New CAR Designs: Highlights From SOHO 2020

Abstract

P atients with acute lymphocytic leukemia (ALL) or diffuse large B-cell lymphoma (DLBCL) can look forward to tremendous benefits with the approval of chimeric antigen receptor (CAR) T-cell therapy. Often touted are the exceptional response rates in heavily pretreated patients along with meaningful durability of response and ultimately progressionfree survival that were found in the ZUMA-1 and JULIET studies for axicabtagene ciloleucel (axicel, Yescarta) and tisagenlecleucel (tisa-cel, Kymriah), respectively (Neelapu et al., 2017; Schuster et al., 2019). However, these pivotal studies also illustrate that patients achieving less than a complete response (CR) are not enjoying the same benefits compared with those meeting the criteria for CR after CAR T-cell therapy. Additionally, providers must be aware of the potential emergence of CD19 escape variants that have been described in patients relapsing after CAR T-cell therapy (Xu et al., 2019). These disparate outcomes based on depth of response and challenges with CD19-negative relapses demonstrate an unmet need that have investigators eager to build a better CAR.