Tecartus (brexucabtagene autoleucel) - 2 indications

Scroll down for more information on each indication:

• for the treatment of adults with relapsed or refractory mantle cell lymphoma; approved July 2020
• for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia; approved September of 2021

General Information

Tecartus (brexucabtagene autoleucel) is a CD19-directed genetically modified autologous T cell immunotherapy.

Tecartus is specifically indicated for:

• the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL)
• the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Tecartus is supplied as a suspension for intravenous administration, for autologous use only. Do NOT use a leukodepleting filter. Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of Tecartus. Verify the patient’s identity prior to infusion. Premedicate with acetaminophen and diphenhydramine. Confirm availability of tocilizumab prior to infusion. Dosing of Tecartus is based on the number of chimeric antigen receptor (CAR)-positive viable T cells.

Scroll down for the recommended dosing/administration for each indication.

Mechanism of Action

Tecartus (brexucabtagene autoleucel) is a CD19-directed genetically modified autologous T cell immunotherapy. Tecartus binds to CD19-expressing cancer cells and normal B cells. Studies demonstrated that following anti-CD19 CAR T cell engagement with CD19-expressing target cells, the CD28 and CD3-zeta co-stimulatory domains activate downstream signaling cascades that lead to T cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines. This sequence of events leads to killing of CD19- expressing cells.

Side Effects

Adverse effects associated with the use of Tecartus may include, but are not limited to, the following:

• pyrexia
• CRS
• hypotension
• encephalopathy
• fatigue
• tachycardia
• arrhythmia
• infection – pathogen unspecified
• chills
• hypoxia
• cough
• tremor
• musculoskeletal pain
• headache
• nausea
• edema
• motor dysfunction
• constipation
• diarrhea
• decreased appetite
• dyspnea
• rash
• insomnia
• pleural effusion
• aphasia

The Tecartus drug label comes with the following Black Box Warning:

Cytokine Release Syndrome (CRS), including life threatening reactions, occurred in patients receiving Tecartus. Do not administer Tecartus to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. Neurologic toxicities, including life-threatening reactions, occurred in patients receiving Tecartus, including concurrently with CRS or after CRS resolution. Monitor for neurologic toxicities after treatment with Tecartus. Provide supportive care and/or corticosteroids, as needed. Tecartus is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Yescarta and Tecartus REMS Program.

Indication 1 - for the treatment of adults with relapsed or refractory mantle cell lymphoma

approved July 2020

Dosing/Administration

The Tecartus dose is 2 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 2 × 108 CAR-positive viable T cells. 

Clinical Trial Results

The FDA approval of Tecartus for mantle cell lymphoma was granted under accelerated approval based on overall response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. 

Accelerated approval was based on results of ZUMA-2, a single-arm, open-label study which enrolled 74 adult patients with relapsed or refractory MCL. All patients had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody therapy and a Bruton tyrosine kinase inhibitor (ibrutinib or acalabrutinib). The primary endpoint was objective response rate (ORR) per the Lugano Classification (2014), defined as the combined rate of CR and partial responses as assessed by an Independent Radiologic Review Committee (IRRC). In the study, 87% of patients (n=60 evaluable for efficacy analysis) responded to a single infusion of Tecartus, including 62% of patients who achieved a CR. Among all patients, follow-up was at least six months after their first objective disease response. Median duration of response has not yet been reached.

Indication 2 - for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia

approved September of 2021

Dosing/Administration

The target dose is 1 × 106 CAR-positive viable T cells per kg body weight, with a maximum of 1 × 108 CAR positive viable T cells.

Clinical Trial Results

FDA approval was  based on results from ZUMA-3, a global, multicenter, single-arm, open-label study in which 65% of the evaluable patients (n=54) achieved complete remission (CR) or CR with incomplete hematological recovery (CRi) at a median actual follow-up of 12.3 months. The duration of CR was estimated to exceed 12 months for more than half the patients. Among efficacy-evaluable patients, median duration of remission (DOR) was 13.6 months. Among the patients treated with Tecartus at the target dose (n=78), Grade 3 or higher cytokine release syndrome (CRS) and neurologic events occurred in 26% and 35% of patients, respectively, and were generally well-managed.