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Purpose: Axicabtagene ciloleucel (axi-cel) is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory diffuse large B-cell lymphoma. Bridging therapy may be required for lymphoma control during the manufacturing interval between collection of autologous T cells and final CAR T product administration. The optimal bridging therapy is not known and patients are often chemorefractory. We present a case series of patients receiving radiation as a bridge to axi-cel.Methods and Materials: Between December 2017 and October 2018, 12 patients were intended to receive bridging radiation before axi-cel. The group was characterized by highly aggressive disease including 6 of 12 with "double hit" lymphoma and 6 of 12 with disease ≥10 cm in diameter. All patients received 2 to 4 Gy/fraction to a median dose of 20 Gy (range, 6-36.5 Gy). Half of patients received either 30 Gy in 10 fractions or 20 Gy in 5 fractions. Seven patients received concurrent chemotherapy. Eleven patients underwent axi-cel infusion and one did not. Median follow-up was 3.3 months (range, 1.1-12.0 months).Results: No significant toxicities were identified during bridging radiation, and no patient experienced in-field progression of disease before axi-cel infusion. One patient experienced abdominal pain, which resolved after dose reduction. Two patients had out-of-field progression of disease during the bridging period. After axi-cel infusion, 3 of 11 patients (27%) experienced severe cytokine release syndrome or neurotoxicity. At 30 days, the objective response rate was 81.8% (11 of 12 evaluable; 1 stable disease, 1 out-of-field progression), with complete response in 27% (3 of 11). At last follow-up, the best objective response rate was 81.8%, with a complete response attained in 45% (5 of 11). Lymphocyte counts decreased slightly in 10 of 12 patients during radiation (median, 0.25 k/uL).Conclusions: Radiation (with or without concurrent chemotherapy) can be safely administered as a bridge to axi-cel in high-risk lymphoma. Caution should be taken if irradiation is started before apheresis, and lymphocyte counts should be monitored closely throughout. Future investigation is warranted to optimize the use of bridging radiation before CAR T therapy. [ABSTRACT FROM AUTHOR]

Abstract: Cardiopulmonary bypass (CPB) during cardiac surgery can involve deliberate hypothermia of the systemic (22-36°C) and coronary circulations (as low as 8-12°C). Adverse sequelae of cold-active antibodies have been feared and reported under such conditions, and some centers thus elect to screen for cold agglutinins before CPB. We reviewed the literature on cold agglutinins in cardiac surgery and described the yields and effects of cold agglutinin screening (CAS) in 14900 cardiac surgery patients undergoing CPB over 8 years at a single institution. Cold agglutinin screening was positive in 47 cases (0.3%), at an annual testing cost of $17000 CAD. The response of the surgical team to the preoperative discovery of a cold agglutinin was variable, with CPB modified to avoid hypothermia in approximately one-third of cases. In patients discovered to have a positive CAS, postoperative intensive care unit and hospital length of stay were marginally increased (54.6 vs 42.8 hours, P = .02; 7 [6-14] vs 7 [5-9] days, P = .04). However, the composite of mortality or severe morbidity (stroke, myocardial infarction, dialysis, low output syndrome, sepsis, and deep vein thrombosis) was not significantly different (14.9% vs 9.2%, P = .2). Antibody verification found that only 43% of positive CAS patients had true cold agglutinins (20 patients). Furthermore, the rate of adverse events was low in both CAS-positive and true-positive cold agglutinin patients undergoing CPB and cardiac surgery. Finally, modification of CPB to attenuate hypothermia did not decrease adverse events. Based upon historical and local data, preclinical CAS is cost-substantial and nonspecific. Cold agglutinin screening does not promote an algorithm of care that meaningfully improves patient CPB outcomes. [ABSTRACT FROM AUTHOR]

CAR T cells have been extensively investigated using constructs targeting CD19+ B cells for lymphoid malignancies demonstrating efficacy (Neelapu NEJM 2018; Schuster NEJM 2018). One of the main challenges of adoptive T cell therapy are immune mediated toxicities of cytokine release syndrome (CRS) and neurotoxicity (NT). Despite impressive objective response rates, durable responses are only seen in approximately 40% of patients treated in the pivotal axicabtagene ciloleucel (axi-cel) and tisagenlecleucel trials, highlighting the need for better understanding of the mechanisms of toxicity and efficacy. We aimed to evaluate the association of early biomarkers with severe toxicity and day 90 outcomes in patients treated with commercial axi-cel in a real world setting. Seventy-five patients treated with commercial axi-cel were included in this analysis. Baseline characteristics are summarized in Table 1. Patient serum samples were collected at baseline (within 30 days of conditioning chemotherapy), and then daily thereafter starting at the day of axi-cel infusion. Serum cytokine samples were analyzed using the Ella multiplex assay system. Cytokines analyzed include IL1b, IL2, IL6, IL15, TNFa, IFNg, Angiopoietin 1 and 2, as well as CRP and ferritin. Toxicities were graded daily using ASTCT consensus guidelines and retrospectively confirmed. Outcomes were evaluated at day 90 by the treating physician according to the International Working Group Response Criteria for Malignant lymphoma. P values were calculated using Wilcoxon rank sum test. We observed that baseline levels of CRP (p=0.0018) and Angiopoietin 2/1 ratio (p=0.0092) were associated with grade ≥3 [n=16] neurotoxicity Figure 1A-B). Baseline elevated levels of CRP (p=0.0413) and Ferritin (0.0264) were associated with more grade ≥3 CRS [n=16] (Figure 1C-D). Baseline elevated levels of CRP(p=0.0016), ferritin(p=0.0096) and IL6 (p=0.0029) were associated with poor outcomes at D90 defined as stable disease, progressive disease or death (Figure 1E-G). We demonstrate that baseline biomarker profile can identify patients at highest risk of developing severe toxicity and/or and treatment resistance highlighting the need to validate these findings in prospective studies. Patients in this poor outcome cohort may benefit from clinical trials evaluating prophylactic agents or more combination therapies to ameliorate severe toxicities or increase response rates. [ABSTRACT FROM AUTHOR]

Purpose: Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, most treated patients relapse. Patterns of failure after CAR T have not been previously characterized, and may provide insights into the mechanisms of resistance guiding future treatment strategies.Methods and Materials: This is a retrospective analysis of patients with R/R large B-cell lymphoma who were treated with anti-CD19 CAR T at a National Cancer Institute-designated Comprehensive Cancer Center between 2015 and 2019. Pre- and posttreatment positron emission/computed tomography scans were analyzed to assess the progression of existing (local failures) versus new, nonoverlapping lesions (de novo failures) and identify lesions at a high risk for progression.Results: A total of 469 pretreatment lesions in 63 patients were identified. At a median follow-up of 12.6 months, 36 patients (57%) recurred. Most (n = 31; 86%) had a component of local failure, and 13 patients (36%) exhibited strictly local failures. Even when progressing, 84% of recurrent patients continued to have a subset of pretreatment lesions maintain positron emission/computed tomography resolution. Lesions at a high risk for local failure included those with a diameter ≥5 cm (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.55-3.55; P < .001), maximum standardized uptake value ≥10 (OR, 2.08; 95% CI, 1.38-3.12; P < .001), or those that were extranodal (OR, 1.49; 95% CI, 1.10-2.04; P = .01). In the 69 patients eligible for survival analysis, those with any lesion ≥5 cm (n = 46; 67%) experienced inferior progression-free survival (hazard ratio, 2.41; 95% CI, 1.15-5.04; P = .02) and overall survival (hazard ratio, 3.36; 95% CI, 1.17-9.96; P = .02).Conclusions: Most patients who recur after CAR T experience a component of local progression. Furthermore, lesions with high-risk features, particularly large size, were associated with inferior treatment efficacy and patient survival. Taken together, these observations suggest that lesion-specific resistance may contribute to CAR T treatment failure. Locally directed therapies to high-risk lesions, such as radiation therapy, may be a viable strategy to prevent CAR T failures in select patients. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T.Objectives: The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T.Methods: The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death.Results: The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade ≥2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade ≥2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade ≥2 CRS (31% patients with grade ≥2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab.Conclusions: Among adults, cardiac injury and CV events are common post-CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events. [ABSTRACT FROM AUTHOR]

B-cell homeostasis plays an important role in chronic GVHD (cGVHD). The safety and feasibility of anti-CD20 directed B-cell therapy with ofatumumab and glucocorticoids (GC) were previously established in a phase I trial. A total of 38 adult patients (pts) with moderate/severe cGVHD were enrolled in phase II trial at 3 academic US centers (02/2014-08/2018). Ofatumumab was given at 1000 mg IV on days 0 and 14 of initial 1 mg/kg/day prednisone (or equivalent) therapy. Primary endpoint was the overall (complete and partial) response rate (ORR) at 6 months as reported by the physician (MD). Baseline data are summarized in Table. Six-month ORR for 32 evaluable pts was 62.5% (95%CI, 44-79%) by MD report (15.6% CR; 46.9% PR) and by NIH2014 criteria (9.4% CR; 53.1% PR) with good inter-rater reliability (Cohen's kappa=0.73; discordant responses n=4). Given historical benchmark ORR of 60% at 6 months, the trial did not reach its primary endpoint (p =0.4) of 20% improvement with ofatumumab. Subsequent ORR per MD and NIH2014 were 42% and 31% at 12 months (kappa=0.6) and 36% and 32% at 24 months (kappa=0.9). GC discontinuation was successful in 45% and 54% of pts at 12 and 24 months (Figure 1A). Median follow up of survivors was 24 months (range, 0.7-46). Two-year OS and PFS were 74% and 72%. Failure-free survival (FFS) - composite outcome with death, relapse, and second-line immune suppression as events - was 53% at 12 months and 39% at 24 months. Second-line therapy was the most common failure event (13/22, Figure 1B). 14 non-fatal possibly related AEs occurred in 11 pts, including 5 SAEs in 3 pts. 17 infusion-related AEs (all ≤Gr2) occurred, but resolved with symptom management. Bacterial (13 events), fungal (8), and viral (26) infections were observed in 29%, 13%, and 40% of pts, respectively. 9 deaths occurred within 2 years, none of which was deemed related to study therapy. This multicenter phase II trial did not demonstrate statistical difference in 6 month ORR with ofatumumab+GC vs. GC-based historical benchmark in the frontline therapy of cGVHD. Data on predictors of response, patient-reported outcomes, and immune reconstitution will be presented at the meeting. [ABSTRACT FROM AUTHOR]

Hypofibrinogenemia can occur after Chimeric Antigen Receptor (CAR) T-cell therapy and is sometimes associated with cytokine release syndrome. Hypofibrinogenemia is associated with increased risk of bleeding as well as thrombosis. Limited literature exists on the incidence, complications and management of hypofibrinogenemia after CAR T-cell therapy. We analyzed medical records on 148 patients who received CD19-directed CAR T-cell therapy for large B-cell lymphomas between 05/2015 and 09/2019. All patients who had at least one serum fibrinogen level measured in the first 30 days after CAR T-cell infusion were included in the analysis. All patients with serum fibrinogen < 200 mg/dL [lowest normal value] had data collected on abnormalities in other coagulation parameters including PTT, PT, INR at the time of nadir serum fibrinogen level. Out of 148 patients, 35 had at least one serum fibrinogen level measured in the first 30 days after CAR T-cell infusion. Nadir serum fibrinogen was < 200 mg/dl in 15/35 patients: 0-100 mg/dl in 9/15 and 100-200 mg/dl in 6/15. At the time of nadir fibrinogen level, 2/15 patients had abnormalities seen in the other 3 coagulation parameters. Of the 15 patients that had serum fibrinogen level < 200 mg/dl, four had a bleeding event and one had a thrombotic event within first 30 days after CAR T-cell infusion but none of these patients had a low fibrinogen level at the time of the bleed. Given concern for increased risk of bleeding, patients with serum fibrinogen level less than 100 mg/dl were given cryoprecipitate infusions. Details of the abnormalities in the coagulation parameters are highlighted in the table. This study describes in detail, hypofibrinogenemia seen in patients treated with CD19-directed CAR T-cell therapy in lymphoma. None of the patients experienced a major bleeding or thrombotic event with low serum fibrinogen level. These descriptive data may be used by clinicians to inform their management of hypofibrinogenemia seen in CAR T-cell patients. [ABSTRACT FROM AUTHOR]

In patients with lymphoma, third space fluid accumulations may develop or worsen during cytokine release syndrome (CRS) associated with chimeric antigen receptor (CAR) T-cell therapy. Pre-existing symptomatic pleural effusions were excluded by the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel) for large B cell lymphoma (LBCL) and variants. The optimal management of effusions that develop before or after axi-cel infusion in LBCL is unknown. We performed a single center retrospective study evaluating 148 patients receiving CD19 CAR T-cell therapy for LBCL between 05/2015 and 09/2019. We identified all patients who developed pleural, pericardial and peritoneal effusions before (pre-CAR-T) or during the first 30 days after CAR T-cell infusion (post-CAR-T). Clinically relevant effusions were considered symptomatic based upon physician documentation. Total effusions and symptomatic effusions were noted in 24% (36/148) and 18% (27/148) of patients, respectively. Among 27 patients with symptomatic effusions, 59% (16/27) were pre-CAR-T effusions, 52% (14/27) persisted after day 30, and 44% (12/27) were malignant effusions. Overall, 67% of symptomatic effusions (18/27) were managed with diuretics, 44% (12/27) with a therapeutic thoracentesis or paracentesis and 33% (9/27) were observed with only supplemental oxygen provided. Six patients required pleural or abdominal catheters with a median indwelling duration of 54 (range, 29, 202) days, although 2 of these patients passed away with these indwelling catheters. Among symptomatic effusions developing only post-CAR-T (n=11), time to onset of effusion was median of 5 (range, 2-11) days and none of these patients required interventional drainage. Table 1 differentiates between effusions based on whether they were present (n = 19) or not (n = 17) prior to CAR T cell infusion. Nearly half of all effusions diagnosed in patients receiving CAR T cell therapy develop after infusion but most can be medically managed. Patients with pre-CAR-T effusions may require procedural drainage or indwelling catheters, as these effusions may persist beyond the acute CRS period. [ABSTRACT FROM AUTHOR]

Post-transplant cyclophosphamide (PTCY) is being increasingly used for graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT) across various donor types. However, immune reconstitution after PTCY-based vs. conventional GVHD prophylaxis has not been well studied. We evaluated the pace of immune reconstitution (CD4+ T-cell, CD8+ T-cell, NK-cell and B-cell) at 3 months, 6 months and 1 year post-HCT in 583 adult patients receiving myeloablative (n=223) or reduced intensity conditioning (n=360) HCT (2012-2018). Haploidentical (Haplo; n=75) and 8/8 HLA-matched unrelated (MUD, n=508) donor types were included. GVHD prophylaxis was PTCY-based in 75 Haplo and 38 MUD (MUD-PTCY) HCT, while tacrolimus/methotrexate (TAC/MTX) was used in 89 and TAC/Sirolimus (TAC/SIR) in 381 MUD HCT. Clinical outcomes including viral infections, non-relapse mortality (NRM) and overall survival (OS) were compared across all four treatment groups. The recovery of absolute total CD4+ T-cell count after Haplo-PTCY and MUD-PTCY was significantly lower compared to MUD TAC/MTX or MUD TAC/SIR throughout 1 year of HCT (Figure). In contrast, CD19+ B-cell recovery at 6 months and thereafter was more rapid after Haplo-PTCY and MUD-PTCY HCT in comparison to MUD TAC/MTX and MUD TAC/SIR. In subgroup analysis compared to MUD TAC/MTX HCT, total CD8+ T-cell or NK-cell recovery was not significantly different after Haplo-PTCY or MUD-PTCY HCT. However, patients receiving MUD TAC/SIR vs. MUD TAC/MTX had significantly slower reconstitution of total CD8+ T-cells up to 6 months and CD19+ B-cells at 1 year of HCT, but no significant differences in CD4+ T-cell or NK-cell recovery. The distribution of recipient CMV serostatus was similar in all four groups: 72% in Haplo-PTCY, 62 % in MUD-PTCY HCT, 68% in MUD TAC/MTX and 63% in MUD TAC/SIR (p =0.11). Cumulative incidence of CMV reactivation/infection at 1-year of HCT was higher in patients receiving Haplo-PTCY (39.6%) or MUD TAC-MTX (37.7%) compared to those receiving MUD-PTCY (27.0%) or MUD TAC/SIR (22.8%; p <0.01). Whereas the incidence of EBV reactivation/infection was lower in patients receiving PTCY-based GVHD prophylaxis (5.2% in Haplo-PTCY and 8.1% in MUD-PTCY) as compared to patients receiving MUD TAC/MTX (19.7%) or MUD TAC/SIR (20.5%, p <0.01). The incidences of HHV6, BK- and other viruses were similar between the groups. Overall, the treatment groups had comparable NRM (p =0.27) and OS outcomes (p =0.78). Our data demonstrate that the pattern of immune reconstitution after HCT is different after PTCY-based vs. conventional GVHD prophylaxis with delayed total CD4+ T-cell but more rapid B-cell recovery after PTCY-based GVHD prophylaxis. The rates of CMV and EBV viral infections were different across the donor types. However, these differences had no significant influence on NRM or survival after HCT. [ABSTRACT FROM AUTHOR]

Cancer associated venous thrombo-embolism (VTE) constitutes major cause of mortality and morbidity in patients with hematological malignancies. There is limited data on the incidence and management of VTE in patients receiving chimeric antigen receptor (CAR) T-cell therapy. We performed a single center retrospective study of 148 patients receiving CD19-directed CAR T-cell therapy for aggressive B-cell lymphomas between 05/2015 and 09/2019 to evaluate the incidence and management of known and new VTE phenomenon between day 0-100 after CAR T-cell infusion. Prophylaxis with anticoagulation (AC) was utilized in 4% (6/148) of patients between day 0-100 after CAR T-cell infusion. 19% (28/148) had known VTE prior to CAR T-cell infusion and 50% (12/28) of these were still on AC at the time of infusion. Of those on AC for prior VTE at the time of infusion, 50% (6/12) had it held between day 0-100 after CAR T-cell infusion due to low platelet count or risk of bleeding, while the remainder continued without interruption. A new episode of VTE, between day 0-100, occurred in 11% (16/148) of patients. None of these patients had previous known VTE. Of these, 75% (12/16) started therapeutic AC, however 42% (5/12) had AC held before day 100 after CAR T-cell infusion due to low platelet count or risk of bleeding. None of the patients that continued therapeutic AC in the 2 cohorts had a bleeding event. Details of the thrombotic events and management with AC are shown in the table. This is the first study to our knowledge that describes in detail the incidence and characteristics of VTE and use of AC in lymphoma patients receiving CAR T-cell therapy. Most patients were managed with AC without complications of recurrent VTE or bleeding. [ABSTRACT FROM AUTHOR]

Haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplant cyclophosphamide (PTCy) is increasingly offered as a curative treatment for patients with hematological malignancies. In a recent registry study (Bashey et al. JCO 2017), peripheral blood (PB) as a graft source compared to bone marrow reduced the risk of relapse but increased acute and chronic GVHD after haplo-HCT with PTCy in combination with calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF). In this phase II trial we aimed to assess the efficacy of Sirolimus (Sir) in combination with PTCy and MMF as a CNI-free GVHD prophylaxis after PB haplo-HCT (NCT03018223). The primary end point was the cumulative incidence of grade II-IV acute GVHD at day 100 after HCT. With 32 evaluable patients enrolled, the study had a 90% power (α = 0.1) to demonstrate a reduction in 100-day grade II-IV acute GVHD from the historical benchmark of 40% (haplo-HCT and PTCy/Tac/MMF) to 20%. Sir was administrated from days +5 to +90 at target level of 8-14 ng/ml, followed by taper by day +180 in the absence of acute GVHD. A total of 32 patients with hematological malignancies were treated on trial 2/2017- 8/2018. The median age at HCT was 50 years (range, 23-75) and 59% of patients were racial/ethnic minorities. AML (50.0%) was the most common indication for HCT. The majority (66%) received myeloablative Fludarabine (Flu) and Busulfan (AUC of 5300), while 34% received non-myeloablative Flu/Cy/TBI 200 cGy. There were no graft failure events and the median time of neutrophil engraftment was 17 days (range, 12 - 30). With a median follow-up of 15.4 months, the primary endpoint was met with day 100 grade II-IV acute GVHD cumulative incidence of 18.8% (95% CI 7.5 - 34.0; grade III-IV = 9.4%). The cumulative incidence of 1-year NIH moderate/severe chronic GVHD was 20.0% (95% CI 7.9-36.0) (Figure). Only 3 patients required systemic glucocorticoids for chronic GVHD therapy. At last follow up, all immunosuppression was successfully discontinued in 43% (n=12) of all surviving study patients. The 1-year probability of non-relapse mortality was 19.7% (95% CI 7.8 - 35.5), relapse was 23.7% (95% CI 10.2 - 40.4), disease-free survival was 56.6% (95% CI 41.3 - 77.7) and overall survival was 70.2% (95% CI 55.5 - 88.6) for the entire cohort. These data demonstrate that PTCy/Sir/MMF GVHD prophylaxis effectively prevents grade II-IV acute GVHD after PB haplo-HCT and results in successful hematopoietic engraftment. Furthermore, the initial chronic GVHD, relapse and survival outcomes appear favorable. These findings warrant prospective comparison of PTCy/Sir/MMF with PTCy/Tac/MMF after PB haplo-HCT. [ABSTRACT FROM AUTHOR]

Background A cytokine release syndrome (CRS) or neurotoxicity described as a chimeric antigen receptor (CAR) T Related Encephalopathy Syndrome (CRES) is one of the main complications while CD19 CAR T has been successful in relapsed/refractory (R/R) B cell malignancies. CRS and/or CRES have been associated with standard biomarkers such as CRP and ferritin but also with cytokines. We report the results of cytokine analysis using a point of care (POC) device to predict immune-related toxicities in patients with R/R DLBCL treated with axicabtagene ciloleucel (axi-cel). Methods Patients treated with commercial axi-cel in Moffitt Cancer Center were included in this study. Serum samples were collected prior to lymphodepleting chemotherapy at baseline and then during hospitalization. Based on 38 serum cytokineś analysis in B-cell acute lymphoblastic leukemia patients treated with 19-28z CAR T and results of published studies, 8 serum proteins were selected to monitor. CRS and CRES were prospectively graded by Lee criteria and CARTOX respectively. Results 41 patients were identified. Median age was 64 years old (76% male). Non-severe (grade 0-2) and severe (grade 3-5) CRS were observed in 93% and 7% respectively while non-severe and severe CRES were observed in 71% and 29% respectively. 2 patients died in the setting of severe toxicity. Baseline CRP, ferritin, IL-6 levels were significantly elevated in the patients who developed severe CRS and/or CRES. Baseline angiopoietin-2/angipoietin-1 ratio (ANG-2/1) was also correlated with severe CRES. In select cases, monitoring of cytokines provided clinical insight that wasńt evident from standard biomarkers. Conclusions We observed correlations between severe toxicities and elevated serum cytokine levels of baseline IL-6 and ANG-2/1 suggesting that these biomarkers may be utilized to predict severe toxicity in patients treated with CAR T. Monitoring of cytokines using a POC device is feasible and would be useful clinically. [ABSTRACT FROM AUTHOR]