Introduction: The autologous anti-CD19 chimeric antigen receptor (CD19 CAR) T-cells demonstrated significant clinical benefits and a manageable safety profile in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), with an ORR of 52-83% and CR of 40-58% in the 3 pivotal clinical trials (ZUMA-1, TRANSCEND-NHL-001, JULIET), leading to a rapid approval in third line R/R DLBCL in Europe and in USA. The CD19 CAR T-cells Axicabtagene and Tisagenlecleucel have been approved in France since June 2018 for patients with DLBCL, primary mediastinal B-cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after > 2 systemic therapy lines. However, all patients are not deemed eligible for such therapy. Here we describe the characteristics of the non-eligible patients and the causes of non-eligibility for CD19 CAR T-cells at our center. Methods: We performed a retrospective analysis of all patients for whom our center was contacted for potential eligibility to CD19 CAR T-cells. Upon each request, a screening form was completed by the referring hospital to validate the indication (DLBCL, PMBL or tFL; recurrent or refractory to > 2 systemic therapy lines) and the absence of contra-indications (CNS involvement (MRI mandatory), active infection). The patient was then evaluated in our hospital to check the predetermined eligibility criteria: age, comorbidities, LVEF > 45%, no pericarditis or cardiogram abnormality, creatinine clearance > 60 mL/min, ALT/AST < 2.5 N, total bilirubin < 1.5 mg/dL, no pleural effusion, SpO2 > 92% without oxygen, lymphocytes > 100/µL, no rapid progressive disease (compressive mass, PS > 2 or rapid increase of LDH), or no active neurological/auto-immune disease. In case of severe comorbidities or age> 70, patient's frailty index was assessed by an ICU physician. Eligibility was then finally validated by our local board through a careful case-by-case analysis. Results: Between June 2018 and July 31, 2019, 221 requests were analyzed. Evaluation is still ongoing for 6 patients (3%). 80/215 patients (37%) were deemed eligible for CAR T-cells, 58 patients (27%) were excluded before any visit at the expert hospital because of histology other than DLBCL, PMBL and tFL (n=30: non-transformed FL 9, transformed SLL/CLL 7, transformed Waldenström 3, transformed MZL 3, MZL 2, primary CNS lymphoma 2, SLL/CLL 1, HL 1, lymphoblastic lymphoma 1, CD19- 1), < 2 previous lines (n=7), CNS involvement (n=7), administrative reason (n=14). The remaining 77 patients (36%) were deemed non-eligible for CAR T-cells after the first visit. Median age was 59 years (range 18-86, 41% ≥ 65 years), 68% were male. There were 62, 4 and 2 patients with DLBCL, PMBL and tFL, respectively. Median number of prior lines was 3 (range 2-11, 43% > 3 lines), 86% of patients presented with a primary refractory disease. Nine patients were with a refractory disease despite stem cell transplantation (SCT, 5 autologous, 3 allogeneic and 1 both). Considering these 77 patients, 12 (16%) had 2 concomitant causes of non-eligibility. Overall, the two main causes of non-eligibility were rapid disease progression (n=49) and major frailty (n=23), including 10 patients with 11 severe organ dysfunctions [5 cardiac, 3 kidney, 1 liver, 1 respiratory and 1 heavy engine handicap]. Replicative viral infections (n=4) constituted also an important cause of frailty: HIV (1), HBV (2), HBV + HCV (1). Two patients had a solid organ transplantation requiring immunosuppressive drugs. Advanced neurological diseases (n=4) included: extrapyramidal syndrome (3), advanced multiple sclerosis (1). Active autoimmune diseases were a cause of frailty for 2 patients: thyroiditis (1), periodic fever (1). In one patient, the screening evaluation showed a concomitant malignancy. Other causes of non-eligibility were found in 17 patients: complete remission after the salvage therapy (n=7), age > 80 (n=4), severe thrombocytopenia < 20 G/L (n=2), no slot available (n=1), patient refusal (n=3). Outcomes of the non-eligible patients (alternative treatments, survival) will be presented at the meeting. Conclusion: In this pioneering experience, 37% of patients in whom a CAR T-cell request is made are ultimately deemed eligible for the therapy. Other patients are either rapidly excluded based on lack of CAR T-cells indications (27%), or deemed non-eligible because of failure to control the disease / major frailty (36%). Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Casasnovas:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Merck Sharp and Dohme: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cartron:Roche, Celgene: Consultancy; Sanofi, Gilead, Janssen, Roche, Celgene: Honoraria. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Gyan:Pfizer: Honoraria. Haioun:novartis: Honoraria; celgene: Honoraria; roche: Consultancy; celgene: Consultancy; gilead: Consultancy; takeda: Consultancy; janssen cilag: Consultancy; amgen: Honoraria; servier: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Novartis: Honoraria.

Background: MPSIH is a lysosomal storage disease caused by a-L-iduronidase (IDUA) deficiency that is associated with progressive multisystem morbidity including neurodevelopmental deterioration and severe orthopedic manifestations, leading to death in early childhood. Current

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