy in graft vs host disease (GVHD), we hypothesized that CB Treg cell therapy can be exploited for treatment of CRS. Method.Xenogenic lymphoma model was created using NSG mice where 0.3x106 GFP-labeled Raji cells were injected on day 0 in all mice followed by 0.3x106 cells of i) mock-CAR T, ii) no CART, ii) CD19-CAR T cells on day +5. Additional injections of 1x107 CB Treg cells on day +11, +18, +25 were added to the no CAR T arm and the CD19-CAR T arm such that there were 3 mice per arm. Mice were followed for weight, GVHD score and survival. Non-invasive bioluminescence was used to perform serial imaging to evaluate the tumor burden. Serial blood was drawn for cell analysis and cytokine assay. Result. As shown in figure A, in vivo proliferation of GFP-labeled Raji cells was evident in all mice day by day +4. CD19-CAR T but not the mock-CAR T cells decreased the tumor burden at day+11. However, at day +14 all mice including CD19-CAR T cell recipients showed progression whereas CD19-CAR T+CB Treg cell recipient showed no evidence of bioluminescence. A superior survival in the CD19-CAR T+CB Treg cells recipients was evident when compared to other treatment arms (Table A). At the time of euthanasia, different organs were evaluated for the detection of the CD19-CART cells and were recovered only in the CD19-CART+CB Treg cells recipients (Table B) . The CD19-CAR T recipients showed an increase in the inflammatory cytokines on day +16 PB samples including IFN-gamma (Figure B) and TNF-alpha (Figure C) which were decreased in the CD19-CAR T + CB Treg arm. Furthermore, a reciprocal increase of the anti-inflammatory cytokine IL-1RA was observed in the CD19-CAR T + CB Treg arm compared to the CD19-CAR T alone (Figure D). Conclusion. The addition of CB Treg cells to CD19-CAR T cells in a xenogenic lymphoma model led to dampening of the cytokine storm and improved on target efficacy of CAR T cells. This combination should be examined in clinical setting. Disclosures Sadeghi: Cellenkos Inc.:Current Employment.Nastoupil:Genentech, Inc.:Honoraria, Research Funding;Karus Therapeutics:Research Funding;Bayer:Honoraria;Gamida Cell:Honoraria;Gilead/KITE:Honoraria;Novartis:Honoraria, Research Funding;Merck:Research Funding;TG Therapeutics:Honoraria, Research Funding;LAM Therapeutics:Research Funding;Janssen:Honoraria, Research Funding;Pfizer:Honoraria, Research Funding;Celgene:Honoraria, Research Funding.Patel:Oncopeptides:Consultancy;Janssen:Consultancy, Research Funding;Precision Biosciences:Research Funding;Takeda:Consultancy, Research Funding;Nektar:Consultancy, Research Funding;Celgene:Consultancy, Research Funding;Bristol Myers Squibb:Consultancy, Research Funding;Poseida:Research Funding;Cellectis:Research Funding.Parmar:Cellenkos Inc.:Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.