Retrospective data were collected across centers participating in a real-world outcomes collaborative of CAR-T in ALL (ROCCA).
Published on the Journal of clinical Oncology:
Background:
Adults with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) face significant challenges and poor outcomes. Approximately half of adults with B-precursor ALL experience relapse following their initial treatment response.
The overall survival (OS) rate at one year drops to 26% after the administration of initial salvage therapy, and this rate further decreases with subsequent relapse episodes2. While allogeneic hematopoietic cell transplantation (Allo-HCT) remains a potentially curative therapy for relapsed disease, only a minority of patients proceed to transplant.
Development of non-transplant salvage therapies capable of producing durable remissions represents a critical need.
Here, we report outcomes of 76 adults with r/r B-ALL treated with post-approval brexu-cel at 13 U.S. centers.
Results:
Among 76 patients infused, median age was 44 yrs (range, 18-81); 54% were male, 57% were non-Hispanic White (25% Hispanic), and 71% had Ph-neg disease.
Prior to apheresis, 69% of patients had active disease (> 5% marrow blasts or presence of extramedullary disease), including 8 patients with CNS3 disease, 19% had detectable measurable residual disease (MRD) only, and 12% were MRD-neg.
Among 65 patients at least 28 days post-CAR-T with response assessed, 90.8% achieved CR/CRi, of whom 83% were MRD-neg, including CNS disease clearance in 7/8 CNS3 patients.
CRS and ICANS (ASTCT criteria) occurred in 81.6% (grade 3-4, 6.6%) and 59% (grade 3-4, 38.6%), respectively.
Median follow-up for survivors was 196.5 days (IQR 135.5-284.5). At last follow-up, 21 patients progressed/relapsed and 13 had died (7 of B-ALL; 6 of neurotoxicity/infection). Cumulative incidence of relapse and death in remission at 180 days were 31.5% (95% CI: 19.7%-44.1%) and 8.9% (95% CI: 3.5%-17.5%), respectively, while six-month PFS and OS were 58.8% (95% CI: 44.6%-70.5%) and 86.7% (95% CI: 75.8%-92.9%), respectively. Eleven patients underwent allogeneic transplant in CR/CRi after brexu-cel; all of whom remain in remission at last follow-up.
These data are the first to demonstrate post-approval efficacy and toxicity rates of brexu-cel in adults with r/r B-ALL. Unlike the ZUMA-3 population, 31% of patients infused in this real-world cohort lacked morphologically detectable disease and 8 had CNS3 prior to apheresis.
This data confirms high response rates associated with brexu-cel in adult ALL, but also highlight the need for interventions to reduce associated toxicities.
Furthermore, duration of response, particularly among patients achieving MRD-neg CR is promising and may be improved with maintenance/HCT, although larger cohorts with more follow-up are needed.
At the upcoming ASH 2023 conference in the coming December, the following RWE is expected to be published:
“Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) adult B-cell acute lymphoblastic leukemia (B-cell ALL): Evidence from the CIBMTR registry”.
Tecartus
Tecartus is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after two or more lines of systemic therapy including a Bruton’s tyrosine kinase (BTK) inhibitor unless ineligible to BTK inhibitor.
Limitation of use: Tecartus is not indicated for the treatment of patients with active central nervous system lymphoma.
Tecartus is indicated for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL).
For further information and full list of adverse events, please refer to the approved prescribing information as available at Israeli Ministry of Health website:
https://israeldrugs.health.gov.il/#!/byDrug
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form at https://sideeffects.health.gov.il/
Additionally, adverse events can be reported to Gilead: Safety_FC@gilead.com
This article is intended for healthcare providers only.
For any further questions please contact: medinfo.israel@gilead.com
© Gilead Sciences Israel Ltd. All rights reserved.
- Paul S, et al. Mayo Clin Proc. 2016; 91:1645-66.
- Gökbuget N, et al. Haematologica. 2016; 101:1524-44.
- Aldoss I, et al. J Oncol Pract. 2019; 15:65-75
IL-TEC-0171, DEC2023
