Ciltacabtagene Autoleucel (Monograph)

Brand name: Carvykti
Drug class: Gene Therapy

Medically reviewed by Drugs.com on Dec 14, 2023. 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 after 4 or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. 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 is based principally on the results of 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 18 months; 78.4% of patients achieved stringent complete response (sCR), 16.5% 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 21.8 months.

CAR T-cell therapies can be associated with severe toxicities; the American Society of Clinical Oncology (ASCO) has published a guideline to provide guidance on the diagnosis, evaluation and management of such toxicities.

Related/similar drugs

Revlimid, Darzalex, Velcade, Pomalyst, Kyprolis, Ninlaro

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

Cytokine Release Syndrome

Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with ciltacabtagene autoleucel. CRS occurred in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade) occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 1 to 12 days). The median duration of CRS was 4 days (range:1 to 40 days) in all but one patient who had a duration of CRS of 97 days with a subsequent fatal outcome. In patients who experienced CRS, the most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (ALT) (14%), and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation and hemorrhage, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased-C-reactive protein, ferritin, blood alkaline phosphatase, and gamma-glutamyl transferase.

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. One patient with CRS and suspected HLH/MAS developed a fatal retroperitoneal hemorrhage in the setting of thrombocytopenia, coagulopathy and anticoagulation in another ongoing study of ciltacabtagene autoleucel.

Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received tocilizumab without corticosteroids, of whom 33 (34%) received a single dose and 11 (11%) received more than 1 dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids.

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

Monitor patients at least daily for 10 days following ciltacabtagene autoleucel infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 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.

Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel infusion in 26% (25/97) of patients of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in 2 ongoing studies.

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.

ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). Two patients had ongoing Grade 3 and Grade 1 ICANS at last known alive date and one patient had Grade 1 ICANS ongoing at time of death from neurologic toxicity with parkinsonian features. The median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 17 of 22 patients (77%), and the median time to resolution was 6 days (range: 2 to 143 days). Median duration of ICANS in all patients, including those with fatal ICANS, ICANS ongoing at time of death from other causes or ongoing at last known alive date, was 7.5 days (range: 2 to 927 days). All 22 patients with ICANS had CRS. The onset of ICANS occurred during CRS in 16 patients, before the onset of CRS in 3 patients, and after the CRS event in 3 patients.

The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%), and headache (6%).

Monitor patients at least daily for 10 days following ciltacabtagene autoleucel infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

Parkinsonism

Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from ICANS. Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. Symptoms did not respond to one or more of the following treatments attempted in one or more patients – systemic chemotherapy, intrathecal chemotherapy and steroids, dopaminergic agents, systemic corticosteroids, plasmapheresis, and IV immunoglobulin and dasatinib. One patient experienced partial resolution with residual gait disturbance without treatment for parkinsonism, immunosuppressants, or chemotherapy. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range: 15 to 108 days) from infusion of ciltacabtagene autoleucel. One patient died of neurologic toxicity with parkinsonism 247 days after administration of ciltacabtagene autoleucel; two patients with ongoing parkinsonism died of infectious causes 162 and 119 days after administration of ciltacabtagene autoleucel; in the remaining 2 patients, symptoms of parkinsonism were ongoing up to 530 days after administration of ciltacabtagene autoleucel. Maximum toxicity grade was 2, 3, 4 and 5 in 1, 2, 1 and 1 patient respectively. All 5 patients had a history of prior CRS (n=4 Grade 2; n=1 Grade 3), while 4 of 5 patients had prior ICANS (n=4 Grade 1).

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) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with IV immunoglobulins. 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.

Grade 3 myelitis has occurred 25 days following treatment with ciltacabtagene autoleucel in another ongoing study. 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 immune globulin. Myelitis was ongoing at the time of death from other cause.

Peripheral Neuropathy

Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range: 4 to 136 days), median duration of peripheral neuropathies was 256 days (range: 2 to 465 days) including those with ongoing neuropathy. Of these six patients, two patients experienced Grade 3 peripheral neuropathy, and 3 had resolution of neuropathy. Treatment with corticosteroids in one patient was not associated with improvement of peripheral neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel.

Monitor patients for signs and symptoms of peripheral neuropathies.

Cranial Nerve Palsies

Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1. All 3 patients had 7^th cranial nerve palsy; one patient had 5^th cranial nerve palsy as well. Median time to onset was 26 days (range: 21 to 101 days) following infusion of ciltacabtagene autoleucel. All three patients received systemic corticosteroids and had resolution of symptoms; one patient received valacyclovir in addition to corticosteroids. Median time to resolution was 70 days (range: 1 to 79 days) following onset of symptoms. Occurrence of 3^rd and 6^th cranial nerve palsy, bilateral 7^th cranial nerve palsy, worsening of cranial nerve palsy after improvement and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel.

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)

Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel infusion. The HLH event was preceded by prolonged CRS lasting 97 days.

The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia and multi-organ dysfunction, including renal dysfunction.

One patient with grade 4 HLH/MAS developed fatal intracerebral and GI hemorrhage in the setting of coagulopathy and thrombocytopenia 12 days after treatment in another ongoing study of ciltacabtagene autoleucel. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematological parameters in patients with HLH/MAS and transfuse per institutional guidelines.

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.

REMS

Because of the risk of CRS and neurologic toxicities, ciltacabtagene autoleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Carvykti REMS. The required components of the REMS prorgram are:

• Healthcare facilities that dispense and administer ciltacabtagene autoleucel must be enrolled and comply with the REMS requirements.

• Certified healthcare facilities must have on-site, immediate access to tocilizumab.

• Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after ciltacabtagene autoleucel infusion, if needed for treatment of CRS.

• Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense or administer ciltacabtagene autoleucel are trained in the management of CRS and neurologic toxicities.

Further information is available at www.carvyktrems.com or 1-844-672-0067.

Prolonged and Recurrent Cytopenias

Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and ciltacabtagene autoleucel infusion. In Study CARTITUDE-1 (N=97), 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion. In 31% (29/95) of patients who recovered from Grade 3 or 4 neutropenia after 1 month, the median time to recovery from ciltacabtagene autoleucel infusion was 1.8 months (range: 1.0 to 3.7 months). In 52% (32/61) of patients who recovered from Grade 3 or 4 thrombocytopenia after 1 month, the median time to recovery from ciltacabtagene autoleucel infusion was 1.9 months (range: 1.1 to 8.5 months).

One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.

Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia, and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following ciltacabtagene autoleucel infusion. After Day 60 following ciltacabtagene autoleucel, 31%, 12%, and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia, and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty-seven percent (84/97) 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. Six and 11 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.

Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, 4 patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2), and pneumonia (n=1).

Grade 5 infections reported in other studies with ciltacabtagene autoleucel include bronchopulmonary aspergillosis, pneumocystis jirovecii pneumonia, and CMV colitis (with HSV-1 hepatitis). Another patient developed mycotic aneurysm due to cerebral aspergillosis and died of subarachnoid hemorrhage.

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 the 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.

In a randomized controlled study of relapsed or refractory multiple myeloma (CARTITUDE- 4), patients treated with ciltacabtagene autoleucel had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. 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. Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients treated with ciltacabtagene autoleucel. Hypogammaglobulinemia either as an adverse reaction or a laboratory IgG level below 500 mg/dL, after infusion occurred in 94% (91/97) of patients treated with ciltacabtagene autoleucel. Thirty-eight percent 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 in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. All reactions were Grade 1 and symptoms included flushing (n=4), chest discomfort (n=2), tachycardia (n=1), wheezing (n=1), tremor (n=1), and burning sensation (n=1). 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. 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 for testing of secondary malignancy of T cell origin.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline or neuropathy, patients receiving ciltacabtagene autoleucel are at risk for altered or decreased consciousness or coordination in the 8 weeks following ciltacabtagene autoleucel infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities.

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.

Common Adverse Effects

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 laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation and hypoalbuminemia.

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 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 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 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 of signs and symptoms associated with infection.

• Advise patients of the signs and symptoms associated with hypersensitivity reactions including flushing, chest tightness, tachycardia, and difficulty breathing.

• 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 of the need 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 treatment and in the event of any new onset of neurologic toxicities.

• 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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