Which One is Better for Refractory/Relapsed Acute B-Cell Lymphoblastic Leukemia: Single-Target (CD19) or Dual-Target (Tandem or Sequential CD19/CD22) CAR T-Cell Therapy?

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Summary

CAR-T cells targeted to CD19 antigen on B cells have achieved great clinical results in B-cell acute lymphoblastic leukemia (B-ALL) treatment. Dual-target CAR-T cells were developed to decrease the possibility of relapse induced by antigen escape after receiving CD19 CAR-T therapy. Data from clinical trials showed that tandem CD19/CD22 CAR-T cells reached higher complete remission (CR) rates than single CD19 CAR-T cells and similar side effects. These results demonstrated that tandem CD19/CD22 CAR T-cell therapy is superior for B-ALL patients.

Research Description

Although anti-CD19 chimeric antigen receptor (CAR) T-cell therapies have produced 68%–93% remission in r/r B-cell acute lymphoblastic leukemia (B-ALL) patients after adoptive transfer, the limited 6.1 months of event-free survival time and CD19-negative relapse (25%–42%) is still a challenge for CAR-T therapy application. CD22 is another B cell antigen that shows similar expression features to CD19 and is applied to CAR therapy. Scientists have developed various CAR-T therapies targeting CD19 and CD22, including single CD19 CAR-T, single CD22 CAR-T, tandem CD19-CD22 CAR-T, and sequential infusion of CD19 CAR-T and CD22 CAR-T cells (sequential CD19/CD22).

By comparing data from 219 patients who received CAR-T treatments from clinical trials between 2018 to 2021, researchers found that bispecific CD19-CD22 tandem CAR-T obtained better therapeutic function than single CD19 CAR-T, while similar to sequential CD19/CD22 group.

Fig.1 Timeline of CAR-T therapy and patients' information for retrospective study.¹

Scientists analyzed each strategy on CR rate and MRD-negative CR rate and found that tandem CD19-CD22 CAR-T treatment produced better clinical response than single CD19 (98% vs. 83%) and sequential CD19/CD22 CAR-T strategies (95.2%). The CR rate was especially significant for patients with High-risk cellular and genetic mutations (100% vs. 82.4%).

Fig.2 Data on response rate to three kinds of CAR-T strategies.¹

Moreover, the tandem CD19-CD22 CAR-T group shows a prolonged OS (overall survival) and median LFS (leukemia-free survival) time than the single CD19 CAR-T and sequential CD19 and cd20 group. As a potential bridging technique for leukemia treatment, dual-target CD19-CD22 produced significantly higher OS than a single CD19 CAR-T, and the LFS and CIR were the same between the three groups.

As for adverse events, different grades of CRS, ICANS, and cytotoxicity to other organs have occurred, but there was no significant difference in the three groups.

Fig.3 The survival rate of patients receiving different CAR-T cells.¹

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Reference

Liu, S.; et al. Which one is better for refractory/relapsed acute B-cell lymphoblastic leukemia: Single-target (CD19) or dual-target (tandem or sequential CD19/CD22) CAR T-cell therapy? Blood Cancer J. 2023, 13: 60.