S1600 REAL‐WORLD RESULTS ON CD19 CAR T‐CELL FOR 60 FRENCH PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA INCLUDED IN A TEMPORARY AUTHORIZATION FOR USE (ATU) PROGRAM (2019)

Background: Autologous anti‐CD19 chimeric antigen receptor (CD19 CAR) T‐cell therapy demonstrated significant clinical benefit and a manageable safety profile for patients with relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL), with 6‐month ORR at 41–47% and CR at 32–41% in the 3 pivotal clinical trials (ZUMA1, TRANSCEND, JUNO), leading to a rapid approval in third line R/R DLBCL in Europe and USA. Since April 2018 in France, a cohort patient program (called ATU in France) allowed to use the CD19 CAR T‐cells, Axicabtagene and Tisagenlecleucel, for patients with DLBCL, primary mediastinal B‐cell lymphomas (PMBL) and transformed FL (tFL), recurrent or refractory after &gt; 2 systemic therapy lines; CNS excluded. Aims: Here we describe the organization in the 5 authorized centres (APHP, Hôpital Saint‐Louis‐Paris, CHU Montpellier, CHU Nantes, CHU Lyon, CHU Lille). Methods: We performed a retrospective analysis of the patients treated with Axicabtagene or Tisagenlecleucel between April 2018 and Feb 2019. The eligibility criteria were confirmed based on age, comorbidities, LVEF &gt; 45%, no pericarditis or cardiogram abnormality, clearance &gt; 60 mL/min, ALT/AST ≤ 2.5 N, total bilirubin &lt; 1.5 mg/dL, no pleural effusion, SpO2 &gt; 92% without oxygen, lymphocytes ≥ 100/μL, no rapid progressive disease (compressive mass, PS &gt; 2 or rapid increase of LDH), no active neurological disease, no auto‐immune disease. The final decision was validated by a local multidisciplinary tumor board. Results: A total of 60 patients have been selected for a treatment with Yescarta (30) or Kymriah (30). 73% of the patients were referred. Median age was 52 (range 18 ‐77). 11 (18%) pts were over 65 years old. 67% were male. By histology, patients presented with DLBCL (n = 42), PMBL (n = 8), trFL (n = 9), and transformed marginal zone lymphoma (n = 1). 68% were primary refractory defined as progressive or stable disease as the best response to the most recent chemotherapy regimen or disease progression or relapse within 12 months after autologous stem cell transplantation (ASCT). Median number of prior lines was 3 (range 2 to 9) and 18 (30%) pts had a prior ASCT. Only one leukapheresis was necessary, except for 4 patients who required 2–4 leukapheresis. At time of analysis, 45 patients have been reinfused. 5 patients died before reinfusion, 3 because progressive disease and 2 because of infections. The median time duration between the ATU validation and receipt of the CD19 CAR T‐cells was 47.5 days (range 30–190 days). During this time, all patients except 4 (93%) received a bridging therapy including dexamethasone alone (1), rituximab (3), brentuximab vedotin (1), pembrolizumab (2), revlimid or rituximab‐revlimid (2), or immunochimiotherapy (R‐IFO‐VP16, R‐MIV, R‐PIV, BV‐bendamustine, GVD‐BV, R‐GEMOX /Vinblastine+steroids, BV‐ICE, R‐BV‐DHAC, vinblastine+steroids, R‐MTX, R‐cyclophosphamide)(34), or radiation therapy (1). The median time between the receipt of the cells and their infusion was 6 days (range 1 to 20 days). Summary/Conclusion: The time elapsed between ATU validation and CAR T‐cell reception remains substantial and a bridging therapy was necessary for almost all patients. The LYSA group and the CALYM institute ( www.calym.org ) are organizing a national registration program for these patients with clinical and biological data collection.