Comparison of Tisagenlecleucel With Historical Treatments For Relapsed or Refractory Diffuse Large B-cell Lymphoma: a Retrospective Study Using External Comparator From the Korean Lymphoma Registry Data

Background: Tisagenlecleucel (Tisa-cel) is an autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Yet, there is a paucity of data on head-to-head comparison between tisa-cel vs historical treatments in improving patient survival.

Objectives: To explore the overall survival (OS) associated with tisa-cel in r/r DLBCL patients

Methods: We indirectly compared the effectiveness of tisa-cel, using data from the JULIET single arm trial (Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients), vs historical treatments assessed in the SMC-LCS (Samsung Medical Center-Lymphoma Cohort Study); published aggregate data from JULIET and patient-level data from SMC-LCS were used. DLBCL Patients in the SMC-LCS, enrolled from September 2008 to February 2017, were eligible for inclusion if they met the eligibility criteria of JULIET. OS in eligible patients, defined as the time interval from index treatment to death or the date of last follow-up visit, was compared with tisa-cel (full analysis set) population in JULIET. Propensity score weighting using matching-adjusted indirect comparison approach was used to compare OS, adjusting for the baseline characteristics. The adjusted hazard ratio (aHR) with corresponding 95% confidence interval (CI), comparing tisa-cel vs historical treatments, were estimated using Cox proportional hazards model.

Results: Of 2321 patients in SMC-LCS, 244 (10.5%) were with r/r DLBCL. After applying eligibility criteria, 53 were included in the historical treatment cohort. Median age at enrollment was 56 vs 55 years, proportion with refractory DLBCL 55.0% vs 26.4%, and median OS 11.7 vs 5.4 months for tisa-cel arm vs. historical treatment cohort, respectively. By the end of study period, all-cause mortality rate was 48.6% (54/111) for tisa-cel arm vs. 88.7% (47/53) for historical treatment cohort, corresponding to aHR of 0.59 (95% CI, 0.40-0.85).

Conclusions: Tisa-cel was superior to historical treatments in prolonging OS in patients with r/r DLBCL. This study adds on the existing evidence by indirectly comparing between the data from published single arm trial and patient-level registry data to show tisa-cel is expected to improve OS in patients with r/r DLBCL among Korean population.