Idecabtagene Vicleucel (Monograph)

Brand name: Abecma
Drug class: Gene Therapy

Medically reviewed by Drugs.com on Dec 17, 2023. Written by ASHP.

Introduction

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

Uses for Idecabtagene Vicleucel

Idecabtagene vicleucel has the following uses:

Idecabtagene vicleucel 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 an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Idecabtagene vicleucel has been designated an orphan drug by FDA for this use.

Idecabtagene vicleucel is an individualized cellular product prepared from autologous T cells obtained by leukopheresis. The patient's T-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 and safety of idecabtagene vicleucel were evaluated in a single arm, open-label, multicenter study (KarMMa study) in patients with relapsed or refractory multiple myeloma who received ≥3 prior lines of therapy. Patients received lymphodepleting chemotherapy (cyclophosphamide and fludarabine), followed by a single IV infusion of idecabtagene vicleucel, In the efficacy population of 100 patients, the overall response rate was 72% and the stringent complete response (CR) rate was 28%. Of the 72 subjects who achieved an objective response, the median duration of response was 11 months. At a median follow up of 10.7 months, the median duration of response for stringent CR was 19 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

Tecvayli, Revlimid, Darzalex, Velcade, Pomalyst, Kyprolis, Ninlaro

Idecabtagene Vicleucel Dosage and Administration

General

Idecabtagene vicleucel is available in the following dosage form(s) and strength(s):

• Idecabtagene vicleucel is a cell suspension for IV infusion.

• A single dose of idecabtagene vicleucel contains a cell suspension of 300 to 460 × 10⁶ CAR-positive T cells in one or more infusion bags.

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 idecabtagene vicleucel at a certified healthcare facility.

• Do NOT use a leukodepleting filter.

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

• Confirm the patient's identity prior to infusion. Check that the patient's identity matches patient identifiers on the idecabtagene vicleucel cassette(s) and infusion bag(s). Do not infuse idecabtagene vicleucel if the information on the patient-specific label(s) does not match the intended patient.

• Premedicate with acetaminophen and an H₁-antihistamine approximately 30 to 60 minutes before infusion.

• Avoid prophylactic use of dexamethasone or other systemic corticosteroids as such use may interfere with the activity of idecabtagene vicleucel.

• Confirm availability of tocilizumab prior to infusion.

• Dosing of idecabtagene vicleucel is based on the number of chimeric antigen receptor (CAR)-positive T cells. The recommended dose range is 300 to 460 × 10⁶ CAR-positive T cells.

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

Cautions for Idecabtagene Vicleucel

Contraindications

None.

Warnings/Precautions

Cytokine Release Syndrome

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with idecabtagene vicleucel. CRS occurred in 85% (108/127) of patients receiving idecabtagene vicleucel. Grade 3 or higher CRS (Lee grading system) occurred in 9% (12/127) of patients, with Grade 5 CRS reported in one (0.8%) patient. The median time-to-onset of CRS, any grade, was 1 day (range: 1 to 23 days), and the median duration of CRS was 7 days (range: 1 to 63 days) in all patients, including the patient who died. The most common manifestations of CRS included pyrexia (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, ARDS, atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, multiple organ dysfunction syndrome and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

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 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.

Overall rate of CRS was 79%, and rate of Grade 2 CRS was 23% in patients treated in the 300 × 10⁶CAR-positive T cells dose cohort (dose ranging from 277 to 339 × 10⁶CAR-positive T cells). For patients treated in the 450 × 10⁶CAR-positive T cells dose cohort (dose range 447 to 518 × 10⁶CAR-positive T cells), the overall rate of CRS was 96%, and rate of Grade 2 CRS was 40%. Rate of Grade 3 or higher CRS was similar across the dose range. The median duration of CRS for the 450 × 10⁶ CAR-positive T cells dose cohort was 7 days (range 1 to 63 days), and was 6 days (range 2 to 28 days) for the 300 × 10⁶ CAR-positive T cells dose cohort. In the 450 × 10⁶ CAR-positive T cells dose cohort, 68% (36/53) of patients received tocilizumab and 23% (12/53) received at least 1 dose of corticosteroids for treatment of CRS. This was higher than the tocilizumab use of 44% (31/70) and corticosteroid use of 10% (7/70) at the 300 × 10⁶CAR-positive T cells dose cohort.

Sixty-eight of 127 (54%) patients received tocilizumab; 35% (45/127) received a single dose, while 18% (23/127) received more than 1 dose of tocilizumab. Overall, across the dose levels, 15% (19/127) of patients received at least 1 dose of corticosteroids for treatment of CRS. All patients that received corticosteroids for CRS also received tocilizumab.

Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of idecabtagene vicleucel.

Monitor patients at least daily for 7 days following idecabtagene vicleucel infusion at the 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, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated.

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 or life-threatening, occurred following treatment with idecabtagene vicleucel, including concurrently with CRS, after CRS resolution, or in the absence of CRS.

CAR T cell-associated neurotoxicity, occurred in 28% (36/127) of patients receiving idecabtagene vicleucel, including Grade 3 in 4% (5/127) of patients. One patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff. The median time to onset of neurotoxicity was 2 days (range: 1 to 42 days). CAR T cell-associated neurotoxicity resolved in 33 of 36 (92%). For patients who experienced neurotoxicity including 3 patients with ongoing neurotoxicity, the median duration of CAR T cell-associated neurotoxicity was 6 days (range: 1 to 578 days). Neurotoxicity resolved in 33 patients and median time to resolution was 5 days (range 1 to 61 days). Thirty-four patients with neurotoxicity had CRS. The onset of neurotoxicity during CRS was observed in 29 patients, before the onset of CRS in 3 patients, and after the CRS event in 2 patients.

The rate of Grade 3 neurotoxicity was 8% in 450 × 10⁶CAR-positive T cells dose cohort and 1.4% in the 300 × 10⁶CAR-positive T cells dose cohort. The most frequent (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (20%), tremor (9%), aphasia (7%), and delirium (6%).

Grade 4 neurotoxicity and cerebral edema have been associated with idecabtagene vicleucel in a patient in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have occurred after treatment with idecabtagene vicleucel in another study in multiple myeloma.

Monitor patients at least daily for 7 days following idecabtagene vicleucel infusion at the REMS-certified healthcare facility for signs and symptoms of neurologic toxicities. Rule out other causes of neurologic symptoms. Monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

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

Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome

Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) occurred in 4% (5/127) of patients receiving idecabtagene vicleucel. One patient treated in the 300 ×10⁶CAR-positive T cells dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved.

The rate of HLH/MAS was 8% in the 450 ×10⁶CAR-positive T cells dose cohort and 1% in the 300 ×10⁶CAR-positive T cells dose cohort. All events of HLH/MAS had onset within 10 days of receiving idecabtagene vicleucel, with a median onset of 7 days (range: 4 to 9 days) and occurred in the setting of ongoing or worsening CRS. Two patients with HLH/MAS had overlapping neurotoxicity.

The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenia.

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

REMS

Because of the risk of CRS and neurologic toxicities, idecabtagene vicleucel is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the idecabtagene vicleucel REMS.

Healthcare facilities that dispense and administer idecabtagene vicleucel 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 idecabtagene vicleucel infusion, if needed for treatment of CRS. Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer idecabtagene vicleucel are trained in the management of CRS and neurologic toxicities. Further information is available at www.Idecabtagene vicleucelREMS.com or contact Bristol-Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of idecabtagene vicleucel. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in idecabtagene vicleucel.

Infections

Idecabtagene vicleucel should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after idecabtagene vicleucel infusion. Infections (all grades) occurred in 70% of patients. Grade 3 or 4 infections occurred in 23% of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 15%, viral infections in 9%, bacterial infections in 3.9%, and fungal infections in 0.8% of patients. Overall, 4 patients had Grade 5 infections (3%); 2 patients (1.6%) had Grade 5 events of pneumonia, 1 patient (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 patient (0.8%) had cytomegalovirus (CMV) pneumonia associated with pneumocystis jirovecii. Monitor patients for signs and symptoms of infection before and after idecabtagene vicleucel infusion and treat appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to standard institutional guidelines.

Febrile neutropenia was observed in 16% (20/127) of patients after idecabtagene vicleucel 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.

Viral Reactivation

Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following idecabtagene vicleucel administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines.

Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells.

Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing.

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

Prolonged Cytopenias

Patients may exhibit prolonged cytopenias following lymphodepleting chemotherapy and idecabtagene vicleucel infusion. In the KarMMa study, 41% of patients (52/127) experienced prolonged Grade 3 or 4 neutropenia and 49% (62/127) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following idecabtagene vicleucel infusion. Rate of prolonged neutropenia was 49% in the 450 × 10⁶ CAR-positive T cells dose cohort and 34% in the 300 × 10⁶CAR-positive T cells dose cohort. In 83% (43/52) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from idecabtagene vicleucel infusion was 1.9 months. In 65% (40/62) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 2.1 months. Median time to cytopenia recovery was similar across the 300 and 450 × 10⁶ CAR-positive T cells dose cohort.

Three patients underwent stem cell therapy (2 patients with autologous and 1 with allogeneic cells) for hematopoietic reconstitution due to prolonged cytopenia. Two of the three patients died from complications of prolonged cytopenia, which occurred in the setting of ongoing or prior severe CRS or HLH/MAS. Cause of death included lower GI bleeding in the setting of prolonged thrombocytopenia in one patient and bronchopulmonary aspergillosis in the setting of prolonged neutropenia in another patient. The third patient recovered from neutropenia after autologous stem cell therapy.

Monitor blood counts prior to and after idecabtagene vicleucel infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to local institutional guidelines.

Hypogammaglobulinemia

Plasma cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with idecabtagene vicleucel. Hypogammaglobulinemia was reported as an adverse event in 21% (27/127) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 25% (32/127) of patients treated with idecabtagene vicleucel.

Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion occurred in 41% (52/127) of patients treated with idecabtagene vicleucel. Sixty-one percent of patients received IV immunoglobulin (IVIG) post-idecabtagene vicleucel for serum IgG <400 mg/dL.

Monitor immunoglobulin levels after treatment with idecabtagene vicleucel 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 idecabtagene vicleucel 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 idecabtagene vicleucel treatment, and until immune recovery following treatment with idecabtagene vicleucel.

Secondary Malignancies

Patients treated with idecabtagene vicleucel may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1-888-805-4555 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 or seizures, patients receiving idecabtagene vicleucel are at risk for altered or decreased consciousness or coordination in the 8 weeks following treatment. 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.

Specific Populations

Pregnancy

There are no available data with idecabtagene vicleucel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with idecabtagene vicleucel to assess whether it can cause fetal harm when administered to a pregnant woman.

It is not known if idecabtagene vicleucel has the potential to be transferred to the fetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause fetal toxicity, including plasma cell aplasia or hypogammaglobulinemia. Therefore, idecabtagene vicleucel is not recommended for women who are pregnant, and pregnancy after idecabtagene vicleucel infusion should be discussed with the treating physician. Assess immunoglobulin levels in newborns of mothers treated with idecabtagene vicleucel.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Lactation

There is no information regarding the presence of idecabtagene vicleucel 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 idecabtagene vicleucel and any potential adverse effects on the breastfed infant from idecabtagene vicleucel or from the underlying maternal condition.

Females and Males of Reproductive Potential

Pregnancy status of sexually-active females with reproductive potential should be verified via pregnancy testing prior to starting treatment with idecabtagene vicleucel.

See the prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy.

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with idecabtagene vicleucel.

There are no data on the effect of idecabtagene vicleucel on fertility.

Pediatric Use

The safety and efficacy of idecabtagene vicleucel in patients under 18 years of age have not been established.

Geriatric Use

In the clinical trial of idecabtagene vicleucel, 45 (35%) of the 127 patients in the KarMMa study were 65 years of age or older and 4/127 (3%) patients were 75 years of age or older. All five cases of Grade 3 neurotoxicity occurred in patients ≥65 years of age (66 to 74 years). No clinically important differences in effectiveness of idecabtagene vicleucel were observed between these patients and patients younger than 65 years of age.

Common Adverse Effects

The most common non-laboratory adverse reactions (≥20%) include CRS, infections (pathogen unspecified), fatigue, musculoskeletal pain, hypogammaglobulinemia, diarrhea, upper respiratory tract infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased appetite.

The most common laboratory adverse reactions (≥50%) include neutropenia, leukopenia, lymphopenia, 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:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Idecabtagene vicleucel is a chimeric antigen receptor (CAR)-positive T cell therapy targeting B-cell maturation antigen (BCMA), which is expressed on the surface of normal and malignant plasma cells. The CAR construct includes an anti-BCMA scFv-targeting domain for antigen specificity, a transmembrane domain, a CD3-zeta T cell activation domain, and a 4-1BB costimulatory domain. Antigen-specific activation of idecabtagene vicleucel results in CAR-positive T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.

Advice to Patients

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

• Ensure that patients understand the risk of manufacturing failure (1.5%, [2/135 in the clinical study]). In case of a manufacturing failure, a second manufacturing of idecabtagene vicleucel may be attempted. In addition, while the patient awaits the product, additional anticancer treatment (not the lymphodepletion) may be necessary and may increase the risk of adverse events during the pre-infusion period, which could delay or prevent the administration of idecabtagene vicleucel.

• Advise patients to seek immediate attention if Cytokine Release Syndrome (CRS) occurs. Signs or symptoms associated with CRS include fever, hypotension, tachycardia, chills, hypoxia, headache, and fatigue.

• Advise patients to seek immediate attention if neurologic toxicities occur. Signs or symptoms associated with neurologic events include encephalopathy, confusion, seizures, tremor, aphasia, delirium, and somnolence.

• Advise patients to seek immediate attention if signs or symptoms of infection occur.

• Advise patients to seek immediate attention if prolonged cytopenias occur. Signs or symptoms associated with bone marrow suppression include neutropenia, anemia, thrombocytopenia, and febrile neutropenia.

• Advise patients to contact Bristol-Myers Squibb at 1-888-805-4555 if they are diagnosed with a secondary malignancy.

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

• Advise patients of the need to refrain from driving or operating heavy or potentially dangerous machines until at least 8 weeks after idecabtagene vicleucel administration.

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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