ASH 2020 | Ibrutinib therapy prior to tisa-cel in R/R DLBCL

Frederick Locke, MD, Moffitt Cancer Center, Tampa, FL, discusses the results of a Phase Ib safety trial (NCT03876028) of tisagenlecleucel (tisa-cel) in combination with ibrutinib, a BTK inhibitor, in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients. Preclinical suggestions of improved T-cell manufacturing and antitumor efficacy with prior ibrutinib therapy, as well as the potential for mitigation of CAR T-cell-related toxicities through inhibition of BTK-mediated pro-inflammatory macrophage polarization, provided the rationale for this trial. Two patient arms were enrolled, providing ibrutinib before and after leukapheresis, respectively. The initial findings in 10 patients show promising response rates and safety data that supports ibrutinib use. The median viability of collected material was higher in those treated prior to leukapheresis, as well as having a higher proportion of stem-cell like central memory cells and a higher median final CAR-T dose when compared to patients treated after. This suggests ibrutinib may be able to improve CAR T-cell manufacturing. Studies are ongoing. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.