In a study reported in the Journal of Clinical Oncology, Myers et al found that lack of response to prior blinatumomab treatment was associated with poorer outcomes with CD19-targeted chimeric antigen receptor (CAR) T-cell therapy (CD19-CAR) in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
As stated by the investigators, “CD19-CAR and blinatumomab effectively induce remission in relapsed or refractory B-cell acute lymphoblastic leukemia but are also associated with CD19 antigen modulation. There are limited data regarding the impact of prior blinatumomab exposure on subsequent CD19-CAR outcomes.”
Study Details
The retrospective study involved data on 420 patients (median age = 12.7 years, interquartile range = 7.1–17.5 years) treated with commercial tisagenlecleucel or one of three investigational CD19-CAR products between 2012 and 2019 at seven U.S. centers. The primary outcome measures were 6-month event-free and relapse-free survival according to blinatumomab use.
Key Findings
Among the 420 patients, 77 (18.3%) received prior treatment with blinatumomab. Those who received blinatumomab were more likely to harbor KMT2A rearrangements (14.3% vs 6.7%, P = .04) and to have undergone hematopoietic stem cell transplantation (51.9% vs 34.7%, P = .006) vs blinatumomab-naive patients.
Among 412 patients evaluable for response to CD19-CAR, complete remission rates were significantly lower (overall P < .0001) among blinatumomab nonresponders (20 of 31, 64.5%) vs blinatumomab responders (39 of 42, 92.9%) and blinatumomab-naive patients (317 of 339, 93.5%).
Following CD19-CAR, blinatumomab nonresponders had poorer 6-month event-free survival (27.3%, 95% confidence interval [CI] = 13.6%–43.0%) vs blinatumomab responders (66.9%, 95% CI = 50.6%–78.9%, P < .0001) and blinatumomab-naive patients (72.6%, 95% CI = 67.5%–77.0%, P < .0001). Blinatumomab nonresponders also had poorer 6-month relapse-free survival (45.4%, 95% CI = 23.4%–65.1%) vs blinatumomab responders (73.8%, 95% CI = 56.8%–85.0%, P = .0004) and blinatumomab-naive patients (81.1%, 95% CI = 76.3%–85.0%; P < .0001).
Among 414 patients with available data, CD19-dim or partial expression prior to CD19-CAR was more common in blinatumomab-treated patients vs blinatumomab-naive patients (13.3% vs 6.5%, P = .06) and was associated with poorer event-free and relapse-free survival.
Among all patients, high disease burden was independently associated with significantly poorer event-free survival (P < .0001) and relapse-free survival (P < .0001).
The investigators concluded, “With the largest series to date in pediatric CD19-CAR, and, to our knowledge, the first to study the impact of sequential CD19 targeting, we demonstrate that blinatumomab nonresponse and high disease burden were independently associated with worse relapse-free and event-free survival, identifying important indicators of long-term outcomes following CD19-CAR.”
Nirali N. Shah, MD, MHSc, of the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute Center for Cancer Research, and Warren Grant Magnuson Clinical Center. For full disclosures of the study authors, visit ascopubs.org.
