Tisagenlecleucel in the treatment of aggressive large B-cell lymphoma: A review of literature.

Abstract

e19563 Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for refractory diffuse large B-cell lymphoma(DLBCL) in May 2018. However, a recently concluded phase 3 international trial showed that Tisagenlecleucel was not superior to standard salvage therapy with aggressive lymphoma that was refractory to or progressing within 12 months after first-line treatment. Also, recently the availability of long-term outcomes from earlier trials makes it an excellent time to evaluate the Sustained response(SR) and Adverse effects associated with it. Methods: A comprehensive literature search was done of Pubmed, Embase, and Cochrane. Results: We included three trials which included two multicenter trials and one case series. Schuster et al. in their single-center case series demonstrated that Tisagenlecleucel infusion in patients with refractory diffuse large B-cell lymphoma on median follow-up at 28.6 months showed Complete remission(CR): 43%; 95% CI(18-71) Sustained remission(SR): 86%; 95% CI(13 to 98), Severe cytokine-release syndrome(CRS): 18%. On further median follow-up at 60.7 months showed a CR: 46%, overall response rate(ORR): 58%, Progression-free survival(PFS): 31% (95% CI:14-51). Good recovery in humoral and cellular response. The limitation of the trial was a relatively small number of enrolled patients. JULIET trial, a more extensive multicenter phase 2 trial involving 93 patients, demonstrated that Tisagenlecleucel infusion in patients with refractory diffuse large B-cell lymphoma on 14 months median follow-up showed an ORR: 52% (95% CI, 41 to 62), CR: 40%, Partial response(PR): 12%. On further median follow-up at 40.3 months showed CR: 39%, ORR: 53·0% (95% CI 43·5–62·4). Grade 3-4 CRS: 23%. BELINDA Trial also an extensive multicenter phase 3 trial involving 322 patients which involved patients with aggressive B cell lymphoma that was refractory to or progressing within 12 months after first-line therapy showed infusion of Tisagenlecleucel with optional bridging treatment or salvage chemotherapy and autologous HSCT Showed similar Medial event-free survival(MEFS) at three months for both groups. Progression at six weeks was 25.9% in Tisagenlecleucel vs. 13.8% in the control group. Conclusions: Tisagenlecleucel infusion is shown to have a high rate of durable response in relapsed or refractory diffuse large B-cell lymphoma in adults. Long-term follow-up showing satisfactory ORR with good recovery in cellular and humoral function. However, infusion of Tisagenlecleucel with optional bridging therapy or salvage chemotherapy and autologous HSCT inpatient with aggressive B cell lymphoma that was refractory to or progressing within 12 months after first-line therapy showed Tisagenlecleucel is not superior to standard salvage therapy needing additional studies to evaluate the benefits when used as a second-line agent.