Efficacy and safety of CART22-65s in children and adults with relapsed B-ALL: Parallel phase I studies

The prognosis of post-CAR CD19-negative relapsed B-ALL remains poor, with a median OS of 6–10 months from relapse.¹ This highlights an unmet need for the development of novel therapeutic agents for the treatment of R/R B-ALL. CAR T-cell directed against CD22, a B-cell-specific surface molecule, has shown high clinical activity in early clinical trials. Results from two parallel phase I studies (CHOP, NCT02650414; Penn, NCT03620058) evaluating the efficacy and safety of novel agent CART22-65s in children and adults with R/R B-ALL post CD19-directed therapy were published by Myers et al. in the Journal for ImmunoTherapy of Cancer.¹

The study included data from children and adult patients with B-ALL (N = 19: pediatric cohort n = 17, and adult cohort n = 2) at CHOP or Penn who received CART22-65s between November 2018 and January 2022. The primary endpoint was safety, and secondary endpoints included ORR (defined as the rate of CR or CRi at Day 28 post infusion), MRD-negative rate, EFS, RFS, OS, and engraftment.

Key learnings 

Grade 1 or 2 CRS and neurological toxicities were experienced by 88% and 24% of patients, respectively. Only one case each of Grade 3 CRS/neurotoxicity and high-grade immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome occurred, both in the retreatment setting.

Among patients who received CART22-65s retreatment (n = 2), one patient developed Grade 3 CRS on Day +16 and Grade 3 encephalopathy and areflexic flaccid paralysis on Day +19. The CRS was resolved, but the patient died of PD at Day +31, prior to resolution of neurotoxicity.

At Day 28 post infusion the ORR was 74%, of which 79% of patients were MRD-negative by MFC. Five of 12 patients with the best response of MRD-negative proceeded to consolidation HSCT; two patients remain in CR. 

The median EFS, RFS, and OS were 4.7 months, 5.3 months, and 12.2 months, while the estimated 12-month EFS, RFS, and OS rates were 28.3%, 38.4%, and 52.6%, respectively.

In vivo cellular kinetic data showed robust CART22-65s proliferation by qPCR peaking at a median of 20 days post infusion. CART22-65s cell persistence was observed for up to 42 months in a pediatric patient who remains in durable remission without HSCT.

CART22-65s demonstrated low rates of severe toxicities and is effective in inducing remission in R/R B-ALL. The findings support the ongoing development of CART22-65s and highlight the need to use it in combination with consolidation HSCT or other novel strategies.