Final 10-Year Data Further Support CD22 CAR-T Therapy in R/R B-ALL

Long-term follow-up data from a decade-long phase 1 trial (NCT02315612) have shown continued efficacy of CD22-targeted chimeric antigen receptor (CAR) T-cell therapy as treatment for pediatric and young adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), regardless of disease burden.¹

The final 10-year data, published in Blood Advances, represent one of the most comprehensive longitudinal analyses of CD22 CAR T outcomes to date, highlighting both the treatment's efficacy and the critical role of consolidative hematopoietic stem cell transplant (HSCT) in maintaining durable remissions.

“Moving forward, CD22 CAR T cells will be critical for patients who relapse after CD19-targeting therapy or as part of combinatorial CAR T-cell strategies at initial relapse,” wrote Dreyzin et al, study authors.¹ “Increased access will require collaboration with pharmaceutical companies. The importance of CD22 CAR T cells as a potential curative therapy for children with refractory B-ALL remains a compelling reason to develop this therapy for commercial use.”

Efficacy Data and Toxicity Profile

Of 78 patients with B-ALL, 70.1% (n = 54) had achieved complete response by day 28, with 83.3% exhibiting minimal residual disease negativity. Median overall survival reached 13.6 months (95% CI, 10.3-20.7), and median relapse-free survival reached 6.1 months (95% CI, 4.7-11).

In terms of safety profile, cytokine release syndrome (CRS) occurred in 84.6% of patients, although the majority of cases were low grade (grade 1 or 2). Severe CRS (grade 3 or 4) was observed in 16.7% of the cohort. Of the total patient population, neurotoxicity occurred in 23.1% of patients, which was largely reversible. The rate of immune effector cell–associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) was 35.9%.

Notably, efficacy and safety did not vary significantly based on disease burden.

Study Design and Patient Characteristics

The study, initiated in 2014 and led by investigators at the National Cancer Institute,² has addressed a significant unmet need particularly in patients who relapse following CD19-directed therapies, such as tisagenlecleucel (tisa-cel; Kymriah), often due to "antigen escape" where leukemia cells no longer express the CD19 protein.

The study treated a total of 80 pediatric and young adult patients, including 78 with B-ALL and 2 with B-cell non-Hodgkin lymphoma. Among those with B-ALL, the median age was 15.8 years. Patients were heavily pretreated, having received a median of 6 previous lines of therapy, 65.4% undergoing HSCT, and 65.4% having previous CAR T cells. A large proportion of patients were classified as having a high disease burden (70.5%) based on the presence of bone marrow blasts.

Clinical Implications

These terminal findings further position CD22 CAR T-cell therapy as an important salvage option in the evolving treatment landscape of B-ALL, particularly for patients who have exhausted CD19-directed therapies. The consistent efficacy across varying levels of disease burden suggests that this approach may be viable even in patients with high leukemic involvement, a population that has historically been difficult to treat successfully.

Importantly, the manageable safety profile observed over the extended follow-up period adds to the growing body of evidence supporting the feasibility of CAR T-cell therapies in heavily pretreated pediatric and young adult populations. While toxicities such as CRS and neurotoxicity remain concerns, their generally reversible nature and predominance at lower grades provide reassurance for broader clinical application.

Looking ahead, investigators emphasized the need to optimize CD22 CAR T-cell constructs to improve persistence and reduce relapse risk. Strategies under exploration include dual-antigen targeting and sequential targeting approaches. Additionally, expanding access beyond academic centers will be essential to ensure that eligible patients can benefit from this therapy.

REFERENCES

1. Dreyzin A, Yates B, Shalabi H, et al. Ten-year experience of CD22 CAR T cells for children and young adults with B-cell acute lymphoblastic leukemia. Blood Advances. 2026;10(5):1700-1712. doi: 10.1182/bloodadvances.2025017753

2. Anti-CD22 chimeric receptor T cells in pediatric and young adults with recurrent or refractory CD22-expressing B cell malignancies. ClinicalTrials.gov. Updated March 13, 2026. Accessed March 20, 2026. https://clinicaltrials.gov/study/NCT02315612