A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells

Abstract

Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42020193027.

Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis

“…Inversely to the efficacy evaluations, the safety analysis of CRS showed that the combination of anti-CD19/22 CAR T-cell therapy resulted in the least CRS event, which aligned with a previous meta-analysis [ 52 ]. A retrospective study comparing the severe CRS of the single anti-CD19 and the combination of anti-CD19/22 discovered that significantly more patients developed severe CRS in the anti-CD19 group [ 60 ].…”

“…However, our analysis revealed that this approach was inferior compared to the anti-CD19 or anti-CD22 groups in achieving MRD-CR. Conversely, another meta-analysis discovered a notably higher CR rate when using anti-CD19/CD22 CAR T-cell therapy in comparison to the use of single-target CD22 CAR T-cells [ 52 ]. Nevertheless, it is still early to state the conclusion regarding the performance of anti-CD19/CD22 due to the limited number of studies.…”

“…in 2020 and the CMA by Fergusson et al. in 2023, which described the efficacy and safety of CAR T-cells targeting CD22 and CD19/22 [ 48 , 52 ]. Here, we provided a thorough analysis of the efficacy and safety of CAR T-cell therapy in r/r B-ALL by displaying the subgroup analyses from individual anti-CD19, anti-CD22, and the bispecific antiCD19/CD22 targets.…”

CAR T-Cells in Acute Lymphoblastic Leukemia: Current Status and Future Prospects

“…The incidences of total and severe CRS were 87% and 6%, respectively. The incidences of ICANS and severe ICANS were 16% and 3%, respectively [97]. 50% hypotension 42% anemia 33% grade 3 CRS 21%, 25%, 27%, and 11% neurological events depending on the dose [114] ALL: acute lymphoblastic leukemia; CR: complete remission; Cri: complete remission with incomplete count recovery; CRS: cytokine release syndrome; ICANS: immune effector cell-associated neurotoxicity syndrome; NHL: non-Hodgkin lymphoma; Nr: not reported; OS: overall survival; R/R: relapsed/refractory.…”

Novel and multiple targets for chimeric antigen receptor-based therapies in lymphoma

“…Currently, various CD22-CAR T have entered phase 1 and/or 2 clinical trials, but no phase 3. In a meta-analysis with a data cutoff in March 2022, a total of seven CD22-CAR T clinical trials with 149 patients had primary efficacy data, but only two enrolled patients with lymphoma ( 33 ). A single center phase 1/1b study at Stanford University (NCT04088890) is one of the first trials using autologous CD22-CAR T to treat R/R LBCL ( 34 , 35 ).…”