A Systematic Review and Meta-Analysis of CD22 Car T-Cells Alone or in Combination with CD19 Car T-Cells

Abstract

Background: Chimeric antigen receptor (CAR) T-cells targeting CD22 may benefit patients with B-cell malignancies, especially those that have failed CD19 CAR T-cells. CAR T-cells co-targeting CD19 and CD22 may prevent relapse due to antigen loss. We conducted a systematic review and meta-analysis evaluating the efficacy and toxicity of CD22-targeting CAR T-cells. \n \nMethods: We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to July 8, 2020 for full-length articles and conference abstracts of clinical trials employing CD22-targetting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL); primary outcome was best complete response (bCR).\xa0 A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. \n \nFindings: Fifty-nine of 601 references were included, representing 14 early phase studies with 339 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 66% [95% CI, 52-79%] in ALL (n= 100), with 73% of patients having received anti-CD19 CART previously. CD19/CD22 CAR T-cells had a bCR rate of 95% [95% CI, 87-99%] in ALL (n= 150) and 51% [95% CI, 38-63%] in NHL (n= 61). The estimated incidence of total and severe (grade ≥3) CRS were 85% [95% CI, 79-91] and 43% [95% CI, 1%-8%]. ICANS and severe ICANS had an estimated incidence of 14% [95% CI, 8-22%] and 1% [95% CI, 0-3%]. \n \nInterpretations: Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL, and CD19/CD22 CAR T-cells have also shown substantial remissions in NHL. Severe CRS or ICANS were rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors between studies limits comparisons. Long-term outcomes are yet to be reported and will reveal whether responses translate into durable long-term remission. \n \nFunding: BioCanRx.Systematic Review Registration: PROSPERO CRD42020193027 \n \nDeclaration of Interest: KAH serves on advisory board for Kite/Gilead, Cellgene/BMS, Novaratis, and receives payments for Jazz Pharmaceutical educational programs. KAH has also received travel support for meetings from BioCanRx. NJF, KA, NK, and HA report no competing interests.