November 29, 2021

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What factors are related to the therapeutic effect of targeted CD19-CAR?

What factors are related to the therapeutic effect of targeted CD19-CAR?



The impact factor is as high as 44.5. The latest research: What factors are related to the therapeutic effect of targeted CD19-CAR?

For children and young patients with chemotherapy-refractory and recurrent B-cell acute lymphoblastic leukemia (B-ALL), immunotherapy targeting CD19 has achieved revolutionary results.

In particular, CD19-directed chimeric antigen receptor T cells (CD19-CAR) produced a very high complete remission rate (CR), reaching 70%-97%.

And Tisagenlecleucel was approved by the US Food and Drug Administration in 2017, and added tools for targeting B cells and other immunotherapeutics, such as the CD3-CD19 bispecific T cell adaptor antibody construct blinatumomab.

As a monotherapy, Blinatumomab induces a CR rate of 34%-69% in adults and 39% in children. The FDA also approves Blinatumomab for use in children with relapsed or refractory B-ALL, or in patients with 0.1% of CR patients with mild residual disease (MRD).

Although CD19 targeted therapy has achieved good results, recurrence is still a serious problem. In the clinical trial of Tisagenlecel, the 24-month recurrence-free survival rate (RFS) of patients who achieved CR was 62%.

Whether it is CD19-CAR or Blinatumomab, the common mechanism of recurrence is the down-regulation or escape of the target antigen. In view of the potential of CD19 regulation, continuous targeting of CD19 may increase the risk of unresponsiveness or relapse.

Due to concerns about CD19-negative escape, risk of recurrence, CD19-CAR non-response, and increased use of Blinatumomab and CD19-CAR, Professor Regina M Myers and his team have recently conducted related studies on these issues, trying to evaluate Blinatumomab exposure and follow-up The relationship between CD19-CAR treatment results.

What factors are related to the therapeutic effect of targeted CD19-CAR?

Researchers conducted a multicenter retrospective study on children and young patients with relapsed or refractory ALL who received CD19-CAR treatment from 2012 to 2019.

The main study endpoints are 6-month recurrence-free survival (RFS) and event-free survival (EFS), stratified according to the treatment plan of Blinatumomab.

Secondary goals include comparing long-term survival outcomes, complete remission rates, CD19 regulation, and identifying factors related to EFS. Of the 420 patients, 77 (18.3%) had previously received Blinatumomab treatment. Compared with patients who have not used Blinatumomab, patients exposed to Blinatummab have more frequent KMT2A rearrangements.

Among the patients with evaluable CD19-CAR response (n = 412), the complete response rate (20/31,64.5%) of patients who did not respond to Blinatumomab to CD19-CAR was lower than that of patients who responded to blinatumomab (39/42,92.9). %) or first-onset patients with blinatumomab (317/339,93.5%).

After CD19-CAR treatment, Blinatumomab non-responders had worse EFS for 6 months (27.3%; 95% CI, 13.6 ~ 43.0).

What factors are related to the therapeutic effect of targeted CD19-CAR?

Kaplan-Meier survival curve

This study is by far the largest series of studies in children’s CD19-CAR studies and the first study on the effects of continuous targeting of CD19.

The study proved that: Blinatumomab non-response and high disease burden are independently associated with poor RFS and EFS, and determine an important indicator of long-term prognosis after CD19-CAR.

Reference:

Myers RM, Taraseviciute A,et al. Blinatumomab Nonresponse and High-Disease Burden Are Associated With Inferior Outcomes After CD19-CAR for B-ALL. J Clin Oncol. 2021 Nov 12:JCO2101405. doi: 10.1200/JCO.21.01405. Epub ahead of print. PMID: 34767461.

What factors are related to the therapeutic effect of targeted CD19-CAR?

(source:internet, reference only)


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