Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results

• Type of Material: Article
• Authors: Ulrich Jaeger, Medical University of Vienna; Nina Worel, Medical University of Vienna; Joseph P McGuirk, The University of Kansas Health System; Peter A Riedell, University of Chicago; Isabelle Fleury, Maisonneuve-Rosement Hospital; Yan Du, Novartis Institutes for Biomedical Research; Xia Han, Novartis Pharmaceuticals Corporation; David Pearson, Novartis Pharmaceuticals Corporation; Santiago Redondo, Novartis Farmaceut SA; Edmund Waller, Emory University
• Language: English
• Date: 2023-05-26
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2022007779
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 7
• Issue: 11
• Start Page: 2283
• End Page: 2286
• Keywords: Science & Technology; BLOCKADE; T-CELLS; Life Sciences & Biomedicine; Hematology
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Tisagenlecleucel demonstrated high response rates and a manageable safety profile in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL) in the JULIET trial. However, lack of response and chimeric antigen receptor (CAR) T-cell exhaustion were observed in patients with programmed cell death protein 1 (PD-1) overexpression. Hence, pembrolizumab, a PD-1 inhibitor, was hypothesized to improve efficacy and cellular expansion of CAR T-cells in vivo. Here, we report the final analysis of the PORTIA trial in adult patients with r/r DLBCL who had ≥2 prior lines of therapy and had an Eastern Cooperative Oncology Group performance status of .1. Patients received 1 tisagenlecleucel infusion on day 1. Pembrolizumab (200 mg) was given every 21 days, for up to 6 doses. Three cohorts initiated pembrolizumab on days 15 (n = 4), 8 (n = 4), or .1 (n = 4). Safety, efficacy, cellular kinetics, and biomarker analyses were included. Tisagenlecleucel plus pembrolizumab was feasible and showed a manageable safety profile, without dose-limiting toxicities. Emerging efficacy with tisagenlecleucel was observed when pembrolizumab was given the day before tisagenlecleucel; however, the limited patient sample and short follow-up do not allow for definitive conclusions. Adding pembrolizumab to tisagenlecleucel did not augment the cellular expansion of tisagenlecleucel but delayed peak expansion if given the day before tisagenlecleucel (NCT03630159).