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Ciltacabtagene Autoleucel

FDA Drug Information • Also known as: Carvykti

Brand Names
Carvykti
Route
INTRAVENOUS
Dosage Form
INJECTION, SUSPENSION
Product Type
CELLULAR THERAPY

⚠ Boxed Warning (Black Box)

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI. Do not administer CARVYKTI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.2) ] . Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI. Provide supportive care and/or corticosteroids as needed [see Dosage and Administration (2.2 , 2.3) , Warnings and Precautions (5.3) ] . Parkinsonism and Guillain-Barré syndrome (GBS) and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI [see Warnings and Precautions (5.3) ] . Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI. HLH/MAS can occur with CRS or neurologic toxicities [see Warnings and Precautions (5.4) ]. Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI [see Warnings and Precautions (5.5) ] . Immune Effector Cell-associated Enterocolitis (IEC-EC), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI [see Warnings and Precautions (5.9) ]. Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred in patients following treatment with CARVYKTI. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI [see Warnings and Precautions (5.10) ] . WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES See full prescribing information for complete boxed warning. Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI. Do not administer CARVYKTI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. ( 2.2 , 2.3 , 5.2 ) Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI. Provide supportive care and/or corticosteroids as needed. ( 2.2 , 2.3 , 5.3 ) Parkinsonism and Guillain-Barré syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI. ( 5.3 ) Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI. HLH/MAS can occur with CRS or neurologic toxicities. ( 5.4 ) Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI. ( 5.5 ) Immune Effector Cell-associated Enterocolitis (IEC-EC), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI. ( 5.9 ) Secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, have occurred following treatment with CARVYKTI. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI. ( 5.10 )

Description

11 DESCRIPTION CARVYKTI ® (ciltacabtagene autoleucel) is a BCMA-directed genetically modified autologous T cell immunotherapy. CARVYKTI is prepared from the patient's peripheral blood mononuclear cells, which are obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells and genetically modified ex vivo by transduction with a replication-incompetent lentiviral vector to express a CAR comprising an anti-BCMA targeting domain, which consists of two single-domain antibodies linked to a 4-1BB costimulatory domain and a CD3-zeta signaling domain. The transduced anti-BCMA CAR T cells are expanded in cell culture, washed, formulated into a suspension and cryopreserved. The product must pass a sterility test before release for shipping as a frozen suspension in a patient-specific infusion bag. The product is thawed and then infused back into the patient, where the anti-BCMA CAR T cells can recognize and eliminate BCMA-expressing target cells [see Dosage and Administration (2.2) , How Supplied/Storage and Handling (16) ]. In addition to T cells, CARVYKTI may contain Natural Killer (NK) cells. The formulation contains 5% dimethyl sulfoxide (DMSO).

What Is Ciltacabtagene Autoleucel Used For?

1 INDICATIONS AND USAGE 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. CARVYKTI is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy 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. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For autologous use only. For intravenous use only. Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of CARVYKTI. ( 2.2 ) Do NOT use a leukodepleting filter. ( 2.2 ) Verify the patient's identity prior to infusion. ( 2.2 ) Premedicate with acetaminophen and an H1-antihistamine. ( 2.2 ) Avoid prophylactic use of systemic corticosteroids. ( 2.2 ) Confirm availability of tocilizumab prior to infusion. ( 2.2 , 5.2 ) Dosing of CARVYKTI is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. ( 2.1 ) Recommended dose range is 0.5–1.0×10 6 CAR-positive viable T cells per kg of body weight, with a maximum dose of 1×10 8 CAR-positive viable T cells per single-dose infusion. ( 2.1 ) 2.1 Dose CARVYKTI is provided as a single dose for infusion containing a suspension of chimeric antigen receptor (CAR)-positive viable T cells in one infusion bag. The recommended dose range is 0.5–1.0×10 6 CAR-positive viable T cells per kg of body weight, with a maximum dose of 1×10 8 CAR-positive viable T cells per single infusion. 2.2 Administration CARVYKTI is for autologous use only. For intravenous use only. The patient's identity must match the patient identifiers on the CARVYKTI cassette and infusion bag. Do not infuse CARVYKTI if the information on the patient-specific labels does not match the intended patient. Preparing the Patient for CARVYKTI Infusion Confirm availability of CARVYKTI prior to starting the lymphodepleting chemotherapy regimen. Pretreatment Administer the lymphodepleting chemotherapy regimen: cyclophosphamide 300 mg/m 2 intravenously (IV) and fludarabine 30 mg/m 2 IV daily for 3 days. See the prescribing information of cyclophosphamide and fludarabine for information on dose adjustment in renal impairment. Lymphodepleting regimen must be delayed if a patient has serious adverse reactions from preceding bridging therapies (including clinically significant active infection, cardiac toxicity, and pulmonary toxicity) or active graft versus host disease in patient with prior allogeneic stem cell transplant. Consider repeating lymphodepleting regimen if CARVYKTI dosing is delayed by more than 14 days and patient has recovered from toxicity of the first lymphodepleting regimen. Administer CARVYKTI infusion 2 to 4 days after the completion of the lymphodepleting chemotherapy regimen. CARVYKTI infusion should be delayed if a patient has any of the following conditions: Clinically significant active infection or inflammatory disorders. Grade ≥3 non-hematologic toxicities of cyclophosphamide and fludarabine conditioning, except for Grade 3 nausea, vomiting, diarrhea, or constipation. CARVYKTI infusion should be delayed until resolution of these events to Grade ≤1. Premedication Administer the following pre-infusion medications to all patients 30 – 60 minutes prior to CARVYKTI infusion: Antipyretics (oral or intravenous acetaminophen 650 to 1000 mg). Antihistamine...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common nonlaboratory adverse reactions (incidence greater than 20%) are 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. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described in the WARNINGS and PRECAUTIONS section reflect exposure to CARVYKTI in 285 patients with relapsed or refractory multiple myeloma: one randomized, open-label with 188 patients in CARTITUDE-4 and one single-arm, open-label study with 97 patients in CARTITUDE-1. CARTITUDE-4 The safety of CARVYKTI was evaluated in CARTITUDE-4, a randomized, open-label multicenter study, in which patients with relapsed and lenalidomide refractory multiple myeloma received CARVYKTI meeting the product specifications (N=188) or standard therapy (N=211) [see Clinical Studies (14) ] . Patients with known active or prior history of central nervous system involvement, patients who exhibit clinical signs of meningeal involvement of multiple myeloma and patients with a history of Parkinson's disease or other neurodegenerative disorder, were excluded from the trial. Patients received CARVYKTI at a median dose of 0.71×10 6 CAR-positive viable T-cells/kg (range: 0.41 to 1.08×10 6 cells/kg). The median age of the 188 participants was 62 years (range: 27 to 78 years); 40% were 65 years or older, and 57% were male; 76% were White, were 9% Hispanic or Latino, 8% were Asian, and 3% were Black. The Eastern Cooperative Oncology Group (ECOG) performance status at baseline was 0 in 56%, 1 in 44%. For the details about the study population, see Clinical Studies (14) . The most common nonlaboratory adverse reactions (≥20%) included pyrexia, CRS, hypogammaglobulinemia, musculoskeletal pain, fatigue, upper respiratory tract infection, diarrhea, viral infections, headache, hypotension, and nausea. Serious adverse reactions occurred in 34% of patients. The most common nonlaboratory serious adverse reactions (≥5%) were pneumonia (9%), viral infection (6%), CRS (6%), and cranial nerve palsies (5%). Table 3 summarizes the adverse reactions that occurred in at least 10% of patients treated with CARVYKTI. Table 3: Adverse reactions observed in at least 10% of patients treated with CARVYKTI (N=188) and standard therapy (N=208) in CARTITUDE-4 CARVYKTI N=188 CARVYKTI N=188 Standard Therapy N=208 Standard Therapy N=208 System Organ Class (SOC) Preferred term Any Grade (%) Grade 3 or higher (%) Any Grade (%) Grade 3 or higher (%) Gastrointestinal disorders - - - - Diarrhea Diarrhea includes Colitis, and Diarrhea. 27 3 27 2 Nausea 20 0 18 1 Constipation 10 0 21 1 General disorders and administrative site conditions - - - - Pyrexia 79 5 16 1 Fatigue Represents multiple related terms. 28 3 50 3 Edema Edema includes Face edema, Generalized edema, Localized edema, Edema peripheral, Periorbital edema, Peripheral swelling, Pulmonary edema, and Scrotal edema. 11 1 20 1 Pain 10 1 14 <1 Immune system disorders - - - - Hypogammaglobulinemia Hypogammaglobulinemia includes subjects with adverse event of hypogammaglobulinemia and/or laboratory IgG levels that fell below 500 mg/dL following...

Drug Interactions

7 DRUG INTERACTIONS HIV and the lentivirus used to make CARVYKTI have limited, short spans of identical genetic material (RNA). Therefore, some commercial HIV nucleic acid tests (NATs) may yield false-positive results in patients who have received CARVYKTI.

Contraindications

4 CONTRAINDICATIONS None. None ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on the use of CARVYKTI in pregnant women. No reproductive and developmental toxicity studies in animals have been conducted with CARVYKTI to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether CARVYKTI has the potential to be transferred to the fetus and cause fetal toxicity. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including B-cell lymphocytopenia and hypogammaglobulinemia. Therefore, CARVYKTI is not recommended for women who are pregnant, or for women of childbearing potential not using contraception. Pregnant women should be advised that there may be risks to the fetus. Pregnancy after CARVYKTI therapy should be discussed with the treating physician. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING CARVYKTI ® is supplied in one infusion bag containing a frozen suspension of genetically modified autologous T cells in 5% DMSO, either as a: 70 mL suspension in an infusion bag and metal cassette (NDC 57894-111-01) or 30 mL suspension in an infusion bag and metal cassette (NDC 57894-111-02) Each CARVYKTI infusion bag is individually packed in an aluminum cryo-cassette. Match the identity of the patient with the patient identifiers on the cassette and infusion bag upon receipt. Store and transport below -120 °C, e.g., in a container for cryogenic storage in the vapor phase of liquid nitrogen. Store CARVYKTI in the original packaging containing the cassette protecting the infusion bag. Thaw CARVYKTI prior to infusion [see Dosage and Administration (2) ] .

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.