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We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19+ malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4–5 × 106 ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin’s lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%–67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%–88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583 .

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We evaluated the administration of ARI-0001 cells (chimeric antigen receptor T cells targeting CD19) in adult and pediatric patients with relapsed/refractory CD19(+) malignancies. Patients received cyclophosphamide and fludarabine followed by ARI-0001 cells at a dose of 0.4–5 × 10(6) ARI-0001 cells/kg, initially as a single dose and later split into 3 fractions (10%, 30%, and 60%) with full administration depending on the absence of cytokine release syndrome (CRS). 58 patients were included, of which 47 received therapy: 38 with acute lymphoblastic leukemia (ALL), 8 with non-Hodgkin’s lymphoma, and 1 with chronic lymphocytic leukemia. In patients with ALL, grade ≥3 CRS was observed in 13.2% (26.7% before versus 4.3% after the amendment), grade ≥3 neurotoxicity was observed in 2.6%, and the procedure-related mortality was 7.9% at day +100, with no procedure-related deaths after the amendment. The measurable residual disease-negative complete response rate was 71.1% at day +100. Progression-free survival was 47% (95% IC 27%–67%) at 1 year: 51.3% before versus 39.5% after the amendment. Overall survival was 68.6% (95% IC 49.2%–88%) at 1 year. In conclusion, the administration of ARI-0001 cells provided safety and efficacy results that are comparable with other academic or commercially available products. This trial was registered as ClinicalTrials.gov: NCT03144583.

Objective: To calculate, for the first time, the direct and social costs of transfusion-related adverse events in order to include them in the National Healthcare System's budget, calculation and studies. In Spain more than 1,500 patients yearly are diagnosed with such adverse events. Method: Blood transfusion-related adverse events recorded yearly in Spanish haemovigilance reports were studied retrospectively (2010-2015). The adverse events were coded according to the classification of Diagnosis-Related Groups. The direct healthcare costs were obtained from public information sources. The productivity loss (social cost) associated with adverse events was calculated using the human capital and hedonic salary methodologies. Results: In 2015, 1,588 patients had adverse events that resulted in direct health care costs (4,568,914€) and social costs due to hospitalization (200,724€). Three adverse reactions resulted in patient death (at a social cost of 1,364,805€). In total, the cost of blood transfusion-related adverse events was 6,134,443€ in Spain. For the period 2010-2015: the trends show a reduction in the total amount of transfusions (2 vs. 1.91 M€; -4.4%). The number of adverse events increased (822 vs. 1,588; +93%), as well as their related direct healthcare cost (3.22 vs. 4.57M€; +42%) and the social cost of hospitalization (110 vs 200M€; +83%). Mortality costs decreased (2.65 vs. 1.36M€; -48%). Discussion: This is the first time that the costs of post-transfusion adverse events have been calculated in Spain. These new figures and trends should be taken into consideration in any cost-effectiveness study or trial of new surgical techniques or sanitary policies that influence blood transfusion activities. Resumen: Objetivo: Calcular por primera vez los costes económicos y sociales relacionados con las reacciones adversas postransfusionales para actualizar estudios e incluirlos en los presupuestos del Sistema Nacional de Salud. En España, anualmente, más de 1500 pacientes sufren dichas reacciones adversas. Método: Se estudiaron retrospectivamente (periodo 2010-2015) las reacciones adversas a la transfusión recopiladas anualmente en los informes nacionales de hemovigilancia. Dichas reacciones se codificaron mediante clasificación de Grupos Relacionados con el Diagnóstico. Los costes directos sanitarios se obtuvieron de fuentes públicas de información. La pérdida en productividad (coste social) asociada a las reacciones adversas se contabilizó utilizando los métodos del capital humano y salarios hedónicos, respectivamente. Resultados: En el año 2015, en España, 1588 pacientes tuvieron reacciones adversas que derivaron en costes sanitarios (4.568.914 €) y costes sociales debido a hospitalización (200.724 €). Tres reacciones adversas resultaron en muerte del paciente (1.364.805 €). Como suma, el coste total de las reacciones adversas a la transfusión fue de 6.134.443 €. Periodo 2010-2015: la tendencia refleja una reducción en el número total de transfusiones (2 vs. 1,91 M€; -4,4%), un incremento en el número de reacciones adversas (822 vs. 1.588; +93%), en costes sanitarios (3,22 vs. 4,57M€; +42%) y en costes sociales (110 vs. 200M€; +83%), y un descenso en costes de mortalidad (2,65 vs. 1,36M€; -48%). Discusión: Por primera vez se han calculado en España los costes de las reacciones adversas a la transfusión. Los nuevos datos y tendencias deberían ser considerados en estudios de coste-eficiencia sobre técnicas quirúrgicas o políticas sanitarias con repercusión en actividades de transfusión sanguínea. Keywords: Adverse effects, Blood transfusion, Health care costs, Costs and cost analysis, Trends, Palabras clave: Reacciones adversas, Transfusión sanguínea, Costes de la atención en salud, Costes y análisis de costes, Tendencias

Background: ARI0002h is an academic lentiviral autologous second-generation CAR T-cell product with a 4-1BB co-stimulatory domain and a humanized single chain variable fragment targeting BCMA. In pre-clinical studies, ARI0002h has demonstrated potent in vitro and in vivo activity. Here, we report the first safety and efficacy results of the CARTBCMA-HCB-01 multicenter clinical trial for patients with relapsed/refractory multiple myeloma (RRMM) (NCT04309981) who received ARI0002h in 5 Spanish centers. Methods: Patients (pts) aged 18-75 years old with RRMM were eligible for this study if they had measurable disease, as assessed by M-protein or serum free light chain levels, received ≥2 prior regimens, including a proteasome inhibitor, an immunomodulatory drug (lenalidomide or pomalidomide) and an anti-CD38 antibody, and were refractory to the last line of treatment. Bridging therapy was allowed after apheresis. Cyclophosphamide (300 mg/m 2) and fludarabine (30 mg/m 2) on days -6 to -3 were used as lymphodepletion regimen. The targeted dose was 3x10 6/kg CAR+cells (range 1.2-3x10 6) and was administered in a fractionated manner (10%/30%/60%), with at least 24h between infusions. A second dose of 3x10 6 CAR+ cells/kg was planned at least 4 months after the first dose in pts who had any response and had not presented MM progression or serious complications after the first administration, with or without repeated lymphodepletion depending on the persistence of CAR-T cells. Primary objectives were overall response rate (ORR; at less partial response -PR-) within 3 months of the first infusion and rate of cytokine release syndrome (CRS) and/or neurological toxicity in the first 30 days. Response was assessed as per IMWG criteria and bone marrow minimal residual disease (MRD) was analyzed by next-generation flow. Adverse events (AEs) were graded using CTCAE v5.0. CRS and neurotoxicity were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria. Results: As of July 19 th, 35 pts (median age 61 years) with RRMM were included in the trial. Four pts could not receive ARI-0002h due to MM progression before apheresis (2 pts) or treatment (2 pts) and one pt died of a fungal infection. Therefore, 30 pts received ARI0002h cells (modified intention-to-treat population), of which 47% received bridging therapy. The main characteristics of these pts and previous treatments are described in Table 1. Median CAR-T cell production time was 11 days (range 9-14) with a 100% manufacture success. Median follow-up after ARI0002h administration for surviving pts was 8 months (range 2-12). The ORR of 27 evaluable pts at 3 months was 96%, with a stringent complete remission (sCR) rate of 44.4% (Table 1) and very good partial response (VGPR) observed in 18.6% of pts. Median time to first response was one month. All pts achieved at least a PR and only one patient progressed after 4 months exclusively with extramedullary disease. Of 25 MRD-evaluable pts at day +100, 92% were MRD-negative. Median progression-free survival (PFS) and overall survival (OS) were not reached and the 6-month PFS and OS rates were 92.1% (Figure 1) and 95.8%, respectively. AEs reported in >70% of pts were CRS (87%; grade [gr] 3/4 0%; gr 1 73%), neutropenia (97%; gr 3/4 100%), anemia (85%; gr 3/4 43%), and thrombocytopenia (79%; gr 3/4 70%). Median duration of CRS was 4 days (range 1-12). No CAR-T cell-related neurotoxicity cases were reported. Tocilizumab and corticosteroids were administered in 76% (mainly for persistent grade 1 CRS) and 12% of pts, respectively. One death occurred due to unrelated causes (cranial traumatism). ARI0002h cells demonstrated peak expansion on day 14 (range 7-100 days). Among the pts with 3 and 6 months follow-up, 54% and 24% had measurable CAR+ T cells in peripheral blood, respectively. 22 out of 27 eligible pts (81%) have already received the second dose (range 1.2-3x10 6 CAR+ cells/kg). Median time after first infusion was 4 months; 36% received a second lymphodepletion. No relevant toxicities after second infusions were reported. Responses deepened over time and at 6 months, 5 pts who had reached PR achieved VGPR and one improved from VGPR to sCR. Conclusion: ARI0002h is the first European academic CAR T-cell for RRMM that has demonstrated excellent feasibility in a clinical trial, with deep and durable responses and a favorable safety profile, including the absence of neurotoxicity. Figure 1 Figure 1. Disclosures Fernandez de Larrea: Takeda: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; GSK: Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Honoraria, Research Funding. Gonzalez-Calle: BMS, Janssen, Amgen: Honoraria. Cabañas: Janssen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Honoraria. Rodriguez-Otero: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Clínica Universidad de Navarra: Current Employment; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Regeneron: Honoraria. Reguera: BMS-Celgene, Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen, Kite/Gilead, Novartis: Speakers Bureau. Corral: Novartis: Consultancy; Gileqd: Honoraria; Gilead: Consultancy. Paiva: Bristol-Myers Squibb-Celgene, Janssen, and Sanofi: Consultancy; Adaptive, Amgen, Bristol-Myers Squibb-Celgene, Janssen, Kite Pharma, Sanofi and Takeda: Honoraria; Celgene, EngMab, Roche, Sanofi, Takeda: Research Funding. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Perez-Simon: JANSSEN, TAKEDA, PFIZER, JAZZ, BMS, AMGEN, GILEAD: Other: honorarium or budget for research projects and/or participation in advisory boards and / or learning activities and / or conferences. Prósper: BMS-Celgene: Honoraria, Research Funding; Janssen: Honoraria; Oryzon: Honoraria. Moraleda: Pfizer: Other: Educational Grants, Research Funding; Sanofi: Other: Educational Grants, Research Funding; MSD: Other: Educational Grants, Research Funding; ROCHE: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Takeda: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Sandoz: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Gilead: Consultancy, Honoraria, Other: Educational Grants, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Educational Grants, Research Funding; NovoNordisk: Other: Educational Grants, Research Funding; Janssen: Other: Educational Grants, Research Funding; Celgene: Other: Educational Grants, Research Funding; Amgen: Other: Educational Grants, Research Funding. Mateos: Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Bluebird bio: Honoraria; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria; Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background: Two million transfusions are performed in Spain every year. These come at a high economic price for the health system, increasing the morbidity and mortality rates. The way of obtaining the hemoglobin concentration value is via invasive and intermittent methods, the results of which take time to obtain. The drawbacks of this method mean that some transfusions are unnecessary. New continuous noninvasive hemoglobin measurement technology can save unnecessary transfusions. Methods: A prospective study was carried out with a historical control of two homogeneous groups. The control group used the traditional hemoglobin measurement methodology. The experimental group used the new continuous hemoglobin measurement technology. The difference was analyzed by comparing the transfused units of the groups. The economic savings was calculated by multiplying the cost of a transfusion by the difference in units, taking into account measurement costs. Results: The percentage of patients needing a transfusion decreased by 7.4%, and the number of transfused units per patient by 12.56%. Economic savings per patient were €20.59. At the national level, savings were estimated to be 13,500 transfusions (€1.736 million). Conclusions: Constant monitoring of the hemoglobin level significantly reduces the need for blood transfusions. By using this new measurement technology, health care facilities can significantly reduce costs and improve care quality.

Background Autologous tumour lysate dendritic cell vaccine (ADC) has T-cell stimulatory capacity and, therefore, potential antitumour activity. We designed a phase II randomised trial of ADC + best supportive care (BSC) (experimental arm [EA]) compared with BSC (control arm [CA]), in pre-treated metastatic colorectal cancer (mCRC) patients. Patients and methods Patients with progressive mCRC, at least to two chemotherapy regimens and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2, were randomised to EA versus CA. Stratification criteria: ECOG PS (0–1 versus 2) and lactate dehydrogenase ( ULN). EA was administered subcutaneously till progressive disease. Primary end-point was progression-free survival (PFS) at 4 months. Results Fifty-two patients were included (28 EA/24 CA). An interim analysis recommended early termination for futility. No objective radiological response was observed in EA. Median PFS in EA was 2.7 months (95% confidence interval [CI], 2.3–3.2 months) versus 2.3 months (95% CI, 2.1–2.5 months) in CA (p = 0.628). Median overall survival (OS) was 6.2 months (95% CI, 4.4–7.9 months) in EA versus 4.7 months (95% CI, 2.3–7 months) in CA (p = 0.41). No ADC-related adverse events were reported. Immunization induces tumour-specific T-cell response in 21 of 25 (84%) patients. Responder patients have an OS of 7.3 months (95% CI, 5.2–9.4 months) versus 3.8 months (95% CI, 0.6–6.9 months) in non-responders; p = 0.026). Conclusion Our randomised clinical trial comparing ADC + BSC versus BSC in mCRC demonstrates that ADC generates a tumour-specific immune response but not benefit on PFS and OS. Our results do not support the use of ADC alone, in a phase III trial.

Chronic myelomonocytic leukemia (CMML) has recently been associated with a high incidence of diverse mutations in genes such as TET2 or EZH2 that are implicated in epigenetic mechanisms. We have performed genome-wide DNA methylation arrays and mutational analysis of TET2, IDH1, IDH2, EZH2 and JAK2 in a group of 24 patients with CMML. 249 genes were differentially methylated between CMML patients and controls. Using Ingenuity pathway analysis, we identified enrichment in a gene network centered around PLC, JNK and ERK suggesting that these pathways, whose deregulation has beenrecently described in CMML, are affected by epigenetic mechanisms. Mutations of TET2, JAK2 and EZH2 were found in 15 patients (65%), 4 patients (17%) and 1 patient (4%) respectively while no mutations in the IDH1 and IDH2 genes were identified. Interestingly, patients with wild type TET2 clustered separately from patients with TET2 mutations, showed a higher degree of hypermethylation and were associated with higher risk karyotypes. Our results demonstrate the presence of aberrant DNA methylation in CMML and identifies TET2 mutant CMML as a biologically distinct disease subtype with a different epigenetic profile.

3048 Background: No treatments are available for patients (pts) with metastatic colorectal cancer (mCRC) that progresses after all approved therapies. Autologous tumor lysate dendritic cell vaccine...