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Introduction Chimeric antigen receptor (CAR) T cell (CART) therapy has shown to be a new and very promising therapeutical method in patients with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). The investigator-initiated Heidelberg-CAR-T-cell-trial 1 (HD-CAR-1) evaluates both efficacy and safety of escalating doses of 3 rd-generation CD19-directed CARTs comprising CD28 and 4-1BB as costimulatory molecules in patients with r/r ALL and NHL. Leukapheresis, manufacturing, administration, patient monitoring and follow-up were all conducted in-house at the Heidelberg University Hospital. Methods Treatment was conducted with escalating doses of autologous 3 rd-generation CARTs after lymphodepletion with fludarabine (90 mg/m 2) and cyclophosphamide (1,500 mg/m 2) in patients with r/r acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), or Non-Hodgkin's lymphoma (NHL), with subtype including diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL) or mantle cell lymphoma (MCL). Treatment efficacy as well as occurrence of toxicities, such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections or cytopenia, were evaluated. Following prior results regarding dose-dependent efficacy and excellent toxicity profile with dose levels (DL) I, II and III (10 6, 5×10 6 and 20×10 6 CARTs/m 2), a trial amendment was approved for treatment of patients with higher CART doses (DL IV, V and VI: 5x10 7, 10x10 7 and 20x10 7 CARTs/m 2). Results Overall, screening was performed for 32 patients. Two patients were considered screening failures due to rapidly progressive disease (PD) and uncontrolled hepatitis B infection, respectively; leading to 30 patients enrolled in the study. The HD-CAR-1 product was given to 27 patients (12 patients with ALL, four with CLL, four with MCL, five with DLBCL, and two with FL) in different dose levels (six patients with DL I, six patients with DL II, eight patients with DL III, 5 patients with DL IV, 2 patient with DL V). The CART product was not given to two patients due to PD and lethal septic complication, respectively. Severe CAR-T toxicity was rare, as only two patients developed CRS ≥ III°. Both patients received treatment with tocilizumab, while one was additionally treated with steroids. No ICANS ≥ III° were reported in the study. 54% of patients achieved a complete response (CR) with an overall response rate (ORR) of treated patients of 65%. In a subgroup response analysis, an ORR of 92% (83% CRs) with 50% of all patients achieving MRD-negative CR was seen in ALL patients. In the NHL/CLL cohort, an ORR of 43% and a CR rate of 29% were observed. Figure 1 displays OS and PFS results till the end of study (EOS, day +90). Conclusion Academic CART production was feasible for all enrolled patients. Patients responded clinically to treatment and CARTs displayed a highly favorable safety profile. Overall, HD-CAR-1 accounts for clinical evaluation of 3 rd generation CARTs. Figure 1 Figure 1. Disclosures Schubert: Gilead: Consultancy. Schmitt: TolerogenixX Ltd: Current Employment; Hexal: Other: Travel grant; Jazz Pharmaceuticals: Other: Travel grant; Therakos/Mallinckrodt: Research Funding. Müller-Tidow: Pfizer: Research Funding; Janssen: Consultancy, Research Funding; Bioline: Research Funding. Dreger: Riemser: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy; BMS: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Bluebird Bio: Consultancy; Roche: Consultancy, Speakers Bureau. Schmitt: MSD: Membership on an entity's Board of Directors or advisory committees; TolerogenixX: Current holder of individual stocks in a privately-held company; Kite Gilead: Other: Travel grants; Bluebird Bio: Other: Travel grants; Novartis: Other: Travel grants, Research Funding; Hexal: Other: Travel grants, Research Funding; Apogenix: Research Funding.

Introduction: We evaluated a predictive formula for CD34+ cell yield from HPC collections at 2 institutions using different mobilization and machine parameters on the COBE® Spectra (Spectra) and Spectra Optia® (Optia) devices. Patients and Methods: Heidelberg: Data were reviewed for all 67 pts who collected autologous HPC from 2/13/14 to 7/11/14. A total of 89 collection events (n) were analyzed (50 male, 39 female). Diagnoses were myeloma (n=64) and non-myeloma (n=25). Age was 17–74 years (median 60). Mobilization was chemotherapy + G-CSF (5 µg/kg SC daily; n=82) or G-CSF (10 µg/kg SC daily, minimum 4 days; n=7) + plerixafor (240 µg/kg SC) added to G-CSF 15 h before collection in poor mobilizers (n=9). Pts were randomly assigned to collect on either Spectra (n=26) or Optia (n=63). Anticoagulant citrate dextrose (ACD) was used at an inlet:anti-coagulant ratio of 15:1 with inlet flow rate of 40–100 mL/min. A central venous line (n=6) or peripheral access (n=83) was used to process 3–4 blood volumes. UAMS: Data were reviewed for all 52 pts who collected HPC from 8/13/13 to 7/10/14. A total of 155 collection events were analyzed (90 male, 65 female). Diagnoses were myeloma (n=127) and non-myeloma (n=28). Age was 24–79 years (median 64). Mobilization used chemotherapy + G-CSF (5–8 mg/kg SC twice daily; n=116) or G-CSF (5–8 mg/kg SC twice daily; n=39) + plerixafor (240 µg/kg SC) added to G-CSF 15 h before leukapheresis in poor mobilizers (n=41). All pts had central venous lines. Spectra pts (n=133) had 5–40 L blood processed using 1,000 mL ACD and 5,000 U heparin for anticoagulation at an inlet:anti-coagulant ratio of 31:1, inlet flow rate of 150 mL/min. Collection flow rate was set at 1.5 mL/min and 10 mL ACD was added to the component at processed volumes of 10 L, 20 L and 30 L. Optia pts (n=22) had 7–23 L blood processed using ACD at a ratio of 12:1 for the first chamber, changing to 25:1 during first chamber collection phase, with a maximum inlet flow rate of 125 mL/min. Heparinized citrate was used as with the Spectra, with 3 mL of ACD without heparin added to the product bag before start of collection, and 1 mL of ACD was added for every chamber processed during the procedure after every 10 L, with an aim to keep the concentration in the product bag 10% by volume. Pts were collected randomly on Optia one day and Spectra another and if platelet count was ≥80 K/mL were given 81 mg aspirin at start of collection. Both institutions: continuous CaCl₂ infusion was used to prevent side effects of citrate for both machines, and CD34+ cells were quantified by flow cytometry using the ISHAGE protocol. Prediction of CD34+ cells collected/L blood processed was calculated using the formula: (peripheral blood CD34+ cells/µL) × (estimated collection efficiency of 30%) / body weight (kg) (Rosenbaum et al. Cytotherapy, 2012;14:461–466). Predicted CD34+ counts/kg were plotted on the x-axis against corresponding observed counts (y-axis) for all collections and the scatter plots assessed for linear relationship between predicted and observed. Linear regression analyses were performed and the linear correlation coefficients (r-values) were calculated; slope and intercepts of the regression lines were evaluated. The same analyses were performed on the following subgroups: combined data for both institutions, data for Spectra and Optia separately by institution, and Spectra and Optia data separately but combining institutions. Results: Regression analyses performed on all collection events categorized by institution demonstrated very strong linear correlations between predicted and observed values [r=0.88 (y=1.64x - 0.10) and 0.92 (y=1.14x + 0.88), Heidelberg and UAMS, respectively]. For data combined for both institutions, strong linear correlation persisted [r=0.91 (y=1.17x + 1.31); Figure]. Data categorized by machine used (Spectra vs. Optia) both within institution and combining institutional data showed consistently strong linear correlation (r-values all >0.84). Conclusions: This is the first report confirming inter-institutional reproducibility of this formula for predicting the minimum number of CD34+ cells that may be expected for a given number of liters of blood processed for an HPC collection. We also demonstrate that inter-institutional differences in mobilization regimens and collection parameters do not affect efficacy of the prediction, nor does machine type used (Spectra vs. Optia). Figure 1 Figure 1. Disclosures Wuchter: Sanofi: Honoraria; ETICHO: Consultancy, Honoraria. Hundemer:Celgene: Research Funding, Speakers Bureau; Genzyme: Research Funding. Goldschmidt:Celgene: Consultancy, Research Funding, Speakers Bureau. Ho:Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.