A CAR T-cell therapy brexucabtagene autoleucel as a treatment for adult patients with relapsed/refractory mantle cell lymphoma.
Brexucabtagene autoleucel approved as a treatment for adult patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.
Brexucabtagene autoleucel consists of an anti-CD19 single-chain variable fragment with a CD3 zeta T-cell activation domain and a CD28 signaling domain.
Tradename Tecartus.
The approval is based on findings from the phase 3 ZUMA-trial, in which a single infusion of the CAR T-cell product elicited an 87% objective response rate, with 52% complete response (CR) rate.
Grade 3 cytokine release syndrome (CRS) and neurologic events were reported in 18% and 37% of patients, respectively.
Overall, KTE-X19 was effectively manufactured for 96% of patients and administered to 92%.
Beginning 5 days prior to T-cell infusion, patients received 3 consecutive days of conditioning chemotherapy with fludarabine at 30 mg/m2 plus cyclophosphamide at 500 mg/m2.
KTE-X19 was administered as a single infusion at 2 x 106 cells.
The median duration of response had not yet been reached at the time of analysis, and of those reaching a CR, 78% remained in remission at the time of the analysis.
At the median follow-up of 27.0 months, 43% of responders remained in remission, which suggested high durability of response with a plateau in the curve.
A 12-month OS rate of 83%.
Adverse events: pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%).
All-grade cytokine release syndrome occurred in 91% of patients.
Management for CRS included tocilizumab or corticosteroids
The median time to onset was 2 days and the median duration of CRS was 11 days.
All-grade neurotoxicity was experienced by 63% of patients
The most common symptoms were tremor (35%), encephalopathy (31%), and confusion (21%).
For relapse/ refractory ALL :
Phase 1/2 ZUMA-3 study which showed that at a median follow-up of 16.4 months with a single infusion of the CAR T-cell therapy elicited a high and durable response rate in heavily pretreated patients with relapsed/refractory B-ALL, the majority of whom had a high disease burden.
The phase 2 portion of the trial showed that brexucabtagene autoleucel elicited a complete response/complete response with incomplete blood count recovery (CR/CRi) rate of 70.9%, which included a CR rate of 56.4%.
Brexucabtagene autoleucel had a manageable toxicity profile with an overall CR/CRi rate of 83%.
The recommended phase 2 dose of the CAR T-cell product was determined to be 1 x 106 CAR T cells/kg.
The median time to initial CR/CRi was 1.1 months.
In responders, the MRD negativity rate with the CAR T-cell therapy was 97%.
Eighteen percent of patients received ASCT at a median of 98 days after having received the CAR T product.
The median DOR was 12.8 months, with or without subsequent ASCT.
As of data cutoff, 31% of the patients who achieved a CR or CRi experienced ongoing remissions without receiving subsequent ASCT.
The median relapse free survival 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): anemia (49%) and pyrexia (36%).
Cases of grade 5 AEs: included brain herniation and septic shock.
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.
Treatment of these AEs, patients were given tocilizumab (Actemra; 80%), steroids (75%), and vasopressors (40%).