Ciltacabtagene Autoleucel (Monograph)

Brand name: Carvykti
Drug class: Gene Therapy

Medically reviewed by Drugs.com on Aug 10, 2025. Written by ASHP.

Introduction

Ciltacabtagene autoleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy.

Uses for Ciltacabtagene Autoleucel

Ciltacabtagene autoleucel has the following uses:

Ciltacabtagene autoleucel is a chimeric antigen receptor (CAR) T-cell therapy 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 has been designated an orphan drug by FDA for the treatment of multiple myeloma.

Ciltacabtagene autoleucel is an individualized cellular product prepared from autologous T cells obtained by leukapheresis; the cells are sent to a commercial laboratory where they are genetically modified to express chimeric antigen receptors (CAR) and then infused back into the patient.

Efficacy of ciltacabtagene autoleucel was evaluated in a randomized, open-label, multicenter study (CARTITUDE-4) in adults 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 were randomized to receive either a sequence of apheresis, bridging therapy, lymphodepletion and ciltacabtagene autoleucel or standard therapy, which included daratumumab, pomalidomide and dexamethasone (DPd) or bortezomib, pomalidomide, and dexamethasone (PVd). Patients in the ciltacabtagene autoleucel group received lymphodepleting chemotherapy followed by a single IV infusion of ciltacabtagene autoleucel 5–7 days after the start of lymphodepletion. The primary efficacy measure was progression-free survival (PFS). After a median follow-up of 15.9 months, median PFS was 12 months in the standard therapy group and was not estimable in the ciltacabtagene autoleucel group. The estimated PFS rate at 12 months was 75.9% in the ciltacabtagene autoleucel group and 49.5% in the standard therapy group. Stringent complete response (sCR) was achieved in 65.9% of patients who received ciltacabtagene autoleucel compared with 18% of patients who received standard therapy; 84.6 and 67.8% of patients in these respective treatment groups achieved an overall response.

Efficacy of ciltacabtagene autoleucel was also evaluated in an open-label, single-arm, multicenter trial (CARTITUDE-1) in adults with relapsed or refractory multiple myeloma who previously received at least 3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Patients received a single IV infusion of ciltacabtagene autoleucel 5–7 days after the start of lymphodepletion. In the efficacy population of 97 patients, the overall response rate was 97.9% after a median duration of follow-up of 28 months; 80.4% of patients achieved sCR, 14.4% of patients achieved very good partial response (VGPR), and 3.1% of patients achieved partial response. Of the 95 patients who achieved an overall response, the median duration of response was not estimable.

CAR T-cell therapies can be associated with severe toxicities; the American Society of Clinical Oncology (ASCO) and other experts have published guidelines on the management of these therapies and their associated toxicities.

Ciltacabtagene Autoleucel Dosage and Administration

General

Ciltacabtagene autoleucel is available in the following dosage form(s) and strength(s):

• Cell suspension for IV infusion.

• A single dose of ciltacabtagene autoleucel contains a cell suspension of 0.5–1.0×10⁶ CAR-positive viable T cells per kg body weight in one infusion bag.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

For autologous use only. For IV use only.

• Administer ciltacabtagene autoleucel at a certified healthcare facility.

• Administer a lymphodepleting regimen of cyclophosphamide and fludarabine before infusion of ciltacabtagene autoleucel. Confirm the availability of ciltacabtagene autoleucel prior to starting the lymphodepleting chemotherapy regimen. Administer ciltacabtagene autoleucel 2 to 4 days after completion of lymphodepleting chemotherapy.

• Do NOT use a leukodepleting filter.

• Verify the patient's identity prior to infusion. Check that the patient's identity matches patient identifiers on the ciltacabtagene autoleucel infusion bag. Do not infuse if the information on the patient-specific label does not match the intended patient.

• Premedicate with acetaminophen and an H1-antihistamine 30–60 minutes prior to ciltacabtagene autoleucel infusion.

• Avoid prophylactic use of systemic corticosteroids.

• Confirm availability of tocilizumab prior to infusion.

• Dosing of ciltacabtagene autoleucel is based on the number of chimeric antigen receptor (CAR)-positive viable T cells. The recommended dose range is 0.5–1.0×10⁶ CAR-positive viable T cells per kg of body weight, with a maximum dose of 1×10⁸ CAR-positive viable T cells per single-dose infusion.

• See Full Prescribing Information for detailed instructions on preparation and administration.

Cautions for Ciltacabtagene Autoleucel

Contraindications

None

Warnings/Precautions

Increased Early Mortality

In CARTITUDE-4, a randomized (1:1), controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the ciltacabtagene autoleucel treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the ciltacabtagene autoleucel arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the ciltacabtagene autoleucel arm within the first 10 months of randomization, 10 deaths occurred prior to ciltacabtagene autoleucel infusion, and 19 deaths occurred after the infusion. Of the 10 deaths that occurred prior to ciltacabtagene autoleucel infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after ciltacabtagene autoleucel infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12).

Cytokine Release Syndrome

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with ciltacabtagene autoleucel. Among patients receiving ciltacabtagene autoleucel for relapsed or refractory multiple myeloma in the CARTITUDE-1 and CARTITUDE-4 studies (N=285), CRS occurred in 84% (238/285), including ≥Grade 3 CRS (ASTCT 2019) in 4% (11/285) of patients. The median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). Cytokine release syndrome resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%), and increased aspartate aminotransferase (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia.

Cytokine release syndrome occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4).

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Confirm that a minimum of two doses of tocilizumab are available prior to infusion of ciltacabtagene autoleucel.

Of the 285 patients who received ciltacabtagene autoleucel in clinical trials, 53% (150/285) of patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS.

Monitor patients at least daily for 7 days following ciltacabtagene autoleucel infusion for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 2 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids.

Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic Toxicities

Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with ciltacabtagene autoleucel. Neurologic toxicities included immune effector cell-associated neurotoxicity syndrome (ICANS), neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies for relapsed and refractory multiple myeloma, one or more neurologic toxicities occurred in 24% (69/285), including ≥Grade 3 cases in 7% (19/285) of patients. The median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of patients.

Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS)

Patients receiving ciltacabtagene autoleucel may experience fatal or life-threatening ICANS following treatment with ciltacabtagene autoleucel, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of patients. The median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range: 1 to 143 days). The median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Of patients with ICANS, 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively.

ICANS occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent (≥2%) manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep disorder (2%).

Monitor patients at least daily for 7 days following ciltacabtagene autoleucel infusion for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 2 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Advise patients to avoid driving for at least 2 weeks following infusion.

Parkinsonism

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥3 in 2% (5/285) of patients. The median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) patients with a median time to resolution of 523 days. The median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients.

Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4).

The manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes.

Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson's disease for the improvement or resolution of parkinsonism symptoms following ciltacabtagene autoleucel treatment.

Guillain-Barré Syndrome

A fatal outcome following Guillain-Barré Syndrome (GBS) occurred following treatment with ciltacabtagene autoleucel despite treatment with IV immunoglobulin. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis.

Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS.

Immune Mediated Myelitis

Grade 3 myelitis occurred 25 days following treatment with ciltacabtagene autoleucel in CARTITUDE-4 in a patient who received ciltacabtagene autoleucel as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and IV immunoglobulin. Myelitis was ongoing at the time of death from other cause.

Peripheral Neuropathy

Peripheral neuropathy occurred following treatment with ciltacabtagene autoleucel.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of patients. The median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) patients with a median time to resolution of 58 days (range: 1 to 215 days). The median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cut off.

Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4).

Monitor patients for signs and symptoms of peripheral neuropathies.

Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS.

Cranial Nerve Palsies

Cranial nerve palsies occurred following treatment with ciltacabtagene autoleucel.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of patients. The median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) patients with a median time to resolution of 66 days (range: 1 to 209 days). The median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients including those with ongoing neurologic events at the time of death or data cut off.

Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4).

The most frequent cranial nerve affected was the 7 cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected.

Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS)

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving ciltacabtagene autoleucel, with a median onset of 10 days (range: 8 to 99 days) and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia and multi-organ dysfunction, including renal dysfunction and respiratory failure.

Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with ciltacabtagene autoleucel.

HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.

Prolonged and Recurrent Cytopenias

Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and ciltacabtagene autoleucel infusion.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, Grade 3 or higher cytopenias not resolved by day 30 following ciltacabtagene autoleucel infusion occurred in 62% (176/285) of patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2% (6/285). After Day 60 following ciltacabtagene autoleucel infusion 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.

Monitor blood counts prior to and after ciltacabtagene autoleucel infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.

Infections

Ciltacabtagene autoleucel should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections, occurred in patients after ciltacabtagene autoleucel infusion.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, infections occurred in 57% (163/285), including ≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with ciltacabtagene autoleucel had an increased rate of fatal COVID-19 infections compared to the standard therapy arm.

Monitor patients for signs and symptoms of infection before and after ciltacabtagene autoleucel infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.

Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19.

Viral Reactivation

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia.

Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing.

Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.

Hypogammaglobulinemia

Hypogammaglobulinemia can occur in patients receiving treatment with ciltacabtagene autoleucel.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, a hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 93% (265/285) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL, after infusion occurred in 94% (267/285) of patients treated. Fifty six percent (161/285) of patients received IV immunoglobulin (IVIG) post ciltacabtagene autoleucel for either an adverse reaction or prophylaxis.

Monitor immunoglobulin levels after treatment with ciltacabtagene autoleucel and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Use of Live Vaccines

The safety of immunization with live viral vaccines during or following ciltacabtagene autoleucel treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ciltacabtagene autoleucel treatment, and until immune recovery following treatment with ciltacabtagene autoleucel.

Hypersensitivity Reactions

Hypersensitivity reactions have occurred following treatment with ciltacabtagene autoleucel infusion.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia.

Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in ciltacabtagene autoleucel. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction.

Secondary Malignancies

Patients treated with ciltacabtagene autoleucel may develop secondary malignancies.

Among patients receiving ciltacabtagene autoleucel in the CARTITUDE-1 and CARTITUDE-4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with ciltacabtagene autoleucel. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting.

T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including ciltacabtagene autoleucel. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples.

Specific Populations

Pregnancy

There are no available data on the use of ciltacabtagene autoleucel in pregnant women. No reproductive and developmental toxicity studies in animals have been conducted with ciltacabtagene autoleucel to assess whether it can cause fetal harm when administered to a pregnant woman. It is not known whether ciltacabtagene autoleucel 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, ciltacabtagene autoleucel 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 ciltacabtagene autoleucel 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.

Lactation

There is no information regarding the presence of ciltacabtagene autoleucel in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ciltacabtagene autoleucel and any potential adverse effects on the breastfed infant from ciltacabtagene autoleucel or from the underlying maternal condition.

Females and Males of Reproductive Potential

Pregnancy status for females of child-bearing age should be verified prior to starting treatment with ciltacabtagene autoleucel.

There are insufficient data to provide a recommendation concerning duration of contraception following treatment with ciltacabtagene autoleucel.

In clinical trials, female patients of childbearing potential were advised to practice a highly effective method of contraception and male patients with partners of childbearing potential or whose partners were pregnant were instructed to use a barrier method of contraception, until one year after the patient has received ciltacabtagene autoleucel infusion.

See the prescribing information for lymphodepleting chemotherapy for information on the need for contraception in patients who receive the lymphodepleting chemotherapy.

There are no data on the effect of ciltacabtagene autoleucel on fertility.

Pediatric Use

Safety and effectiveness of ciltacabtagene autoleucel in pediatric patients have not been established.

Geriatric Use

Of the 97 patients in Study CARTITUDE-1 that received ciltacabtagene autoleucel, 28% were 65 to 75 years of age, and 8% were 75 years of age or older. CARTITUDE-1 did not include sufficient numbers of patients 65 years of age and older to determine whether the effectiveness differs compared with that of younger patients. In 62 patients less than 65 years of age, all grade and Grade 3 and higher neurologic toxicities occurred in 19% (12/62) and 6% (4/62) respectively. Of the 35 patients ≥65 years of age, all grade and Grade 3 and higher neurologic toxicities occurred in 37% (13/35) and 20% (7/35), respectively.

Of the 188 patients in CARTITUDE-4 who received ciltacabtagene autoleucel, 38% were 65 to 75 years of age, and 2% were 75 years of age or older. In 112 patients less than 65 years of age, all grade and Grade 3 and higher neurologic toxicities occurred in 16% (18/112) and 3% (3/112), respectively. Of the 76 patients ≥65 years of age, all grade and Grade 3 and higher neurologic toxicities occurred in 34% (26/76) and 7% (5/76), respectively.

Common Adverse Effects

The most common nonlaboratory adverse reactions (incidence >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 ≥50%) include lymphopenia, neutropenia, decreased white blood cell count, thrombocytopenia, and anemia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

HIV and the lentivirus used to make ciltacabtagene autoleucel 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 ciltacabtagene autoleucel.

Actions

Mechanism of Action

Ciltacabtagene autoleucel is a B-cell maturation antigen (BCMA)-directed, genetically modified autologous T cell immunotherapy, which involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. The ciltacabtagene autoleucel CAR protein features two BCMA-targeting single-domain antibodies designed to confer high avidity against human BCMA, a 4-1BB co-stimulatory domain, and a CD3-zeta signaling cytoplasmic domain. Upon binding to BCMA-expressing cells, the CAR promotes T cell activation, expansion, and elimination of target cells.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).

• Inform patients of the risk of manufacturing failure. In case of a manufacturing failure, a second manufacturing of ciltacabtagene autoleucel may be attempted. In addition, while the patient awaits the product, additional anticancer treatment (other than lymphodepletion) may be necessary and may increase the risk of adverse reactions during the pre-infusion period, which could delay or prevent the administration of ciltacabtagene autoleucel.

• Advise patients that they will be monitored daily for the first 7 days following the infusion, and instruct patients to remain within proximity of a healthcare facility for at least 2 weeks following the infusion.

• Inform patients of the risk of early mortality. In a clinical study, treatment in the ciltacabtagene autoleucel arm was associated with a higher rate of death (14%) compared to the control arm (12%) in the first 10 months from randomization. This higher rate of death was observed before receiving ciltacabtagene autoleucel and after treatment. The reasons for death were progression of multiple myeloma and adverse events.

• Advise patients of the signs and symptoms of cytokine release syndrome (CRS), including fever, chills, fatigue, headache, tachycardia, hypotension, hypoxia, dizziness/lightheadedness, and organ toxicities. Advise patients to seek immediate medical attention if signs or symptoms of CRS occur.

• Advise patients of the signs and symptoms associated with neurologic events, some of which occur days, weeks or months following the infusion including immune effector cell-associated neurotoxicity syndrome (ICANS; e.g., aphasia, encephalopathy, depressed level of consciousness, seizures, delirium, dysgraphia), parkinsonism (e.g., tremor, micrographia, bradykinesia, rigidity, shuffling gait, stooped posture, masked facies, apathy, flat affect, lethargy, somnolence), Guillain Barré Syndrome (e.g., motor weakness and polyradiculoneuritis), peripheral neuropathy (e.g., peripheral motor and/or sensory nerve dysfunction), and cranial nerve palsies (e.g., facial paralysis, facial numbness). Advise patients to seek immediate medical attention if signs or symptoms of neurologic toxicity occur.

• Advise patients of the signs and symptoms associated with bone marrow suppression including neutropenia, thrombocytopenia, anemia, or febrile neutropenia for several weeks or months. Signs or symptoms associated with bone marrow suppression may recur. Advise patients to seek immediate medical attention if signs or symptoms of bone marrow suppression occur.

• Advise patients of signs and symptoms associated with infection and to seek immediate medical attention if any such signs and symptoms occur.

• Advise patients of the signs and symptoms associated with hypersensitivity reactions including flushing, chest tightness, tachycardia, and difficulty breathing and to seek immediate medical attention if any such signs and symptoms occur.

• Advise patients of the need to have periodic monitoring of blood counts before and after ciltacabtagene autoleucel infusion.

• Advise patients to contact Janssen Biotech, Inc. at 1-800-526-7736 if they are diagnosed with a secondary malignancy.

• Advise patients to avoid driving for at least 2 weeks.

• Advise patients of the need to tell their physician about their treatment with ciltacabtagene autoleucel before receiving a live virus vaccine.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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