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

Although a proportion of patients who undergo CAR T-cell therapy go on to receive alloHSCT, the study authors stated that “The role for [alloHSCT] following CD19-CAR T-cell therapy to improve long-term outcomes in [children and young adults] has not been examined.”

The phase 1 trial evaluated 50 children and young adults with B-ALL who received CD19.28ζ CAR T-cell therapy. The primary objective was to determine the maximum tolerated dose of CAR T cells, toxicity, and 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.

Continue Reading

At baseline, the median age was 13.5 years (range, 4.3-30.4), and 40 (80%) of the 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 the patients had prior treatment with blinatumomab.

Complete response was achieved in 31 (62%) of the patients. Among 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 complete response, 21 (75%) proceeded to undergo consolidative alloHSCT. The median overall survival for these patients was 70.2 months (95% CI, 10.4-not estimable), with an event-free survival not yet reached. The rate of relapse 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 among 35 (70%) patients, with 9 (18%) experiencing grade 3 to 4 CRS. Of the 10 patients (20%) who developed neurotoxicity, 4 cases 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 consolidative alloHSCT can provide long-term durable disease control in [children and young adults] with relapsed or refractory B-ALL.”

Disclosure: Please see the original reference for a full disclosure of authors’ affiliations.


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