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

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).

Per the prescribing information, ciltacabtagene autoleucel (Carvykti) carries the following black box warnings:

Additional warnings and precautions include prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies, 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.

: 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), call 1-877-212-8811. For Statement of Medical Necessity (SMN) precertification forms, see

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

of the following criteria are met:

The member has received prior treatment with at least four prior lines of therapy, including at least one drug from

of the following categories:

Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational and Background sections).

Continuation of Therapy

See Dosage and Administration information.

Dosage and Administration

Ciltacabtagene autoleucel (Carvykti) is a cell suspension for autologous and intravenous use only administered at a certified healthcare facility. A single dose of Carvykti contains a cell suspension of 0.5 to 1.0 x 10

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 10

CAR-positive viable T cells per kg of body weight, with a maximum dose of 1 x 10

CAR-positive viable T cells per single infusion.

Source: Janssen Biotech, 2022

Experimental and Investigational

Aetna considers ciltacabtagene autoleucel experimental and investigational for the treatment of solid tumors.