CAR-T Cell Therapy Effective But Toxic in Acute Lymphoblastic Leukemia
Tisagenlecleucel, a CAR-T cell therapy being investigated for patients with B-cell ALL, showed significant efficacy in previous studies.
Tisagenlecleucel yields high remission rates among patients with B-cell acute lymphoblastic leukemia (ALL). Yet the drug comes with a significant toxicity profile, according to research published in The New England Journal of Medicine.1
Tisagenlecleucel, a chimeric antigen receptor (CAR)-T cell therapy being investigated for patients with B-cell ALL, showed significant efficacy in previous studies. The drug can provide durable remission, though adverse events (AEs) can be a serious problem with administration. Cytokine release syndrome is a particular concern with CAR-T cell therapy.
For this multi-center phase 2 study (ClinicalTrials.gov Identifier: NCT02435849), researchers evaluated the safety and efficacy among 75 patients with CD19-positive relapsed or refractory B-cell ALL. The primary endpoint was the overall remission rate.
Among the 75 patients who underwent tisagenlecleucel infusion, the median age was 11 years (range 3-23), the median number of previous therapies was 3 (range, 1-8), and the median marrow blast percentage was 74% (range, 5% to 99%). The median time from enrollment to infusion was 45 days.
The median follow-up was 13.1 months. The 3-month overall remission rate was 81%; all responders were negative for minimal residual disease. Forty-five patients (60%) had complete remission and 16 patients (21%) had complete remission with incomplete hematologic recovery. The median remission duration was not reached.
The 12-month event-free and overall survival rates were 50% and 76%, respectively.
Ninety-five percent of patients had an AE likely caused by tisagenlecleucel; 73% had a grade 3 or 4 AE likely caused to tisagenlecleucel. Cytokine release syndrome was reported in 77% of patients; nearly half (47%) of all patients were admitted to an ICU for a median of 7 days because of this syndrome.
Neurologic AEs were noted in 10 (13%) patients.
The authors concluded that “tisagenlecleucel produced high remission rates and durable remissions without additional therapy in high-risk pediatric and young adult patients with relapsed or refractory B-cell ALL. The risks associated with tisagenlecleucel are substantial, leading to ICU-level care in some cases, but were mitigated in most patients with supportive measures and cytokine blockade.”
- Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439-48. doi: 10.1056/NEJMoa1709866