CD19‐DIRECTED CAR T CELL THERAPY (CTL019) FOR RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL AND FOLLICULAR LYMPHOMAS: FOUR YEAR OUTCOMES (2019)

Introduction: Anti-CD19 chimeric antigen receptor-modified T cell therapy (CAR T) is indicated for diffuse large B-cell, high grade B-cell, transformed follicular and primary mediastinal B-cell lymphomas. To date, the longest reported median follow-up is 19 months (mo) for tisagenlecleucel (Schuster et al., Blood 2018) and 24 mo for axicabtagene ciloleucel (Locke et al., Lancet Oncol 2019). We previously reported two-year follow-up for 28 patients (pts) who received CTL019 (Schuster et al., NEJM 2017). We now report our four-year experience with CAR T (CTL019, now tisagenlecleucel). Methods: We enrolled pts with relapsed/refractory CD19+ diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) from February 2014 to September 2017 on a single institution trial of CTL019. Eligible pts had no curative treatment options, prognosis of <2 years survival, and less than complete response to last therapy. Pts underwent leukapheresis, bridging therapy at the investigator's discretion, then lymphodepleting therapy followed by a single dose of 1e8 to 5e8 CTL019 cells. Outcomes were analyzed as of February 25, 2019. Results: Median follow-up is now 49 mos. 49 pts, 24 with DLBCL and 15 with FL, were enrolled. Median age at enrollment was 56 years (range: 25 – 77) and 41% were women. The median number of prior therapies was 5 (range: 2-10). Median ECOG PS was 1 (range: 0-1). 78% had advanced stage lymphoma at enrollment. 38 pts received the protocol-specified dose of CTL019. 46% of DLBCL pts and 71% of FL pts had a complete response (CR). For DLBCL, median progression free survival (PFS) is 5.8 mo (95%CI: 1.6 mo-NE), median overall survival (OS) 22.2 mo (95%CI: 10.9-45.6mo). For FL, median PFS is 32.4 mo (95%CI: 3.5 mo-NE), median OS was not reached (95%CI: 27.2mo-NE). For responding patients with DLBCL or FL, median response duration (RD) was not reached at 49 mo follow-up (DLBCL RD, 95%CI: 3.2 mo-NE; FL RD, 95%CI: 9.5 mo-NE). The patient with the longest follow-up remains in remission from DLBCL (double-hit) at 60 mo after CTL019. Of 21 pts in CR, only 6 received IVIG for recurrent or severe infections and 2 pts developed late myelodysplasia. Four patients relapsed more than 12 months from CTL019 infusion (PFS: 16.3 mo, 26.2 mo, 32.4 mo, 35.2 mo). At the time of these late relapses, CAR T cells persisted by quantitative PCR and there was no loss of CD19 expression by tumor cells. Keywords: diffuse large B-cell lymphoma (DLBCL); follicular lymphoma (FL); T-cells. Disclosures: Chong, E: Consultant Advisory Role: Novartis. Svoboda, J: Consultant Advisory Role: Kite Pharma; Research Funding: Novartis. Nasta, S: Research Funding: Roche, Incyte, Debiopharm, Rafael, Aileron, Takeda/Millennium. Landsburg, D: Consultant Advisory Role: Curis, Celgene; Research Funding: Curis, Takeda, Triphase; Other Remuneration: Seattle Genetics =. Porter, D: Employment Leadership Position: Genentech; Consultant Advisory Role: Novartis, Kite Pharma, Incyte, Glenmark; Stock Ownership: Genentech; Research Funding: Novartis; Other Remuneration: Novartis. Levine, B: Employment Leadership Position: Tmunity Therapeutics; Consultant Advisory Role: CRC Oncology, Cure Genetics, Novartis, Terumo, Avectas, Brammer Bio, Incysus, Vycellix; Other Remuneration: Novartis. June, C: Consultant Advisory Role: Novartis, Immune Design, Viracta, Carisma; Stock Ownership: Tmunity Therapeutics; Research Funding: Novartis; Other Remuneration: Novartis. Schuster, S: Consultant Advisory Role: Pfizer, Nordic Nanovector, Celgene, Gilead, Merck, Novartis, Pharmacyclics, Loxo Oncology, Acerta, AstraZeneca; Research Funding: Acerta, Celgene, Genentech, Gilead, Merck, Novartis, Pharmacyclics; Other Remuneration: Novartis.