Brexucabtagene Autoleucel (Tecartus)

Number: 0980

Policy

Note: REQUIRES PRECERTIFICATION

Precertification of brexucabtagene autoleucel (Tecartus) is required of all Aetna participating providers and members in applicable plan designs. For precertification, call 1-877-212-8811. 

Aetna considers brexucabtagene autoleucel (Tecartus) medically necessary for treatment of mantle cell lymphoma in members 18 years of age or older when all of the following criteria are met:

• The disease is relapsed or refractory; and
• The member has had previous treatment with both chemoimmunotherapy and a bruton tyrosine kinase inhibitor (e.g., ibrutinib); and
• The member has not received a previous treatment course of brexucabtagene autoleucel or another CD19-directed chimeric antigen receptor (CAR) T-cell therapy; and
• The B-cells must be CD19-positive as confirmed by testing or analysis.

Aetna considers all other indications for brexucabtagene autoleucel (Tecartus) experimental and investigational.

Dosing Recommendations

For autologous use only. For intravenous use only. 

Dosing of Tecartus is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. Each single infusion bag of Tecartus contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The dose is 2 × 10⁶ CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10⁸ CAR-positive viable T cells. 

See full prescribing information for dosing and administration details. 

Source: Kite Pharma, 2020.

Background

U.S. Food and Drug Administration (FDA)-Approved Indications

• Tecartus is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL).

On July 24, 2020, the FDA approved a chimeric antigen receptor (CAR) T-cell therapy, Tecartus (brexucabtagene autoleucel), for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL). The approval of brexucabtagene autoleucel (KTE-X19), is based on efficacy and safety data from the ongoing, single-arm, open-label, multicenter trial (ZUMA-2; NCT02601313), which evaluated the efficacy and safety of a single infusion in adult patients with relapsed or refractory mantle cell lymphoma (MCL) who had previously received anthracycline- or bendamustine-containing chemotherapy, an anti-CD20 antibody, and a Bruton tyrosine kinase inhibitor (BTKi; ibrutinib or acalabrutinib). The study excluded patients with active or serious infections, prior allogeneic hematopoietic stem cell transplant (HSCT), detectable cerebrospinal fluid malignant cells or brain metastases, and any history of central nervous system (CNS) lymphoma or CNS disorders (FDA 2020). 

Seventy-four patients were leukapheresed, five (7%) of whom did not begin conditioning chemotherapy or receive brexucabtagene autoleucel: three (4%) experienced manufacturing failure, one (1%) died of progressive disease, and one (1%) withdrew from the study. One patient (1%) received lymphodepleting chemotherapy but did not receive brexucabtagene autoleucel due to ongoing active atrial fibrillation. Sixty-eight of the patients who were leukapheresed received a single infusion of brexucabtagene autoleucel, and 60 of these patients were followed for at least six months after their first objective disease response, qualifying them as efficacy-evaluable. Among the 60 efficacy-evaluable patients, 2 × 10⁶ CAR-positive viable T cells/kg were administered to 54 (90%). The remaining six (10%) patients received doses of 1.0, 1.6, 1.8, 1.8, 1.9, and 1.9 × 10⁶ CAR-positive viable T cells/kg. Of the 60 efficacy-evaluable patients, the median age was 65 years (range: 38 to 79 years), 51 (85%) were male, and 56 (93%) were white. Most (50 patients; 83%) had stage IV disease. Twenty patients (33% of 60) had baseline bone marrow examinations performed per protocol; of these, ten (50%) were negative, eight (40%) were positive, and two (10%) were indeterminate. The median number of prior therapies among all 60 efficacy-evaluable patients was three (range: two to five). Twenty-six (43%) of the patients had relapsed after or were refractory to autologous HSCT. Twenty-one (35%) had relapsed after their last therapy for MCL, while 36 (60%) were refractory to their last therapy for MCL. Among the 60 efficacy-evaluable patients, 14 (23%) had blastoid MCL. Following leukapheresis and prior to administration of brexucabtagene autoleucel, 21 (35%) of the 60 patients received bridging therapy. Sixteen (27%) were treated with a BTKi, 9 (15%) with a corticosteroid, and 4 (7%) with both a BTKi and a corticosteroid. Among the 60 efficacy-evaluable patients, the median time from leukapheresis to product delivery was 15 days (range: 11 to 28 days), and the median time from leukapheresis to product infusion was 27 days (range: 19 to 63 days). The protocol-defined lymphodepleting chemotherapy regimen of cyclophosphamide 500 mg/m² intravenously and fludarabine 30 mg/m² intravenously, both given on each of the fifth, fourth, and third days before brexucabtagene autoleucel infusion, was administered to 53 (88%) of the 60 efficacy-evaluable patients. The remaining seven patients (12%) either received lymphodepletion over four or more days or received brexucabtagene autoleucel four or more days after completing lymphodepletion. All treated patients received brexucabtagene autoleucel infusion on Day 0 and were hospitalized until at least Day 7 (Kite Pharma, 2020).

The primary endpoint was objective response rate (ORR) per the Lugano Classification (2014) in patients treated with brexucabtagene autoleucel as determined by an independent review committee. According to published study results, the primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively (Wang 2020)

Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred. Tecartus is supplied in an infusion bag containing approximately 68 mL of frozen suspension of genetically modified autologous T cells in 5% DMSO and human serum albumin. It is intended for autologous use only and for intravenous 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 (Kite Pharma, 2020). 

Dosing of Tecartus is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. Each single infusion bag of Tecartus contains a suspension of chimeric antigen receptor (CAR)-positive T cells in approximately 68 mL. The dose is 2 × 10⁶ CAR-positive viable T cells per kg body weight, with a maximum of 2 × 10⁸ CAR-positive viable T cells (Kite Pharma, 2020). 

See full prescribing information for dosing and administration details.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+" :
CPT codes covered if selection criteria are met:
0537T	Chimeric antigen receptor T-cell (CAR-T) therapy; harvesting of blood-derived T lymphocytes for development of genetically modified autologous CAR-T cells, per day
0538T	preparation of blood-derived T lymphocytes for transportation (eg, cryopreservation, storage)
0539T	receipt and preparation of CAR-T cells for administration
0540T	CAR-T cell administration, autologous
Other CPT codes related to the CPB:
96413 - 96417	Intravenous chemotherapy administration
HCPCS codes covered if selection criteria are met:
C9073	Brexucabtagene autoleucel, up to 200 million autologous anti-cd19 car positive viable t cells, including leukapheresis and dose preparation procedures, per therapeutic dose
ICD-10 codes covered if selection criteria are met:
C83.10 - C83.19	Mantle cell lymphoma [relapsed or refractory]

The above policy is based on the following references: