CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a high initial response in patients with B-cell acute lymphoblastic leukemia (B-ALL), but most patients still progress after CAR-T therapy. Patients who progress have a poor prognosis, despite some achieving remission after salvage therapy, and this remains an unmet clinical need, according to research published in Blood.

Patients with relapsed/refractory B-ALL have high rates of adverse events with CAR-T therapy, and 30% to 60% eventually relapse. The researchers described the clinical characteristics and outcomes of patients with B-ALL who progressed after CD19 CAR-T therapy.

A total of 56 adult patients received CAR T-cell therapy at Memorial Sloan Kettering Cancer Center (MSKCC). There were 45 patients who achieved complete remission (CR). A total of 38 patients (68%) relapsed during a median follow-up period of 44.7 months; 9 of those patients were refractory to the CAR-T therapy.

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The median overall survival (OS) was 13 months, with a 3-year event-free survival (EFS) of 16.1% for the entire cohort. Of the 38 patients who relapsed, 21 (55%) had high-risk cytogenetic abnormalities.

The median time from CAR-T therapy to relapse was 6.6 months.

Higher disease burden before CAR-T therapy was the only risk factor significantly associated with relapse (hazard ratio [HR], 2.2; P =.02). Prior treatment with blinatumomab or inotuzumab was not significantly associated with relapse risk and OS after progression after CAR-T therapy.

A total of 30 of the 38 patients who progressed received salvage treatment: 6 received multiagent chemotherapy, 18 received nonintensive therapy, 3 received blinatumomab or inotuzumab, and 3 received CAR-T reinfusion as the first salvage therapy.

There were 24 patients who were available for evaluation, 8 achieved CR after the first salvage therapy, 4 achieved CR after a second salvage therapy, and 1 achieved CR after 3 or more lines of salvage treatment. Patients who achieved CR with salvage therapy had a median OS of 16.2 months compared with a median OS of 4.6 months for patients who did not respond to salvage treatment.

Of the 38 patients who progressed after CAR T-cell therapy, 82% (31 patients) died. The median OS was 7.5 months.

The authors recommend that future studies evaluate the optimal sequence of antibody-based and cellular immunotherapies in patients with B-ALL.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Wudhikarn K, Flynn JR, Rivière I, et al. Interventions and outcomes of adult patients with B-ALL progressing after CD19 chimeric antigen receptor T-cell therapy. Blood. 2021;138(7):531-543. doi:10.1182/blood.2020009515