FDA Approves Brexucabtagene Autoleucel for B-Cell Precursor Acute Lymphoblastic Leukemia

The FDA has approved brexucabtagene autoleucel (Tecartus; formerly KTE-X19) for the treatment of relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (B-ALL).¹

The approval was based on findings from the phase 1/2 ZUMA-3 study, which showed that at a median follow-up of 16.4 months (range, 10.3-22.1), a single infusion of the chimeric antigen receptor (CAR) T-cell therapy produced a high and durable response rate in heavily pretreated patients with R/R B-ALL. Most of the patients had a high disease burden.²

Data presented during the 2021 ASCO Annual Meeting showed that brexucabtagene autoleucel produced a complete response/complete response with incomplete blood count recovery (CR/CRi) rate of 70.9%, including a CR rate of 56.4%.

“Adults with ALL face a significantly poorer prognosis compared to children, and roughly half of all adults with B-ALL will relapse on currently available therapies,” said Bijal Shah, MD, ZUMA-3 investigator and medical oncologist, Moffitt Cancer Center, Tampa, Florida, in a press release. “We now have a new meaningful advancement in treatment for these patients. A single infusion of Tecartus has demonstrated durable responses, suggesting the potential for long-term remission and a new approach to care.”

The international, multicenter, phase 1/2 trial included patients who were at least 18 years of age with R/R B-ALL and bone marrow blasts that were greater than 5%, and who were not previously treated with blinatumomab (Blincyto).

In the phase 2 portion of the trial, 71 patients received conditioning chemotherapy of fludarabine 25 mg/m2 on days -4, -3, and -2, and cyclophosphamide at 900 mg/m2 on day -2. A single infusion of the CAR T-cell therapy was administered on day 0 at a dose of 1 x 106 anti-CD19 CAR T cells/kg.

The primary end point of the trial was CR/CRi rate by central assessment. Key secondary end points included minimal residual disease (MRD) negativity rate, duration of response (DOR), relapse-free survival (RFS), overall survival, safety, and CAR T-cell levels in the blood and cytokine levels in serum.

Of the 71 patients enrolled to the trial, 14 patients did not receive treatment because of toxicities (n = 7), eligibility criteria were not met (n = 3), product was not available (n = 1), patient consent was withdrawn (n = 1), or for other reasons not specified (n = 2). A total of 57 patients received conditioning chemotherapy, 2 of whom did not receive treatment afterward.

The median time to initial CR/CRi was 1.1 months (range, 0.85-2.99). In responders, the MRD negativity rate with the CAR T-cell therapy was 97%, with a sample unavailable for 1 patient. Eighteen percent of patients received ASCT at a median of 98 days (range, 60-207) after having received the CAR T product.

The median DOR was 12.8 months, with or without censoring patients at subsequent ASCT. As of data cutoff, 31% of the patients who achieved a CR or CRi experienced ongoing remissions without receiving subsequent ASCT. Additionally, the median RFS was 11.6 months and 14.2 months for those who achieved a CR/CRi.

The most common grade 3 or higher adverse effects (AEs) included anemia (49%) and pyrexia (36%). Ten cases of grade 5 AEs were reported, 4 of which were ALL; 2 were treatment-emergent from the CAR T-cell product and included brain herniation and septic shock; 3 occurred after initiation of another cancer treatment and included fungal pneumonia, sepsis, and respiratory failure; and 1 was pneumonia unrelated to treatment with brexucabtagene autoleucel.

No grade 5 cytokine release syndrome (CRS) or other neurological AEs were reported. However, 24% of patients experienced grade 3 or higher CRS and 25% reported other grade 3 or higher neurological events. To treat these AEs, patients were given tocilizumab (Actemra; 80%), steroids (75%), and vasopressors (40%).

“Today marks Kite’s fourth FDA approved indication in cell therapy in under four years, demonstrating our commitment to advancing CAR T for patients across many different hematologic malignancies,” said Christi Shaw, chief executive officer of Kite, in a press release. “Tecartus has already transformed outcomes for adults living with mantle cell lymphoma, and we look forward to offering the hope for a cure to patients with ALL.”

References

1. U.S. FDA Approves Kite’s Tecartus® as the First and Only Car T for Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia. Kite. News release. Published October 1, 2021. Accessed October 1, 2021. https://bwnews.pr/3iq0Chg.
2. Shah B, Ghobadi A, Oluwole O, et al. Phase 2 results of the ZUMA-3 study evaluating KTE-X19, an anti-CD19 chimeric antigen receptor T-cell therapy, in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia. J Clin Oncol. 2021;39(15):7002-7002. doi:10.1200/JCO.2021.39.15_suppl.7002