Ciltacabtagene Autoleucel (Carvykti)

Number: 1007

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 ciltacabtagene autoleucel (Carvykti) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

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

1. Criteria for Initial Approval

   Multiple Myeloma

   Aetna considers ciltacabtagene autoleucel (Carvykti) medically necessary for treatment of relapsed or refractory multiple myeloma in members 18 years of age and older when all of the following criteria are met:  

   1. The member has received prior treatment with at least one line of therapy, including at least one drug from each of the following categories:

      1. Immunomodulatory agent; and 
      2. Proteasome inhibitor; and
   2. The disease is lenalidomide-refractory; and
   3. The member has not received previous treatment with the requested medication or another CAR-T therapy directed at any target; and
   4. The member has an ECOG performance status of 0 to 2; and
   5. The member has adequate and stable kidney, liver, pulmonary and cardiac function; and
   6. The member does not have known active or prior history of central nervous system (CNS) involvement, including CNS multiple myeloma; and
   7. The member does not have clinically significant active infection; and
   8. The member does not have active graft versus host disease; and
   9. The member does not have an active inflammatory disorder.

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

2. Continuation of Therapy

   See Dosage and Administration information.

Dosage and Administration

Ciltacabtagene autoleucel (Carvykti) is a cell suspension for autologous and intravenous use only and administered at a certified healthcare facility. A single dose of Carvykti contains a cell suspension of 0.5 to 1.0 x 10⁶ CAR-positive viable T cells per kg body weight in one infusion bag. 

Multiple Myeloma

Carvykti is administered as single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive viable T cells in one infusion bag. The dosage recommended is 0.5 to 1.0 x 10⁶ CAR-positive viable T cells per kg of body weight, with a maximum dose of 1 x 10⁸ CAR-positive viable T cells per single infusion.

Source: Janssen Biotech, 2023

Experimental, Investigational, or Unproven

Aetna considers ciltacabtagene autoleucel experimental, investigational, or unproven for the treatment of solid tumors.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
0537T	Chimeric antigen receptor T-hyphencell (CAR-hyphenT) therapy; harvesting of blood-hyphenderived T lymphocytes for development of genetically modified autologous CAR-hyphenT cells, per day
0538T	Chimeric antigen receptor T-hyphencell (CAR-hyphenT) therapy; preparation of blood-hyphenderived T lymphocytes for transportation (eg, cryopreservation, storage)
0539T	Chimeric antigen receptor T-hyphencell (CAR-hyphenT) therapy; receipt and preparation of CAR-hyphenT cells for administration
0540T	Chimeric antigen receptor T-hyphencell (CAR-hyphenT) therapy; CAR-hyphenT cell administration, autologous
96413 – 96417	Chemotherapy administration, intravenous infusion technique
HCPCS codes covered if selection criteria are met:
Q2056	Ciltacabtagene autoleucel, up to 100 million autologous b-cell maturation antigen (bcma) directed car-positive t cells, including leukapheresis and dose preparation procedures, per therapeutic dose
Other HCPCS codes related to the CPB:
J9041	Injection, bortezomib, 0.1 mg
J9044	Injection, bortezomib, not otherwise specified, 0.1 mg
J9046	Injection, bortezomib, (dr. reddy's), not therapeutically equivalent to J9041, 0.1 mg
J9047	Injection, carfilzomib, 1 mg
J9048	Injection, bortezomib (fresenius kabi), not therapeutically equivalent to J9041, 0.1 mg
J9049	Injection, bortezomib (hospira), not therapeutically equivalent to J9041, 0.1 mg
J9051	Injection, bortezomib (maia), not therapeutically equivalent to j9041, 0.1 mg
J9145	Injection, daratumumab, 10 mg
ICD-10 codes covered if selection criteria are met:
C90.00 - C90.02	Multiple myeloma [relapsed or refractory]
C90.10	Plasma cell leukemia not having achieved remission
ICD-10 codes not covered for indications listed in the CPB:
C00.0 –C88.9, C90.20 – C90.32, C96.0 - D09.9	Malignant solid tumors

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Background

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

• Carvykti is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.

Ciltacabtagene autoleucel is available as Carvykti (Janssen Biotech, Inc.) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy product made up of a patient’s own T cells that are harvested and genetically modified. Carvykti is prepared from the patient’s peripheral blood mononuclear cells (PBMCs), which are obtained from a standard leukapheresis procedure. Carvykti's mechanism of action involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor (CAR) that recognizes and destroys cells that express BCMA. With Carvykti binding to BCMA-expressing cells, the CAR stimulates T cell activation, expansion, and elimination of target cells (Janssen Biotech).

According to the prescribing information, Carvykti carries the following black box warnings:

• Cytokine release syndrome (CRS), including fatal or life-threatening reactions. In clinical trial, CRS was noted in 95% (92/97) of patients receiving Carvykti. Grade 3 or higher CRS was noted in 5% (5/97) of patients, with grade 5 CRS noted in 1 patient.
• Immune effector cell-associated neurotoxicity syndrome (ICANS).
• Parkinsonism and Guillain-Barré syndrome and their associated complications.
• Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), including fatal and life-threatening reactions.
• Prolonged and/or recurrent cytopenias with bleeding and infection. 

Additional warnings and precautions include: prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, and effects on ability to drive and use machines.

Per the prescribing information, the most common nonlaboratory adverse reactions (incidence greater than 20%) were pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.

On February 28, 2022, the U.S. Food and Drug Administration (FDA) approved Carvykti (ciltacabtagene autoleucel) for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The FDA granted priority review, breakthrough designation and orphan drug designation for Carvykti and the FDA approval was based on supporting data from the pivotal CARTITUDE-1 study. 

In the CARTITUDE-1 study, an open-label, single-arm, multicenter phase 1b/2 trial, Berdeja and colleagues (2021) evaluated the safety and efficacy of ciltacabtagene autoleucel (cilta-cel) in patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteosome inhibitor, immunomodulatory drug, and anti-CD38 antibody. In this study 97 patients (29 in phase 1b and 68 in phase 2) received a cilta-cel infusion at the target phase 2 dose of 0.75 x 106 CAR-positive viable T cells per kg (range 0.5x106-1.0x106). The median number of prior lines of therapy was 6 with 82% of patients receiving 4 or more lines of therapy. Primary endpoints included safety and confirmation of the recommended phase 2 dose (phase 1b), and overall response rate (phase 2) in all patients receiving treatment. Notable secondary endpoints included duration of response and progression-free survival. Median follow-up was 12.4 months (Interquartile Range [IQR] 10.6-15.2). Overall response rate was 97% (95% Confidence Interval [CI] 91.2-99.4; 94 of 97 patients); 65 (67%) achieved stringent complete response; time to first response was 1 month (IQR 0.9-1.0). Among the 95 patients who responded, the median duration of response was 21.8 months (95% CI 21.8-not estimable). Progression-free survival was not reached (16.8-not estimable). The 12-month progression-free rate was 77% (95% CI 66.0-84.3) and overall survival rate was 89% (80.2-93.5). Grade 3-4 hematological adverse events included neutropenia (92 [95%] of 97 patients), anemia (66 [68%]), leukopenia (59[61%]), thrombocytopenia (58 [60%]), and lymphopenia (48 [50%]). Cytokine release syndrome was noted in 92 (95%) of 97 patients (4% as grade 3 or 4); with median time to onset of 7.0 days (IQR 5-8) and median duration of 4.0 days (IQR 3-6). CAR T-cell neurotoxicity was noted in 20 (21%) patients (9% as grade 3 or 4). Fourteen deaths (6 due to treatment-related adverse events, 5 due to progressive disease, and 3 due to treatment-unrelated adverse events) were noted in the study. The investigators concluded that a single cilta-cel infusion at a target dose of 0.75 x 106 CAR-positive viable T cells per kg resulted in early, deep, and durable responses in heavily pretreated patients with multiple myeloma with a reasonable safety profile.

On April 5, 2024, the U.S. Food and Drug Administration (FDA) approved Carvykti (ciltacabtagene autoleucel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. The FDA approval was based on supporting data from the Phase 3 CARTITUDE-4 study (Johnson & Johnson, 2024).

In the Phase 3 CARTITUDE-4 study, a randomized, open-label, multicenter controlled trial, San-Miguel et al. (2023) investigated Carvykti (ciltacabtagene autoleucel) in earlier treatment lines in patients with relapsed and lenalidomide-refractory multiple myeloma, who previously received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. A total of 419 patients underwent a 1:1 randomization to receive either a sequence of apheresis, bridging therapy, lymphodepletion and Carvykti (n=208) or standard therapy which included daratumumab, pomalidomide and dexamethasone (DPd) or bortezomib, pomalidomide and dexamethasone (PVd) selected by physician prior to randomization based on patient’s prior antimyeloma therapy (n=211). All patients received one to three previous lines of treatment. The primary efficacy measure was progression-free survival (PFS). At a median follow-up of 15.9 months, median PFS was 12 months (95% confidence interval [CI]; 9.8, 14) for standard therapy group and not estimable (NE) x(95% CI: 22.8, NE) for Carvykti group (Hazard ratio: 0.41 [95% CI: 0.30, 0.56]). The estimated PFS rate at 12 months was 75.9% (95% CI: 69.4%, 81.1%) in the Carvykti group and 49.5% (95% CI: 42.3%, 56.3%) in the standard therapy group. More patients in the Carvykti group than in the standard therapy group had an overall response (84.6% versus 67.8%), a complete response or better (74% versus 22.3%), and absence of minimal residual disease (60.6% versus 15.6%). The investigators concluded that a single Carvykti infusion resulted in a lower risk of disease progression or death than standard therapy in relapsed or lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies.

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References