ALBERT

Description: Background: IL-15-mediated responses have been shown to have a crucial role in the development, function, and survival of CD8+ T cells, natural killer (NK) cells, and NK T cells. However, exploiting native IL-15 is challenging due to its unfavorable pharmacokinetics and tolerability. NKTR-255 is a polymer-conjugated IL-15 that retains binding affinity to IL-15Ra, maintaining full spectrum of IL-15 biology. NKTR-255 also exhibits improved pharmacokinetics, thereby providing sustained pharmacodynamic responses without the need for daily dosing. Studies have indicated that NK cells from patients with multiple myeloma (MM) appear to be dysfunctional, and successful activity against MM cells requires highly active NK cells ideally activated from immunomodulatory agents or cytokine support. In recent years, several new agents have been introduced in the MM landscape to engage NK-mediated myeloma cell elimination, including the CD38-targeting monoclonal antibody daratumumab, and elotuzumab, further supporting the anti‐MM effect of NK cells in the post-autologous transplant setting. In non-Hodgkin lymphoma (NHL), studies have shown low peripheral blood NK cell counts are associated with poor clinical outcomes in diffuse large B-cell lymphoma patients receiving R-CHOP chemotherapy regimens. Recently published data indicate that NKTR-255 in combination with CAR T cells decreases tumor burden and increases survival compared to CAR T cells alone. NKTR-255 may address the need to boost NK cell quality and numbers in these patients with the purpose of aiding current approved therapies. Methods: In this phase 1, open-label, multi-center, dose escalation and dose expansion study of NKTR-255, patients with relapsed or refractory (r/r) MM or NHL with no available therapies will be eligible. In the dose escalation portion, approximately 46 patients will be enrolled. Successive cohorts of 3 patients each will receive single increasing doses of NKTR-255 until the maximum tolerated dose (MTD) is determined. All patients will receive NKTR-255 once every three weeks. Patients will be observed for a dose-limiting toxicity (DLT) window of three weeks following the first NKTR-255 dose. A two-parameter Bayesian logistic regression model (BLRM) will be used during the escalation part of the study for dose level selection and for determination of MTDs. The selected recommended phase 2 dose (RP2D) of NKTR-255 will be evaluated in two dose expansion cohorts. Cohort A will expand NKTR-255 in patients with r/r MM or NHL as a salvage regimen to further characterize safety and tolerability. Cohort B will combine NKTR-255 with daratumumab in patients with MM with progressive disease who have had at least 3 prior lines of therapy with no other regimens that would confer clinical benefit. Daratumumab will be administered IV at the standard approved regimen. The primary objectives of the study are to evaluate: safety, tolerability, MTD, and RP2D of NKTR-255 as a single agent, as well as safety and tolerability of NKTR-255 in combination with daratumumab in patients with r/r MM. Secondary objectives include measures biomarker and pharmacokinetic analyses. Figure Disclosures Shah: University of California, San Francisco: Employment; Nkarta: 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; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Poseida: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; Indapta Therapeutics: Equity Ownership. Turtle:Nektar Therapeutics: Other: Ad hoc advisory board member, Research Funding; T-CURX: Membership on an entity's Board of Directors or advisory committees; Allogene: Other: Ad hoc advisory board member; Humanigen: Other: Ad hoc advisory board member; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Patents & Royalties: Co-inventor with staff from Juno Therapeutics; pending, Research Funding; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Caribou Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Other: Ad hoc advisory board member; Novartis: Other: Ad hoc advisory board member. Cowan:Cellectar: Consultancy; Juno: Research Funding; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Abbvie: Research Funding. Chavez:Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Budde:F. Hoffmann-La Roche Ltd: Consultancy. Marcondes:Nektar Therapeutics: Employment, Equity Ownership. Lee:Nektar Therapeutics: Employment. Lin:Nektar Therapeutics: Employment, Equity Ownership. Zalevsky:Nektar Therapeutics: Employment, Equity Ownership. Tagliaferri:Nektar Therapeutics: Employment, Equity Ownership. Patel:Poseida Therapeutics, Cellectis, Abbvie: Research Funding; Oncopeptides, Nektar, Precision Biosciences, BMS: Consultancy; Takeda, Celgene, Janssen: Consultancy, Research Funding.

Description: Background EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO Classification. EBV+ DLBCL of the elderly is characterized by an aggressive clinical course and a poor outcome. Furthermore, it is unclear if patients with EBV+ DLBCL of the elderly benefit from the addition of rituximab to chemotherapy. The goal of this retrospective study is to evaluate the clinical relevance of rituximab in this entity in a cohort of Peruvian patients. Methods Between January 2002 and December 2012, all patients meeting criteria for EBV+ DLBCL were included in the analysis. Patients with evidence of immunosuppression were excluded. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or PAX-5 expression by immunohistochemistry. Clinical data were reviewed retrospectively and patients’ biopsies were evaluated for the immunohistochemical expression of BCL6, CD10, and MUM-1/IRF4. Overall survival (OS) was defined as the time between diagnosis and death or last follow-up. The Kaplan-Meiermethod was used to estimate OS curves, which were then comparedusing the log-rank test. P-values 1 in 60%, advanced stage (III/IV) in 58%, and elevated LDH levels in 44% of the patients. Based on the Hans classification, 81% had a non-germinal center profile. The median Ki67 expression was 80% (range 50-90%). The Oyama score distribution, which uses age 〉70 and presence of B symptoms, was 0 factors 14%, 1 factor 45% and 2 factors in 40% of the patients. Based on the International Prognostic Index (IPI) score, 0-2 factors were seen in 39% and 3-5 in 61% of the patients. Chemotherapy was not administered in 9 patients due to poor performance status. R-chemotherapy was administered in 17 patients (52%) and chemotherapy without rituximab in 16 patients (48%). The overall response rate (ORR) was 52%, with complete response (CR) in 42%, partial response (PR) in 9% and no response (NR) in 48%. The response rates in patients who received chemotherapy without rituximab were: CR 37.5%, PR 0%, and NR 62.5%. Response rates in patients who received R-chemotherapy were: CR 47%, PR 17%, and NR 35%. The odds ratio for a CR was 2.48 (95% CI 0.49-13.2; p=0.21) for patients receiving R-chemotherapy when compared with patients who received chemotherapy alone. The median OS for treated patients was 8 months with a 3-year OS of 40%. For patients receiving R-chemotherapy, the median OS was 20 months with a 3-year OS of 47% and for patients receiving chemotherapy without rituximab, the median OS was 5 months with a 3-year OS of 37.5% (log-rank p=0.12). The median OS in patients 60 and older was significantly superior with R-chemotherapy in comparison with chemotherapy alone (20 vs. 1.5 months, log-rank p=0.02) Conclusions Based on the results of our retrospective study, the addition of rituximab to chemotherapy show a statistical trend towards improved survival rates versus chemotherapy alone in our cohort of patients with EBV+ DLBCL. In a subset analysis, the addition of rituximab to chemotherapy showed a survival benefit in our cohort of EBV+ DLBCL patients 60 years of age and older . Disclosures: No relevant conflicts of interest to declare.

Description: Background: Outcomes to salvage therapy for patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) are suboptimal. Checkpoint blockade therapy (CBT) has been explored in the relapsed/refractory (R/R) NHL population, but response rates to single agent CBT therapy are modest. To date, there is no literature on whether treatment with CBT may sensitize NHL patients to subsequent therapy. We investigated the outcome of subsequent treatment in patients with R/R NHL who had received CBT in a large multicenter international retrospective analysis. Methods: Seventeen centers across the US and Canada are participating in this study to date. Medical records of each institution were queried to identify lymphoma patients who received CBT and were subsequently treated with an additional line of therapy. The primary aim of the current analysis was to determine the best response to post-CBT treatment in patients who discontinued CBT due to progression of disease (PD) or toxicity. Patients who discontinued CBT due to a complete response (CR), or patients whose best response to post-CBT therapy could not be determined due to death from another cause, were excluded from analysis. Responses were assessed using Lugano criteria. Survival status to date was analyzed for the entire study population and stratified by post-CBT treatment regimen categories and disease subgroups using the Kaplan-Meier method. Progression free survival (PFS) and overall survival (OS) were calculated for patients with at least stable disease (SD) to post-CBT treatment. Log rank tests were performed to test for statistical significance. Two-sided P

Description: Key Points A subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Description: Introduction REGN1979 is an anti-CD20 x anti-CD3 bispecific IgG4 antibody (Ab) modified to reduce Fc binding. Engaging both targets results in CD20-specific, local T-cell activation and cytotoxicity, a mechanism of action distinct from standard anti-CD20 Abs. We report updated promising efficacy results of a Phase 1 trial of REGN1979 in patients (pts) with relapsed/refactory (R/R) B-NHL previously treated with anti-CD20 Abs. Methods The primary objectives of the study are to determine safety, tolerability, and occurrence of dose limiting toxicities (DLTs). Other objectives include assessment of preliminary antitumor activity, pharmacokinetics (PK), and pharmacodynamics. Eligible pts with R/R NHL must have received at least 1 prior CD20-directed therapy. Treatment consists of 12 weekly doses of REGN1979 followed by every 2 week dosing for 12 doses for a total of 36 weeks. Guidelines are provided for management of cytokine release syndrome (CRS) and include steroids and/or tocilizumab at investigator discretion. Results As of June 1, 2018, 54 pts with B-NHL were treated with REGN1979 monotherapy: DLBCL (pt number [n]=30), FL (n=16), MCL (n=5), MZL (n=2), and WM (n=1). The median number of prior regimens was 3 (range, 1-11); 41 pts were refractory to their last prior systemic therapy, 18 had bulky disease, and 6 had prior HSCT. Pts were treated with REGN1979 0.03-27 mg and received a median of 7 (range, 1-24) doses. Eight pts remain on treatment, 13 completed treatment, and 33 discontinued therapy prior to the planned 36 wks (majority [n=22] due to progressive disease [PD]). There have been no DLTs to date. The most common treatment-related treatment-emergent adverse events (TR-TEAEs) included infusion-related reactions (IRR) or CRS; 26 pts experienced CRS (Grade 1-2, n=23; Grade 3, n=3) with a median duration of CRS of 2 (range 1-15) days. Six pts received tocilizumab. The severity of CRS symptoms declined through optimized pre-medication even with REGN1979 dose escalation. Other common Grade ≥3 TR-TEAEs were lymphocytopenia/ decreased lymphocyte count (n=8); neutropenia/ decreased neutrophil count (n=7); and thrombocytopenia/ decreased platelet count, hypotension, hypophosphatemia, and anemia (each n=3). Seventeen pts experienced a nervous system event including headache, dizziness, paraesthesia, dysgeusia, and peripheral neuropathy with no Grade ≥3 events; no neurologic event required termination of study drug. Seven pts died on study: PD (n=5), gastric perforation (n=1), and cardiac arrest (n=1). TEAEs leading to premature discontinuation of REGN1979 were Grade 3 fatigue (n=1), Grade 3 hemolysis (n=1), and Grade 2 pyrexia/Grade 2 tachycardia (n=1). Among 27 pts treated with REGN1979 ≥5 mg (dose associated with tumor killing in pre-clinical data), the overall response rate (ORR) was 55.6% (5 complete response [CR] and 10 partial response [PR]; Table/Figure). Responses were seen in 7/7 FL Grade 1-3a pts (5 CR, 2 PR), 6/15 DLBCL pts (all PR), 2/2 MCL pts (all PR). At 18 mg and 27 mg of REGN1979, 4 of 4 pts with DLBCL had best response of PR. Post data cut-off, 1 pt with a DLBCL best response of PR converted to CR. PK and pharmacodynamic assessments suggest that for pts treated with REGN1979 5-18 mg, best exposures in the first 3 weeks appear to linearly increase with dose. In pts treated with up to REGN1979 18 mg, a maximum mean Ctrough of 1.6 mcg/mL was observed in the first 3 weeks of weekly dosing. Studies of peripheral blood biomarkers demonstrated depletion of peripheral B lymphocytes, transient margination of circulating T-cells, and elevated circulating cytokines following REGN1979 dosing. Increased peak cytokine levels (IL-6, IL-10, and TNF-alpha) were observed in pts with CRS. Immunohistological analysis of malignant lymph node tissue demonstrated a decrease of CD20 expression in responding pts; among the responders, subsequent relapse was associated with either maintenance of CD20 expression or further CD20 loss, suggesting antigen-dependent and independent disease escape mechanisms. Conclusions REGN1979 displays efficacy and an acceptable safety profile in pts with R/R B-NHL. Most TR-TEAEs were IRR/CRS and have been well managed with supportive care. No significant neurological toxicity has been observed. At doses of 5-27 mg of REGN1979, the preliminary ORR was 100% in pts with FL Grade 1-3a and 40.0% in pts with DLBCL. This promising efficacy warrants further clinical investigation. Disclosures Bannerji: Regeneron Pharmaceuticals, Inc.: Consultancy; AbbVie, Inc.: Consultancy. Arnason:Regeneron Pharmaceuticals, Inc.: Consultancy. Advani:Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; Janssen Pharmaceutical: Other: Institutional Research Support; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Pharmacyclics: Other: Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Millenium: Other: Institutional Research Support; Gilead/Kite: Other: Consultancy/Advisory Role; Infinity: Other: Institutional Research Support; Merck: Other: Institutional Research Support; Forty Seven, Inc: Other: Institutional Research Support; Cell Medica: Other: Consultancy/Advisory Role; Agensys: Other: Institutional Research Support; Celgene: Other: Institutional Research Support; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support; Kura: Other: Institutional Research Support; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Kyowa: Other: Consulting/Advisory Role; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Autolus: Other: Consultancy/Advisory Role; AstraZeneca: Other: Consultancy/Advisory Role. Brown:Acerta / Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Pharmacyclics: Consultancy; Celgene: Consultancy; Genentech: Consultancy; TG Therapeutics: Consultancy; Morphosys: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Abbvie: Consultancy; Gilead: Consultancy, Research Funding; Sun Pharmaceutical Industries: Research Funding; Sunesis: Consultancy; Loxo: Consultancy; Beigene: Membership on an entity's Board of Directors or advisory committees; Invectys: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Consultancy; Boehringer: Consultancy. Allan:Genentech: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy. Ansell:Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Merck & Co: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Celldex: Research Funding; Takeda: Research Funding; Pfizer: Research Funding. O'Brien:Kite Pharma: Research Funding; Aptose Biosciences Inc.: Consultancy; Pharmacyclics: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Astellas: Consultancy; Sunesis: Consultancy, Research Funding; Alexion: Consultancy; Amgen: Consultancy; TG Therapeutics: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Vaniam Group LLC: Consultancy; Regeneron: Research Funding; Janssen: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; Acerta: Research Funding; Gilead: Consultancy, Research Funding. Chavez:Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Research Funding; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Humanigen: Consultancy. Lowy:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Charnas:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Sternberg:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ambati:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Adriaens:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Ufkin:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Yan:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Li:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Navarro:Regeneron Pharmaceuticals, Inc.: Employment. Gasparini:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Jankovic:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Fiaschi:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Zhang:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Hamon:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Thurston:Regeneron Pharmaceuticals, Inc.: Employment, Equity Ownership. Topp:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding.

Description: Background: The Early T-cell precursor (ETP) variant of acute lymphoblastic lymphoma/leukemia (ALL) is a recognized high risk variant, recognized by the absence of CD1a, with aberrant myeloid antigen expression (CD13, CD33, CD117, and CD34), and frequent absence of CD4 or CD8. Treatment intensification may improve outcome in this subset. We undertook a multi-center retrospective analysis to explore clinical features, treatment exposure, and outcomes in ETP ALL as compared to non-ETP variants. Methods Adult T-ALL/T-LBL cases were compiled from 3 high volume cancer centers between the years 2003-2015. Data collected included patient demographics, tumor characteristics (white count at diagnosis, flow cytometry, FISH, cytogenetics, bone marrow involvement), treatment regimens and patient outcomes. ETP cases were defined as definite (CD1a-/CD8-/myeloid+) or probable (CD1a unk/CD8-/myeloid+, or CD1a-/myeloid+ with CD4+ and/or CD8+). All other cases were defined as non-ETP. Demographic data were compared using independent t-test assuming non-equal variance. OS and PFS were calculated from diagnosis and compared by Kaplan Meier and log-rank testing. Results Among 95 cases, 33 met criteria for definite/probable ETP (35%). OS and PFS data were indistinguishable between these groups (p=0.24, p=0.34), and were subsequently analyzed as a single group. Within the ETP group, no factors were associated with OS, including histology (CD1a+ vs unk, CD3cyt vs CD3sur, CD5dim vs CD5+, CD1a+/13+ vs CD1a+/13-, or CD13, CD33, CD117, CD34, & TdT status), marrow blast burden, peripheral blast burden, white blood cell count (wbc), hemoglobin (hgb), platelet count (plt), cytogenetics/FISH status, chemotherapy choice, or allogeneic transplant (in CR1 or at any time). With regards to PFS, only the inclusion of asparaginase with induction was associated with outcome (p=0.009), while all other covariates failed to show any significance. The ETP group was compared with the non-ETP subset (table 1). ETP were more likely to abuse marijuana, possibly reflecting unrecognized pesticide exposure, and were more likely to abnormalities of chrom 5 & 7. ETP trended towards lower response and higher rate of relapse, with lower PFS. Comparison of OS was not significant, likely related to small numbers (5y OS 37% vs 22%, figure 1). Non-ETP failed to show PFS benefit with frontline asparaginase, otherwise no treatment differences were apparent. Conclusions In this muti-center cohort we were able to identify and characterize ETP cases, confirming poor outcomes. Improvement in PFS among ETP patients treated with frontline asparaginase warrants attention and prospective confirmation. Unfortunately, OS remains poor independent of treatment or receipt of allogeneic transplant, suggesting a critical need remains for development and study novel therapies. Table 1. ETP Non-ETP p-value Median Age 37.45 34.74 0.42 Male 82% 66% 0.89 FamilyHx of Lymph/Leuk 21% 8% 0.112 FamilyHx of Ca 42% 25% 0.09 THC 24% 5% 0.021 P blasts 40% 28% 0.158 〉25% M blasts 30% 55% 0.0571 WBC 78.45 76.55 0.948 wbc〉100 24% 24% 0.995 Hgb 10.72 11.78 0.148 hgb

Description: Introduction: One of the main complications of adoptive T cell therapy (ACT) is the en-masse activation of tumor-reactive T cells inducing a large release of cytokines followed by activation of other immune cells leading to adverse events. These are classified as a cytokine release syndrome (CRS) or neurotoxicity described as a CAR T Related Encephalopathy Syndrome (CRES). Several biomarkers have been associated with CRS and/or neurotoxicity such as LDH, ferritin and CRP. Cytokines have also been associated with CRS and and/or CRES, but present approaches rely on retrospective study of collected biomarkers. Here, we report the results of cytokine analysis using a point of care (POC) device to predict immune-related toxicities in patients with relapsed/refractory (R/R)DLBCL treated with axicabtagene ciloleucel (axi-cel). Methods: Patients with R/R DLBCL treated with commercial axi-cel were included in this study. Baseline serum samples were collected prior to lymphodepleting chemotherapy and then daily during hospitalization. To select which cytokines to monitor, we retrospectively analyzed 38 serum cytokines in a cohort of 53 patients with R/R B cell acute lymphoblastic leukemia (B-ALL) who were treated with 19-28z CAR T cells. The patients were divided into those requiring treatment with tocilizumab and/or steroids versus those who did not require treatment. We observed several cytokines, including IL-2, IL-6, IL-15 and IFNg, which were significantly elevated in patients with CRS and/or CRES requiring treatment (Figure 1a). Based on this analysis and results of published studies, eight serum proteins were selected in our study including IL-1b, IL-2, IL-6, IL-15, IFNg, TNFa, and angiopoietin-1 &2. We monitored these proteins using a POC device that allows for rapid daily monitoring with a turnaround time of two hours. We established that the results from the POC device strongly correlate with a current gold standard device(Luminex), which has a typical two day turn around time. CRS and CRES were prospectively graded using revised Lee criteria (Lee et al Blood 2014) and the CARTOX group (Neelapu et al. NRCO 2017) respectively by an experienced clinical team and confirmed by chart review retrospectively. Results: A total of 20 patients with R/R DLBCL treated with commercial axi-cel were identified. Median age 64 years ( range 43-73) with 80% male.In our cohort, grades 1-3 CRS were observed in 45%, 40% and 5% respectively. There were no observed grade 0 or grade 4 CRS. There were two patients (10%) who died in the setting of severe toxicity. Patients with grade 5 CRS had higher levels of IL-6 and angiopoietin 2/angiopoietin 1 ratio at day one, which correlated with severity of toxicity r=0.52 (p= 0.039) , and r=0.53 (p=0.033) respectively (Fig. 1b). Furthermore, patients with high grades CRS had elevated levels of IL-15 at day seven (r=0.83, p=0.006). The majority of patients (55%) had grade 1-2 CRES.There were no significant correlations between serum cytokine levels and CRES or between those who required tocilizumab/steroids vs. those who did not, likely due to the small sample size. In select cases, daily monitoring of cytokines using the POC device provided clinical insight that wasn't evident from standard biomarkers. For example, one patient who developed delayed CRS had high serum levels of IL-6 but did not have elevated levels of CRP(Fig.1c). Discussion: In this analysis of 20 patients, we observed a correlation between severe CRS and elevated serum cytokine levels of IL-6 and angiopoietin 2/angiopoietin 1 ratio at day one suggesting that these biomarkers may be utilized to predict severe toxicity in patients treated with ACT. While this study is limited by small sample size, our observations correlate with previously published biomarkers data in patients enrolled in clinical trials. To our knowledge this is the first reported cytokine data using commercial axi-cel. Monitoring of cytokines using a POC device is feasible and will be useful clinically. High risk patients may be identified early and help guide intervention in real time, for example day one elevated IL-6 levels might inform earlier use of tocilizumab. We continue to enroll patients to validate cytokines as predictive biomarkers with the goal of informing the development of preventative strategies to mitigate CAR T cell therapy immune related adverse events. Disclosures Locke: Cellular BioMedicine Group Inc.: Consultancy; Kite Pharma: Other: Scientific Advisor; Novartis Pharmaceuticals: Other: Scientific Advisor. Brentjens:Juno Therapeutics, a Celgene Company: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Park:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; Kite Pharma: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Shire: Consultancy. Davila:Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Description: Background: ALL is an aggressive hematologic malignancy traditionally treated with intensive inpatient-based chemotherapy, which can require prolonged hospitalizations both for the delivery of chemotherapy and subsequent side effects including infectious complications and cytopenias. In addition, chemotherapeutic CNS prophylaxis further intensifies the regimen and the logistical challenges associated with its delivery. While inpatient delivery of chemotherapy may mitigate some of the logistical and clinical challenges, as healthcare moves towards a value oriented approach, delivery of these services in an outpatient setting that could lower the cost of care may offer significant value to the patient and institution. We report on our institutional experience of shifting the commonly used Hyper-CVAD regimen ("Arm-A") into the outpatient setting. Methods: Hyper-CVAD consists of an "A" Arm (Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone) and a "B" Arm (Methotrexate and Cytarabine). From 5/2014-6/2015, 24 patients received Hyper-CVAD Arm-A for ALL (18 patients) or high-grade lymphoma (6 patients) in the outpatient setting. Median age was 35.7 years (range of 20-67). A total of 50 cycles of HyperCVAD Arm-A were delivered to these 24 patients: an average of 2.1 cycles per patient. The majority of patients (n=21, 88%) received the first cycle of Hyper-CVAD as inpatient. Doses and schedule of chemotherapy as follows: Cyclophosphamide 300mg/m2/dose IV over 3 hours Q12 hours x 6 on days 1-3, Vincristine 2mg IV over 10 minutes x 1 on day 4, Doxorubicin 50mg/m2 IV over 15 minutes x1 on day 4, Dexamethasone 40mg PO daily on days 1-4 and 11-14. Modifications to the regimen to facilitate outpatient administration included the delivery of cyclophosphamide over 1 hour in the morning and evening doses (reduced from three hours) with evening cyclophosphamide delivered approximately 10 hours after morning dosing. Additionally, on days 1-3, each patient received mesna via a 24 hour ambulatory pump with pump change each day during morning chemotherapy sessions. Daily urinalyses were performed. Cost of regimen delivery was estimated through work with our financial analysis group and includes expected gross charges for chemotherapy and any hospitalization associated with the delivery of chemotherapy. Results: None of the 24 patients died during the period of outpatient administration of Hyper-CVAD. In addition, there were no occurrences of hemorrhagic cystitis. While there were predictable complications, including infections that required hospitalization, these occurred after completion of chemotherapy, during the period of neutropenia. Only 1 patient (4%) required admission for chemotherapy mid-cycle due to concerns for compliance with outpatient therapy. Overall, we estimated that 200 hospital days were saved over the examined time period. Administration of a cycle of Hyper-CVAD, Arm-A in the outpatient setting was accompanied by an approximate 13% reduction in gross charges ($2541). Thus, over the course of this 13 month time period, administration of outpatient Arm-A of HyperCVAD was accompanied by an estimated reduction in the cost of care of $127,050 amongst 24 patients. Conclusion: Outpatient administration of Arm A of Hyper-CVAD was feasible, safe and well tolerated, while significantly reducing the overall cost of care associated with its delivery. Future efforts and larger studies to transition traditional inpatient chemotherapy regimens to the outpatient setting appear warranted. Disclosures Shah: Acetylon: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Speakers Bureau; Spectrum: 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, Speakers Bureau; PLexus Communications: Honoraria; Bayer: Honoraria; Rosetta Genomics: Research Funding; Seattle Genetics: Research Funding. Komrokji:Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau; Incyte: Consultancy; Celgene: Consultancy, Research Funding. Lancet:Amgen: Consultancy; Kalo-Bios: Consultancy; Seattle Genetics: Consultancy; Celgene: Consultancy, Research Funding; Boehringer-Ingelheim: Consultancy; Pfizer: Research Funding.