Durable B-ALL Control With Allogeneic Transplant After CAR T-Cell Therapy

Children and young adults who underwent an allogeneic hematopoietic stem cell transplant (alloHSCT) after achieving a complete response with CD19 CAR T cell therapy underwent durable B-cell control of acute lymphoblastic leukemia (B-ALL), according to the results of a phase 1 research (ClinicalTrials.gov Identifier: NCT01593696) published in the Journal of Clinical Oncology.

Although some of the patients undergoing CAR T cell therapy continue to receive alloHSCT, the study authors stated that [alloHSCT] after CD19-CAR T cell therapy to improve long-term outcomes in [children and young adults] has not been investigated. “

The phase 1 study evaluated 50 children and young adults with B-ALL who received CD19.2819 CAR T cell therapy. The primary goal was to determine the maximum tolerated dose of CAR T cells, the toxicity and the feasibility of generating CAR T cells in the study population. In addition, this analysis retrospectively evaluated the effect of alloHSCT on survival after CAR T cell therapy.

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At baseline, the median age was 13.5 years (range 4.3-30.4), and 40 (80%) of patients were male. The median number of prior regimens was 4 (range 4.3-30.4); 22 (44%) patients had at least 1 prior HSCT, 2 (4%) had prior CD19-targeted therapy, and 5 (10%) of patients had prior blinatumomab treatment.

A complete response was achieved in 31 (62%) of the patients. Of these patients, 28 (90.3%) were negative for minimal residual disease. Higher rates of complete response were associated with primary refractory disease, fewer prior lines of therapy, M1 marrow or fludarabine / cytarabine based lymphodepletion. The median overall survival was 10.5 months (95% CI, 6.3-29.2) during a median follow-up of 4.8 years.

Of the 28 patients who achieved a complete response, 21 (75%) underwent consolidative alloHSCT. The median overall survival for these patients was 70.2 months (95% CI, 10.4 – not estimated), with an event-free survival not yet reached. The relapse rate after alloHSCT was 4.8% (95% CI, 0.3-20.3) at 12 months and 9.5% (95% CI, 1.5-26.8) at 24 months.

Any grade cytokine release syndrome (CRS) developed in 35 (70%) patients, with 9 (18%) experiencing grade 3 to 4 CRS. Of the 10 patients (20%) who developed neurotoxicity, 4 were severe. One cardiac arrest occurred during CRS. All patients with CRS, neurotoxicity and cardiac arrest recovered.

The authors concluded that “… CD19.28ζ CAR T cells followed by a consolidating alloHSCT may provide long-term disease control in [children and young adults] with relapsed or refractory B-ALL. “

Disclosure: For a full description of authors’ affiliations, see the original reference.


Shah NN, Lee DW, Yates B, et al. Long-term follow-up of CD19-CAR T cell therapy in children and young adults with B-ALL. J Clin Oncol. Published online March 25, 2021.doi: org / 10.1200 / JCO.20.02262c

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