INTRAVENOUS IMMUNOGLOBULIN THERAPY USE IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA TREATED WITH TISAGENLECLEUCEL IN THE JULIET TRIAL

Abstract

treated with locally produced anti-CD19 CAR T-cells. Eligibility of the pts enrolled reflected a real world setting. Aim: To evaluate the safety, efficacy, and clinical/PET-CT imaging parameters associated with survival outcomes. Methods: Pts with R/R aBCL and adequate organ function were eligible. The approach used autologous T-cells expressing anti-CD19 CAR construct with CD28 co-stimulatory domain. Treatment included lymphodepletion with fludarabine and cyclophosphamide followed by infusion of fresh 1 X 10 CAR T-cells after 9-10 days of culture. Baseline PET-CT scans, which were done within maximum 2 weeks before CAR T-cell treatment, were analyzed for total lesion glycolysis (TLG) and total metabolic tumor volume, using a segmentation algorithm of 41%SUVmax (TMTV41%). Results: Between November 2016 and January 2019, 30 pts with R/R aBCL were included: 25 with diffuse large B cell lymphoma (6 of them were transformed), 3 with primary mediastinal lymphoma and 2 with Burkitt lymphoma. 23 pts were male. Median age was 45 (range 19-66). Median number of prior therapies was 3 (range 2-6). 27 pts (90%) were refractory to their last therapy. 13 (43%) had a prior stem cell transplantation (SCT) (11 – auto, 1 – allo, 1 – auto and allo). The overall response rate was 57% (27% CR). With a median follow-up of 5.1 month (1.2-26.5) median overall and progression free survival (PFS) were 20.7 and 3.7 months, respectively. The estimated PFS at 18 months for the entire cohort was 25%, and 44% among the 17 pts who had an objective response. 11 patients deceased, 9 of them due to disease progression and 2 from transplant related toxicity. No deaths were attributed to CAR T-cell therapy. Cytokine release syndrome occurred in 22 pts (73%), but was severe in only one. 11 pts (37%) experienced neurotoxicity, in 6 (20%) it was grade 3 or 4. Toxicities related to CAR T-cell therapy did not predict survival outcomes. Median baseline TMTV and TLG were 76 (7-1357) and 717 (19-8460), respectively. None of these PET-CT measurements and other baseline patient and disease characteristics, including CRP and stage, predicted OS or PFS. AlloSCT was performed after CAR Tcell therapy in 13/30 patients (43%). Severe acute GVHD and sinusoidal obstruction syndrome were identified in 2/13 patients (15%), each. Conclusion: This prospective analysis of a single center cohort of mostly refractory aBCL pts treated with in-house produced antiCD19 CAR T-cell therapy suggests that long-term responses may be achieved, particularly in pts who had an objective response. None of the clinical and PET-CT parameters that indicate tumor burden predicted long term survival.