Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. 71% patients achieved complete remission or complete remission with incomplete recovery following KTE-X19 infusion.

2. The majority of adverse events were mild, with two grade 5 KTE-X19-related events.

Evidence Rating Level: 2 (Good)

Study Rundown:

Refractory B-cell precursor acute lymphoblastic leukemia remains common despite advancements in treatment. Agents such as blinatumomab and inotuzumab, combined with allogeneic stem-cell transplant, are often used to achieve clinical remission in such patients. However, the 1-year survival rate and risk of remission continue to be concerning statistics. For these reasons, an alternative therapy must be looked into. This phase II open-label study aimed to report the safety and efficacy of KTE-X19 – a chimeric antigen receptor (CAR) T-cell therapy targeting the CD19 receptor – in adult patients with B-cell lymphoblastic leukemia. The primary outcome was the rate of complete remission or remission with incomplete recovery, while key secondary outcomes included minimal residual disease (MRD) negativity rate, duration of remission, and overall survival. According to study results, administration of KTE-X19 resulted in complete remission or remission with incomplete recovery in nearly three-quarters of patients in this study. Furthermore, MRD negativity was reported among the majority of patients, although the sample size was too low to ensure validity. This study suggests that KTE-X19 may serve as an important therapeutic option in patients with refractory B-cell lymphoblastic leukemia.

In-depth [randomized controlled trial]:

Between Oct 1, 2018, and Oct 9, 2019, 71 patients were enrolled and underwent leukapheresis from 25 centers in the USA, Canada, and Europe. Included patients were ≥18 years with an Eastern Cooperative Oncology Group (ECOG) rating of 0-1 and recurrent leukemia, defined as >5% lymphoblasts in the bone marrow. 16 patients were excluded due to the occurrence of adverse events and lack of eligibility from the study. Altogether, 55 patients received KTE-X19 and were included in the modified intention-to-treat analysis.

The median age among treated patients was 40 years (interquartile range [IQR] 28-52) while median follow-up time was 16.4 months (IQR 13.8-19.6). The primary outcome of overall clinical remission or remission with incomplete hematologic recovery was observed in 39 patients (71%, 95% confidence interval [CI] 57-82, p<0.0001) with 31 (56%) patients achieving complete remission. With regard to key secondary outcomes, patients remained in complete remission for a median duration of 12.8 months after receiving KTE-X19 and reported a median overall survival of 18.2 months since the administration of therapy. Moreover, MRD negativity was close to 100% (38 of 39, 97%) in patients who experienced clinical remission. The most common grade 3 or greater adverse events following infusion were anemia (49%), pyrexia (36%), and hypotension (29%). Although most events were mild in nature, two grade 5 events (brain herniation and septic shock) were reported. Overall, KTE-X19 showed promise in achieving complete remission and could be considered as a potential therapeutic option in patients with refractory B-cell acute lymphoblastic leukemia.

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