Obecabtagene Autoleucel (Aucatzyl)

Number: 1072

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses obecabtagene autoleucel (Aucatzyl) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of obecabtagene autoleucel (Aucatzyl) is required of all Aetna participating providers and members in applicable plan designs. For precertification of obecabtagene autoleucel (Aucatzyl), contact National Medical Excellence (NME) at 877-212-8811.  

1. Exclusions 

   Aetna will not provide coverage for members with any of the following exclusions:

   1. Age less than 18 years; or
   2. ECOG performance status greater than or equal to 3 (member is not ambulatory and not capable of all self-care, confined to bed or chair more than 50% of waking hours); or
   3. Inadequate and unstable kidney, liver, pulmonary or cardiac function; or
   4. Active hepatitis B, active hepatitis C or any active uncontrolled infection; or
   5. Active inflammatory disorder; or
   6. History or presence of clinically relevant central nervous system (CNS) pathology; or
   7. Active graft versus host disease.

2. Criteria for Initial Approval

   Adult Relapsed or Refractory B-cell precursor Acute Lymphoblastic Leukemia (ALL)

   Aetna considers obecabtagene autoleucel (Aucatzyl) medically necessary for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) when all of the following criteria are met:

   1. The member has not received a previous treatment course of the requested medication or another CD19-directed chimeric antigen receptor (CAR-T) therapy, or any prior CD19 directed therapy other than blinatumomab; and
   2. The member meets either of the following criteria:

      1.  Member has Philadelphia chromosome-negative disease that is relapsed or refractory as defined as one of the following:

         1. Primary refractory disease; or
         2. First relapse with remission of 12 months or less; or
         3. Relapsed or refractory disease after at least 2 previous lines of systemic therapy; or
         4. Relapsed or refractory disease after allogeneic stem cell transplant (allo-SCT); or

      2. Member has Philadelphia chromosome-positive disease and meets any of the following:

         1. The member has relapsed or refractory disease despite treatment with at least 2 different tyrosine kinase inhibitors (TKIs) (e.g., bosutinib, dasatinib, imatinib, nilotinib, ponatinib) or one line of second-generation TKI; or
         2. The member is intolerant to TKI therapy or TKI therapy is contraindicated; and

      3. The member has morphological disease in the bone marrow (greater than or equal to 5% blasts).

   Aetna considers all other indications as experimental, investigational, or unproven.

3. Continuation of Therapy

   See Dosage and Administration information.

Dosage and Administration

Obecabtagene autoleucel is supplied as Aucatzyl cell suspension for autologous intravenous infusion only. Aucatzyl contains a total recommended dose of 410 x 10⁶ CD19 CAR-positive viable T cells supplied in 3 to 5 infusion bags.

Do not use a leukodepleting filter.

Prior to infusion:

• Administer a lymphodepleting chemotherapy regimen of fludarabine/cyclophosphamide.
• Ensure availability of bone marrow assessment results from a sample obtained within 7 days prior to start of lymphodepleting chemotherapy.
• Premedicate with acetaminophen.
• Confirm availability of tocilizumab prior to infusion.

Aucatzyl dose and administration:

• Verify person’s identity prior to infusion;
• Dosing is based on the Dose Schedule Planner provided in the shipper and via Autolus's Scheduling Portal;
• The total recommended dose of Aucatzyl is 410 x 10⁶ CD19 chimeric antigen receptor (CAR)-positive viable T cells;
• The treatment regimen consists of a split dose infusion to be administered on Day 1 and Day 10 (± 2 days). Dose to be administered is determined by the person bone marrow blast assessment;
• See full prescribing information for important preparation and administration information.

Source: Autolus, 2024

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
38225 – 38228	Chimeric antigen receptor T-cell (CAR-T) therapy
96413 - 96415	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
Obecabtagene autoleucel – No specific code
Other HCPCS codes related to the CPB:
Bosutinib, dasatinib, nilotinib, ponatinib – No specific code
J9039	Injection, blinatumomab, 1 microgram
S0088	Imatinib, 100 mg
ICD-10 codes covered if selection criteria are met:
C91.00	Acute lymphoblastic leukemia not having achieved remission [B-cell precursor]
C91.02	Acute lymphoblastic leukemia, in relapse [B-cell precursor]
ICD-10 codes not covered for indications listed in the CPB:
A00.0 – B99.9	Certain infectious and parasitic diseases
D89.810 – D89.813	Graft-versus-host disease
K50.00 – K52.9	Noninfective enteritis and colitis
L00 – L08.9	Infections of the skin and subcutaneous tissue
M00.00 – M02.9	Infectious arthropathies
M04.1 – M04.9	Autoinflammatory syndromes
M05.00 - M1A.9XX1	Inflammatory polyarthropathies
M35.81	Multisystem inflammatory syndrome
R94.01 – R94.09	Abnormal results of function studies of central nervous system
R94.2	Abnormal results of pulmonary function studies
R94.30 – R94.39	Abnormal results of cardiovascular function studies
R94.4	Abnormal results of kidney function studies
R94.5	Abnormal results of liver function studies
T80.211A - T80.29XS	Infections following infusion, transfusion and therapeutic injection
T81.40XA - T81.49XS	Infection following a procedure
T82.6XXA - T82.7XXS	Infection and inflammatory reaction due to cardiac valve prosthesis, other cardiac and vascular devices, implants and grafts
T83.510A - T83.69XS	Infection and inflammatory reaction due to prosthetic device, implant and graft in urinary system and genital tract
T84.50XA - T84.7XXS	Infection and inflammatory reaction due to internal joint prosthesis, internal fixation device, other internal orthopedic prosthetic devices, implants and grafts
T85.71XA - T85.79XS	Infection and inflammatory reaction due to other internal prosthetic devices, implants and grafts
T86.03	Bone marrow transplant infection
T86.13	Kidney transplant infection
T86.23	Heart transplant infection
T86.33	Heart-lung transplant infection
T86.43	Liver transplant infection
T86.812	Lung transplant infection
T86.822	Skin graft (allograft) (autograft) infection
T86.832	Bone graft infection
T86.8421 – T86.8429	Corneal transplant infection
T86.852	Intestine transplant infection
T86.892	Other transplanted tissue infection
T86.93	Unspecified transplanted organ and tissue infection
T87.40 – T87.44	Infection of amputation stump
T88.0XXA - T88.0XXS	Infection following immunization
Z79.622	Long term (current) use of Janus kinase inhibitor
Z86.61	Personal history of infections of the central nervous system

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Background

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

• Adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Obecabtagene autoleucel is available as Aucatzyl (Autolus Inc., 2024), a CD19-direcgted genetically modified autologous T cell immunotherapy made up of the patient's own T cells (i.e., prepared from the patient's own peripheral blood mononuclear cells collected by a standard leukapheresis procedure) that are transferred with a lentiviral vector to express an anti-CD19 chimeric antigen receptor (CAR). The CAR consists of a murine anti-CD19 single chain variable fragment (scFv) linked to 4-IBB and CD3-zeta co-stimulatory domains. The anti-CD19 CAR-positive T cells engage with target cells expressing CD19, such as cancer cells and normal B cells, resulting in activation of the anti-CD19 CAR-positive T cells and downstream signaling through the CD3-zeta domain. Following their activation, proliferation and persistence by anti-CD19 CAR-positive T cells are enhanced by the presence of the 4-IBB co-stimulatory domain. This binding to CD19 results in anti-tumor activity and killing of CD19-expressing target cells (Autolus, 2024).

According to the prescribing information, Aucatzyl carries the following boxed warnings:

• Cytokine release syndrome (CRS), occurred in patients receiving Aucatzyl. Do not administer Aucatzyl to patients with active infection or inflammatory disorders. Prior to administering Aucatzyl, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage CRS.
• Immune effector cell-associated neurotoxicity syndrome (ICANS), including fatal or life-threatening reactions, occurred in patients receiving Aucatzyl, including concurrently with CRS or after CRS resolution. Monitor for neurologic signs and symptoms after treatment with Aucatzyl. Prior to administering Aucatzyl, ensure that healthcare providers have immediate access to medications and resuscitative equipment to manage neurologic toxicities.
• T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies.

Additionally, the prescribing information notes the following warnings and precautions and adverse reactions:

• Warnings and precautions

  • Prolonged cytopenias: Patients may exhibit Grade 3 or higher cytopenias for several weeks following Aucatzyl infusion. Monitor complete blood counts.
  • Infections: Monitor patients for signs and symptoms of infection; treat appropriately.
  • Hypogammaglobulinemia: Monitor and consider immunoglobulin replacement therapy.
  • Hemophagocytic lymphohistiocytosis/ macrophage activation syndrome: Administer treatment per institutional standards.
  • Hypersensitivity reactions: Monitor for hypersensitivity reactions during infusion.
  • Secondary malignancies: T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies. In the event that a secondary malignancy occurs after treatment with Aucatzyl, contact the manufacturer.
  • Effects on ability to drive and use machines: Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks after receiving Aucatzyl.

• Adverse reactions

  • The most common (non-laboratory) adverse reactions (incidence ≥ 20%) are: CRS, infections - pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.

On November 8, 2024, the U.S. Food and Drug Administration (FDA) approved obecabtagene autoleucel (Aucatzyl), a CD19-directed genetically modified autologous T cell immunotherapy, for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The FDA approval was based on supporting data from the FELIX study (FDA, 2024).

In the FELIX study, an open-label, multi-center, single-arm trial, investigators evaluated the efficacy of obecabtagene autoleucel (Aucatzyl) in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Patients enrolled in the study were required to have refractory ALL, first relapse following a remission lasting 12 months or less, relapsed or refractory ALL following two or more prior lines of systemic therapy, or relapsed or refractory disease at least 3 or more months after allogeneic stem cell transplantation (SCT) and have disease burden of ≥ 5% blasts in bone marrow at screening. The study excluded patients with isolated extra medullary disease, active or serious infections requiring systemic antimicrobials, active graft versus host disease, history or presence of CNS disorders (Autolus, 2024; FDA, 2024).

Treatment was given in the in-patient setting and consisted of lymphodepleting chemotherapy (fludarabine 30 mg/m² IV daily for 4 days; cyclophosphamide 500 mg/m² IV daily for 2 days starting with first dose of fludarabine) followed by Aucatzyl as a split dose infusion with a total recommended dose of 410 × 10⁶ CD19 CAR-positive viable T cells (Autolus, 2024).

The major efficacy outcome measures included rate and duration of complete remission (CR) achieved within 3 months after infusion. Additional outcome measures were rate and duration of overall complete remission which includes complete remission and complete remission with incomplete hematologic recovery, at any time. Among the 65 patients evaluable for efficacy, 27patients (42%; 95% confidence interval [CI]: 29%, 54%) achieved CR within 3 months. The median duration of CR achieved within 3 months was 14.1 months (95% CI: 6.1, not reached). Among patients in the efficacy evaluable population in whom best response was complete remission with incomplete hematologic recovery “At Anytime” (N=8; 12%), the median duration of remission was 10.5 months (95% CI: 1.8, NR) (Autolus, 2024; FDA, 2024).

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References