Idecabtagene vicleucel is a chimeric antigen receptor (CAR) T-cell gene therapy. It is B-cell maturation antigen (BCMA)-directed immunotherapy that works by using a patient's own genetically altered immune cells to kill BCMA-expressing cancer cells in the blood. Idecabtagene vicleucel is indicated for use in adult patients with relapsed or refractory multiple myeloma who have received 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Cytokine release syndrome and severe neurotoxicity have been reported. Idecabtagene vicleucel is available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Information for this program enrollment is available at www.AbecmaREMS.com or 1-888-423-5436.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Idecabtagene vicleucel may carry the risk of transmitting infectious diseases to health care professionals handling the product. Follow universal precautions and local biosafety guidelines in the handling and disposal of idecabtagene vicleucel.
Route-Specific Administration
Injectable Administration
Visually inspect the contents of the infusion bag(s) for any breaks or cracks before thawing. Do not infuse the contents if the bag is compromised; call Bristol-Myers Squibb at 1-888-805-4555.
Intravenous Administration
-Idecabtagene vicleucel is for autologous and intravenous use.
-The dose of idecabtagene vicleucel may be contained in 1 or more patient-specific infusion bags; verify the number of infusion bags prior to preparation for infusion.
-Ensure tocilizumab and emergency equipment are available prior to the infusion and during the recovery period.
-Coordinate the timing of the idecabtagene vicleucel thaw and infusion; confirm the infusion time in advance and adjust the start time for thaw so that the recipient will be ready.
-Premedicate patients with acetaminophen and diphenhydramine (or another H1-antihistamine) approximately 30 to 60 minutes prior to the infusion; avoid systemic corticosteroids use except in the case of a life-threatening emergency.
Preparation
-Match the patient's identity with the patient identifiers on the cassette; do not remove the product bag from the cassette if the patient-specific label does not match the intended recipient.
-Remove the product bag from the cassette; verify that the patient information on the cassette label matches the bag label.
-If more than 1 infusion bag is part of the treatment dose, thaw each infusion bag one at a time; do not start to thaw the next bag until the previous bag has been infused.
-Put the infusion bag(s) inside a second, sterile bag.
-Thaw the infusion bag(s) at approximately 37 degrees Celsius (C) using an approved thaw device or water bath.
-Once there is no visible ice in the infusion bag, gently mix the contents of the bag to allow the clumps of cellular material to disperse.
-If visible cell clumps remain, continue to gently mix the contents of the bag; small clumps of cellular material should disperse with gentle manual mixing.
-Do not wash, spin down, and/or resuspend idecabtagene vicleucel in new media prior to infusion.
-Storage: Give idecabtagene vicleucel within 1 hour of the start of the thaw. The product may be stored at room temperature for up to 2 hours once thawed.
Intravenous (IV) Infusion
-Confirm the patient's identity with the patient identifiers on the infusion bag.
-Consider administering infusion bag(s) via central venous access, particularly for patients with poor peripheral access.
-Prime the tubing with normal saline prior to the infusion; do not use a leukocyte-depleting filter.
-Administer as an IV infusion within 1 hour from the start of the thaw via gravity flow until the infusion bag is empty.
-Rinse the tubing with 30 to 60 mL of normal saline at the same infusion rate to ensure all product contents are delivered.
-Repeat steps for each infusion bag.
General physical health deterioration was reported in 11% (grade 3 or 4, 10%) of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Tachycardia including sinus tachycardia (19%), hypotension including orthostatic hypotension (17%), hypertension (11%; grade 3 or higher, 3.1%), atrial fibrillation (4.7%), and cardiomyopathy (1.6%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Fatigue occurred in 45% (grade 3 or higher, 3.1%) of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term fatigue included asthenia and malaise.
Fever (25%; grade 3 or higher, 1.6%) and chills (11%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Edema occurred in 25% of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term edema included swelling, face edema, fluid overload, fluid retention, generalized edema, peripheral edema, peripheral swelling, and scrotal/testicular swelling.
Weight loss occurred in 13% (grade 3 or higher, 1.6%) of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Musculoskeletal pain (45%; grade 3 or higher, 3.1%) and motor dysfunction (11%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term musculoskeletal pain included arthralgia, back pain, bone pain including neck and spinal pain, musculoskeletal chest pain, musculoskeletal discomfort/stiffness, and myalgia; the term motor dysfunction included dysphonia, eyelid ptosis, hypotonia, muscle cramps/spasms, muscular weakness, and restless legs syndrome (RLS).
Anxiety (12%; grade 3 or higher, 0.8%), insomnia (13%), and delirium including hallucinations (6%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Renal failure occurred in 10% (grade 3 or higher, 2.4%) of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term renal failure included kidney injury, increased blood creatinine level, chronic kidney disease, and renal impairment.
Dyspnea including respiratory failure (13%; grade 3 or higher, 2.4%), cough including upper-airway cough syndrome (23%), hypoxia (2.4%), and pulmonary edema (2.4%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Rash (14%; grade 3 or higher, 0.8%) and xerosis (11%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term rash included acne vulgaris, bullous rash/dermatitis, erythema, macular rash, papular rash, and urticaria; the term xerosis included xerostomia and xerophthalmia.
Serious infection and hypogammaglobulinemia have been reported with idecabtagene vicleucel therapy. Monitor immunoglobulin levels after idecabtagene vicleucel therapy and administer immunoglobulin (IVIG) replacement for IgG less than 400 mg/dL; also, manage immunoglobulin deficiency with infection precautions and prophylactic antibiotic or antiviral therapy per standard guidelines. Monitor patients for signs and symptoms of infection prior to and after the idecabtagene vicleucel infusion and treat appropriately; administer prophylactic anti-infective therapy as medically indicated. Monitor for CMV reactivation after idecabtagene vicleucel therapy; treat CMV infection per clinical guidelines. Consider antiviral therapy to prevent viral reactivation. Hypogammaglobulinemia (41%; grade 3 or higher, 0.8%) and infection (70%; grade 3 or higher, 23%) including pathogen unspecified infection (51%; grade 3 or higher, 15%), viral infection (27%; grade 3 or higher, 9%), bacterial infection (15%; grade 3 or higher, 3.9%), pneumonia (17%; grade 3 or higher, 9%), upper respiratory tract infection (34%; grade 3 or higher, 1.6%), fungal infection (8%; grade 3 or higher, 0.8%), and sepsis (9%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). In this trial, 3% of patients died due to infectious causes including 2 patients (1.6%) with pneumonia, 1 patient (0.8%) with bronchopulmonary aspergillosis, and 1 patient (0.8%) with cytomegalovirus (CMV) pneumonia associated with Pneumocystis jirovecii. The term upper respiratory tract infection included laryngitis, pharyngitis/nasopharyngitis, pharyngeal erythema, respiratory tract congestion, rhinitis, and sinusitis. The term hypogammaglobulinemia included decreased blood immunoglobulin G level and laboratory IgG levels less than 500 mg/dL.
Grade 3 or 4 elevated hepatic enzymes (e.g., increased ALT, AST, and alkaline phosphatase levels), hypoalbuminemia, and hyperbilirubinemia were each reported in less than 10% of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Grade 3 or 4 hyperglycemia occurred in less than 10% of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Cytokine release syndrome (CRS) was reported in 85% (grade 3 or higher, 9%) of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). One patient had a fatal CRS event. Common symptoms of CRS include fever (98%), hypotension (41%), tachycardia (35%), chills (31%), hypoxia (20%), fatigue (12%), and headache (10%). Serious events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory distress syndrome (ARDS), atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, and multiple organ dysfunction syndrome. Observe patients closely for signs or symptoms of CRS at least daily for 7 days in a certified healthcare facility following the infusion and continue monitoring for at least 4 weeks after the infusion. Evaluate for and treat other causes of fever, hypoxia, and hypotension. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids; CRS refractory to first-line interventions may require alternative treatments such as higher dose corticosteroids, anti-cytokine agents, or anti-T-cell therapies. Monitor patients with CRS (e.g., hypotension not responsive to fluids or hypoxia requiring supplemental oxygenation) with continuous cardiac telemetry and pulse oximetry. Consider starting a non-sedating anti-seizure medication (e.g., levetiracetam) for seizure prophylaxis. Intensive care supportive therapy may be required in patients who have severe or life-threatening CRS.
Neurologic toxicity was reported in patients who received idecabtagene vicleucel therapy. Observe patients closely for signs or symptoms of neurotoxicity at least daily for 7 days in a certified healthcare facility following the infusion and continue monitoring for at least 4 weeks after the infusion. Exclude other causes of neurologic symptoms. Administer supportive care and/or corticosteroids as indicated. Monitor patients with for signs and symptoms of neurotoxicity. Start a non-sedating, anti-seizure medicine (e.g., levetiracetam) for seizure prophylaxis in patients who develop any grade neurotoxicity. Provide intensive care supportive therapy in patients who develop severe or life-threatening neurologic toxicities. Neurotoxicity (28%; grade 3 or higher, 4%), specifically encephalopathy (26%; grade 3 or higher, 6%), headache (23%), dizziness including syncope and vertigo (17%; grade 3 or higher, 0.8%), peripheral neuropathy (17%; grade 3 or higher, 0.8%), tremor including asterixis (10%), aphasia including dysarthria (7%), delirium (6%), ataxia including gait disturbance and Romberg test positive (3.1%), paresis including cranial nerve disorder and hemiparesis (2.4%), and seizures (1.6%), occurred in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). Neurotoxicity developed during cytokine release syndrome (CRS) in 29 patients, prior to the onset of CRS in 3 patients, and after CRS in 2 patients. The incidence of grade 3 neurotoxicity increased with higher CAR-positive T cell doses (450 x 106 CAR-positive T-cells, 8%; 300 x 106 CAR-positive T-cells, 1.4%). Grade 4 neurotoxicity, cerebral edema, grade 3 myelitis and grade 3 parkinsonism were reported following idecabtagene vicleucel therapy in multiple myeloma patients in another study. The term encephalopathy included amnesia, bradyphrenia, cognitive disorder/impaired cognition, confusion, depressed level of consciousness, disturbance in attention, dyscalculia, dysgraphia, lethargy, memory impairment, mental status changes, somnolence/drowsiness, and toxic encephalopathy. The term peripheral neuropathy included carpal tunnel syndrome, hypoesthesia, neuralgia, neuropathy peripheral, paresthesias, and sciatica.
Thrombosis including deep vein thrombosis, jugular vein thrombosis, portal vein thrombosis, and pulmonary embolism occurred in 3.1% of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127).
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) was reported in 4% of patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). Symptoms of HLH/MAS may include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenias. HLH/MAS may occur concurrently with neurotoxicity or cytokine release syndrome (CRS). The incidence of HLH/MAS increased with higher CAR-positive T cell doses (450 x 106 CAR-positive T-cells, 8%; 300 x 106 CAR-positive T-cells, 1%). HLH/MAS may occur concurrently with neurotoxicity or cytokine release syndrome (CRS). One case of fatal multi-organ HLH/MAS with CRS occurred in a patient who received 300 x 106 CAR-positive T-cells. Additionally, HLH/MAS contributed to a fatal case of bronchopulmonary aspergillosis. Evaluate for HLH/MAS in patients with progressive symptoms of CRS or refractory CRS despite first-line treatment. Treat patients with HLH/MAS per institutional standards.
Grade 3 or 4 bone marrow suppression/cytopenias not resolved by 1 month have been reported in patients following lymphodepleting chemotherapy and idecabtagene vicleucel; prolonged grade 3 or 4 cytopenias included thrombocytopenia (49%) and neutropenia (41%). Monitor complete blood counts prior to and after the idecabtagene vicleucel infusion. Provide myeloid growth factor and blood product transfusion support according to institutional guidelines. Grade 3 or 4 lymphopenia (92%), leukopenia (96%), neutropenia (96%), anemia (63%), and thrombocytopenia (63%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). Additionally, grade 3 or higher febrile neutropenia was reported following idecabtagene vicleucel therapy in 16% of patients; it sometimes occurred concurrently with cytokine release syndrome. If a patient develops febrile neutropenia, evaluate for signs of infection and manage with broad spectrum antibiotics and supportive care therapy (e.g., fluids) as medically indicated. Two patients who underwent stem-cell therapy (1 with autologous and 1 with allogeneic cells) for hematopoietic reconstitution due to prolonged cytopenia died; death was attributed to lower gastrointestinal bleeding in the setting of prolonged thrombocytopenia in one patient and bronchopulmonary aspergillosis in the setting of prolonged neutropenia in another patient. A third patient recovered from neutropenia after autologous stem-cell therapy.
Gastrointestinal (GI) toxicity including diarrhea (35%; grade 3 or higher, 1.6%), nausea (29%), decreased appetite/anorexia (22%; grade 3 or higher, 0.8%), constipation (16%), vomiting (15%), oral pain including dental pain (12%), and GI bleeding (3.1%) were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term GI bleeding included hemorrhoidal bleeding and melena.
Coagulopathy (9%), grade 3 or 4 hypofibrinogenemia (less than 10%), and grade 3 or 4 prolonged activated partial thromboplastin time (aPTT) (10%) that worsened from baseline were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). The term coagulopathy included prolonged bleeding time (prolonged aPTT), supratherapeutic anticoagulation drug level, disseminated intravascular coagulation (DIC), and increased international normalized ratio (INR).
Grade 3 or 4 hypophosphatemia (45%) and hyponatremia (10%) that worsened from baseline were reported in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel in a nonrandomized trial (n = 127). Additionally, grade 3 or 4 hypokalemia and hypocalcemia occurred in less than 10% of patients.
Antibody formation to CAR T-cells occurred in 3% of patients prior to and 47% of patients after the idecabtagene vicleucel infusion in a nonrandomized trial (n = 127). There is no evidence that the presence of these antibodies had an impact on cellular expansion or on the effectiveness or safety of idecabtagene vicleucel.
T-cell malignancies, including chimeric antigen receptor (CAR)-positive lymphoma, have been reported in patients who received treatment with B-cell maturation antigen (BCMA)-directed autologous CAR T-cell immunotherapy in clinical trials and postmarketing surveillance. If a patient develops a new primary malignancy following treatment with idecabtagene vicleucel, contact Bristol-Myers Squibb at 1-888-805-4555 for instructions on how to collect patient samples for testing for the presence of the CAR transgene. Report suspected adverse events, including T-cell malignancies, to the FDA.
Cytokine release syndrome (CRS) has been reported with idecabtagene vicleucel; some cases were fatal or life-threatening. Confirm that 2 tocilizumab doses are available at the facility site prior to the idecabtagene vicleucel infusion. Observe patients closely for signs or symptoms of CRS at least daily for 7 days in a certified healthcare facility following the infusion and continue monitoring for at least 4 weeks after the infusion. Evaluate for and treat other causes of fever, hypoxia, and hypotension. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids; CRS refractory to first-line interventions may require alternative treatments such as higher dose corticosteroids, anti-cytokine agents, or anti-T-cell therapies. Monitor patients with severe CRS (e.g., hypotension not responsive to fluids or hypoxia requiring supplemental oxygenation) with continuous cardiac telemetry and pulse oximetry. Consider starting a non-sedating anti-seizure medication (e.g., levetiracetam) for seizure prophylaxis. Intensive care supportive therapy may be required in patients who have severe or life-threatening CRS.
Severe neurotoxicity (e.g., encephalopathy, myelitis, and cerebral edema) has been reported with idecabtagene vicleucel therapy; some cases were fatal or life-threatening. Geriatric patients (aged 65 years or older) may be at increased risk of developing severe neurotoxicity. Neurologic toxicity may occur concurrently with cytokine release syndrome (CRS) or after CRS resolves. Advise patients to avoid driving or operating machinery or performing other dangerous duties for 8 weeks after the idecabtagene vicleucel infusion due to the risk of neurologic events (e.g., mental status changes, seizures) and altered or decreased consciousness or coordination. Observe patients closely for signs or symptoms of neurotoxicity at least daily for 7 days in a certified healthcare facility following the infusion and continue monitoring for at least 4 weeks after the infusion. Exclude other causes of neurologic symptoms. Administer supportive care and/or corticosteroids as indicated. Monitor patients with for signs and symptoms of neurotoxicity. Start a non-sedating, anti-seizure medicine (e.g., levetiracetam) for seizure prophylaxis in patients who develop any grade neurotoxicity. Provide intensive care supportive therapy in patients who develop severe or life-threatening neurologic toxicities.
Hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) has been reported with idecabtagene vicleucel therapy; some cases were fatal or life-threatening. Symptoms of HLH/MAS may include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction, and cytopenias. HLH/MAS may occur concurrently with neurotoxicity or cytokine release syndrome (CRS). Evaluate for HLH/MAS in patients with progressive symptoms of CRS or refractory CRS despite first-line treatment. Treat patients with HLH/MAS per institutional guidelines. Hypersensitivity reactions including anaphylaxis may occur with idecabtagene vicleucel therapy; reactions may be due to dimethyl sulfoxide (DMSO) in the product. Therefore, premedicate patients with acetaminophen and diphenhydramine prior to the idecabtagene vicleucel infusion. Monitor patients for signs or symptoms of hypersensitivity during the idecabtagene vicleucel infusion.
Because of the risk of cytokine release syndrome and neurological toxicities, use requires an experienced clinician with training in the management of these toxicities. Idecabtagene vicleucel administration also requires a specialized care setting that is enrolled in the ABECMA REMS program and can comply with all program requirements (e.g., 2 doses of tocilizumab are available for each patient within 2 hours of the idecabtagene vicleucel infusion).
Vaccination with live viral vaccines during or following treatment with idecabtagene vicleucel has not been studied. Live virus vaccination is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and until immune recovery after idecabtagene vicleucel therapy.
Do not administer idecabtagene vicleucel in patients with active infection or inflammation disorders. Serious infections including bacterial infection, fungal infection, viral infection, and opportunistic infections have been reported with idecabtagene vicleucel therapy; some cases were life-threatening or fatal. Monitor patients for signs and symptoms of infection prior to and after the idecabtagene vicleucel infusion and treat appropriately; administer prophylactic anti-infective therapy as medically indicated. Febrile neutropenia has also been reported following idecabtagene vicleucel therapy; it may occur concurrently with cytokine release syndrome. If a patient develops febrile neutropenia, evaluate for signs of infection and manage with broad spectrum antibiotics and supportive care therapy (e.g., fluids) as medically indicated.
Prolonged bone marrow suppression/cytopenias (e.g., neutropenia and thrombocytopenia) resulting in bleeding or infection have been reported following idecabtagene vicleucel therapy; fatal complications due to prolonged cytopenias have also occurred. Monitor complete blood counts prior to and after the idecabtagene vicleucel infusion. Provide myeloid growth factor and blood product transfusion support according to institutional guidelines.
Due to the risk of a new primary malignancy, including T-cell malignancies, life-long monitoring is recommended following idecabtagene vicleucel therapy.
Hypogammaglobulinemia and plasma-cell aplasia may occur with idecabtagene vicleucel therapy. Monitor immunoglobulin levels after idecabtagene vicleucel therapy and administer immunoglobulin (IVIG) replacement for IgG less than 400 mg/dL; also, manage immunoglobulin deficiency with infection precautions and prophylactic antibiotic or antiviral therapy per standard guidelines.
Viral reactivation including cytomegalovirus (CMV) infection and hepatitis B exacerbation/hepatitis B virus (HBV) infection may occur with idecabtagene vicleucel therapy. CMV infection resulting in pneumonia and death was reported. Monitor for CMV reactivation after idecabtagene vicleucel therapy; treat CMV infection per clinical guidelines. HBV reactivation resulting in hepatitis B exacerbation, fulminant hepatitis, hepatic failure, and death may occur with drugs directed against plasma cells, such as idecabtagene vicleucel. Screen all patients for CMV, HBV, hepatitis C virus, and HIV prior to cell collection (leukapheresis). Consider antiviral therapy to prevent viral reactivation.
Patients who receive idecabtagene vicleucel should avoid cell, organ, tissue, and blood donation.
False-positive HIV test results have been reported in patients who received treatment with chimeric antigen receptor (CAR) T-cell immunotherapy, such as idecabtagene vicleucel. The use of gammaretroviral or lentiviral vectors to reprogram T-cells as part of CAR T-cell therapy has resulted in laboratory test interference with HIV-1 nucleic acid amplification testing (NAAT). False test results may occur due to vector interference with long terminal repeat (LTR) genomes in HIV NAAT. Alternative testing methods for HIV (e.g., assays that target p24 antigen and anti-HIV-1 antibodies or the integrase gene) should be performed in patients who have received CAR T-cell therapy.
Use of idecabtagene vicleucel is not recommended in pregnant women; pregnancy after idecabtagene vicleucel administration should be discussed with the treating physician. There are no available data with idecabtagene vicleucel use in pregnant women; animal reproductive and developmental toxicity studies have not been conducted. It is not known if idecabtagene vicleucel has the potential to be transferred to the fetus. However, based on its mechanism of action, fetal toxicity including plasma cell aplasia or hypogammaglobulinemia may occur if the transduced cells cross the placenta.
Counsel patients about the reproductive risk and contraception requirements during idecabtagene vicleucel treatment. Sexually active females of reproductive potential should undergo pregnancy testing prior to idecabtagene vicleucel therapy. See prescribing information for fludarabine and cyclophosphamide for information on the need for effective contraception in patients who receive lymphodepleting chemotherapy. There are insufficient data to recommend a duration of contraception following treatment with idecabtagene vicleucel. There are no data on the effect of idecabtagene vicleucel on fertility.
It is not known if idecabtagene vicleucel is secreted in human milk or if it has effects on the breast-fed infant or on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for idecabtagene vicleucel and any potential adverse effects on the breast-fed infant from idecabtagene vicleucel or from the underlying maternal condition.
For the treatment of multiple myeloma:
-for the treatment of relapsed or refractory multiple myeloma in patients who have received 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody:
Intravenous dosage:
Adults: 300 to 460 X 106 CAR-positive T-cells infused as a single-dose which may be suspended in 1 or more patient-specific infusion bag(s). Premedicate patients with acetaminophen 650 mg PO and diphenhydramine 12.5 mg IV or 25 to 50 mg PO (or another H1-antihistamine) approximately 30 to 60 minutes prior to the idecabtagene vicleucel infusion. Additionally, confirm that 2 doses of tocilizumab are available for each patient prior to the infusion. The overall response rate (assessed by an independent review committee) was 73% (complete response rate, 33%) in evaluable patients with relapsed or refractory multiple myeloma who received a single dose of idecabtagene vicleucel in a phase 2 trial (the KarMMa trial; n = 128). At a median follow-up time of 13.3 (range, 0.2 to 21.2) months, the median time to response was 1 (range, 0.5 to 8.8) month, the median duration of response was 10.7 months, the median progression-free survival (PFS) time was 8.8 months, and the median overall survival time was 19.4 months. Following leukapheresis and T-cell collection, all patients had lymphocyte depletion with fludarabine (30 mg/m2 IV daily for 3 doses) and cyclophosphamide (300 mg/m2 IV daily for 3 doses) starting 5 days prior to the target infusion date of idecabtagene vicleucel. Bridging chemotherapy between leukapheresis and lymphodepleting chemotherapy was given in 88% of patients. In this trial, patients (median age, 61 years; range 33 to 78 years) had received a median of 6 (range, 3 to 16) prior therapies that must have included an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody; 94% of patients had previously received an autologous stem-cell transplant (SCT). The median PFS time (assessed by an independent response committee) was significantly improved in patients with relapsed or refractory multiple myeloma who received a single dose of idecabtagene vicleucel compared with standard multiple myeloma therapy (13.3 months vs. 4.4 months; hazard ratio = 0.49; 95% CI, 0.38 to 0.65, p less than 0.001) in a randomized (2:1) phase 3 (KarMMa-3) trial (n = 386). Bridging chemotherapy between leukapheresis and lymphodepleting chemotherapy was given in 84% of patients who received idecabtagene vicleucel. In this trial, patients (median age, 63 years; range 30 to 83 years) had received a median of 3 (range 2 to 4) prior therapies that included daratumumab, an immunomodulatory agent, and a proteasome inhibitor for at least 2 consecutive cycles and had documented disease progression within 60 days of their last dose of therapy; 84% of patients in the idecabtagene vicleucel arm had previously received an autologous SCT.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Cytokine Release Syndrome (CRS)
NOTE: Do not exceed 3 tocilizumab doses in a 24-hour period. Do not exceed 4 doses if there is no clinical improvement in CRS. If corticosteroids are initiated for CRS, continue for at least 3 doses; taper over a maximum of 7 days.
Grade 1 toxicity (i.e., fever, nausea, fatigue, headache, myalgia, malaise): For onset at 72 hours or more after the infusion, treat symptomatically. For onset at less than 72 hours, consider giving tocilizumab 8 mg/kg IV over 1 hour (maximum dose, 800 mg) and dexamethasone 10 mg IV every 24 hours.
Grade 2 toxicity (i.e., oxygen requirement less than 40% FiO2, hypotension responsive to fluids or a low-dose of 1 vasopressor agent, or grade 2 organ toxicity): Administer tocilizumab 8 mg/kg IV over 1 hour (maximum dose, 800 mg); repeat tocilizumab 8 mg/kg IV every 8 hours as needed if the patient is not responding to IV fluids or increasing supplemental oxygen. Consider starting dexamethasone 10 mg IV every 12 to 24 hours. If there is no improvement within 24 hours or rapid progression, repeat tocilizumab and increase the dexamethasone dosage to 20 mg IV every 6 to 12 hours. If there is no improvement within 24 hours or continued rapid progression, discontinue dexamethasone and start methylprednisolone (2 mg/kg IV once, then 0.5 mg/kg IV every 6 hours). Consider an alternative anti-cytokine agent after 2 doses of tocilizumab.
Grade 3 toxicity (i.e., fever, oxygen requirement of 40% FiO2 or more, hypotension requiring high-dose or multiple vasopressor agents, grade 3 organ toxicity, or grade 4 transaminitis): Administer tocilizumab 8 mg/kg IV over 1 hour (maximum dose, 800 mg); repeat tocilizumab 8 mg/kg IV every 8 hours as needed if the patient is not responding to IV fluids or increasing supplemental oxygen. Start dexamethasone 10 mg IV every 12 hours. If there is no improvement within 24 hours or rapid progression, repeat tocilizumab and increase the dexamethasone dosage to 20 mg IV every 6 to 12 hours. If there is no improvement within 24 hours or continued rapid progression, discontinue dexamethasone and start methylprednisolone (2 mg/kg IV once, then 0.5 mg/kg IV every 6 hours). Consider an alternative anti-cytokine agent after 2 doses of tocilizumab.
Grade 4 toxicity (i.e., requirements for ventilator support, continuous veno-venous hemodialysis (CVVHD), or grade 4 organ toxicity (excluding transaminitis): Consider intensive care supportive therapy. Administer tocilizumab 8 mg/kg IV over 1 hour (maximum dose, 800 mg); repeat tocilizumab 8 mg/kg IV every 8 hours as needed if the patient is not responding to IV fluids or increasing supplemental oxygen. Start dexamethasone 20 mg IV every 6 hours. Consider an alternative anti-cytokine agent after 2 doses of tocilizumab. If there is no improvement within 24 hours, consider methylprednisolone (1 to 2 grams repeated every 24 hours if needed; taper as clinically indicated) or other anti-T-cell therapies.
Neurologic Toxicity
NOTE: Start seizure prophylaxis with a non-sedating anti-seizure medication (e.g., levetiracetam) for any grade neurotoxicity.
Grade 1 toxicity: For onset at 72 hours or more after the infusion, observation only. For onset at less than 72 hours, consider giving dexamethasone 10 mg IV every 12 to 24 hours for 2 to 3 days.
Grade 2 toxicity (excluding isolated grade 2 headaches): Start dexamethasone 10 mg IV every 12 hours for 2 to 3 days (or longer if symptoms persist); consider tapering for a total corticosteroid exposure of greater than 3 days. If there is no improvement after 24 hours or worsening toxicity, increase the dosage of dexamethasone up to a maximum of 20 mg IV every 6 hours.
Grade 3 toxicity (excluding isolated grade 3 headaches): Start dexamethasone 10 to 20 mg IV every 6 to 12 hours. If there is no improvement after 24 hours or worsening toxicity, escalate to methylprednisolone (2 mg/kg IV once, then 0.5 mg/kg IV every 6 hours; taper within 7 days). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy and start high-dose methylprednisolone (1 to 2 grams repeated every 24 hours if needed; taper as clinically indicated) and cyclophosphamide 1.5 grams/m2.
Grade 4 toxicity: Start dexamethasone 20 mg IV every 6 hours. If there is no improvement after 24 hours or worsening toxicity, escalate to high-dose methylprednisolone (i.e., 1 to 2 grams repeated every 24 hours if needed; taper as clinically indicated). If cerebral edema is suspected, consider hyperventilation and hyperosmolar therapy and start high-dose methylprednisolone (i.e., 1 to 2 grams repeated every 24 hours if needed; taper as clinically indicated) and cyclophosphamide 1.5 grams/m2.
Concurrent CRS and Neurologic Toxicity
If concurrent CRS is suspected during the neurologic toxicity event OR if concurrent neurologic toxicity is suspected during CRS, administer:
-corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades.
-tocilizumab according to CRS grade.
-antiseizure medication according to neurologic toxicity.
Maximum Dosage Limits:
-Adults
460 x 106 CAR-positive T-cells as a single IV dose.
-Geriatric
460 x 106 CAR-positive T-cells as a single IV dose.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Bacillus Calmette-Guerin Vaccine, BCG: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Chikungunya Vaccine, Live: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Intranasal Influenza Vaccine: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Live Vaccines: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Measles/Mumps/Rubella Vaccines, MMR: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Rotavirus Vaccine: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Smallpox Vaccine, Vaccinia Vaccine: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Typhoid Vaccine: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Varicella-Zoster Virus Vaccine, Live: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Yellow Fever Vaccine, Live: (Contraindicated) Avoid administration of live virus vaccines in the six weeks prior to the start of lymphodepleting chemotherapy, during idecabtagene vicleucel therapy, and prior to immune recovery following treatment with idecabtagene vicleucell. Patients with altered immunocompetence, including those receiving or those that have recently received immunosuppressive drug therapy, may be at increased risk for an adverse reaction because of uninhibited growth of the attenuated live virus. Additionally, vaccines may be less effective if administered during a period of altered immunocompetence.
Idecabtagene vicleucel is a chimeric antigen receptor (CAR) T-cell therapy that works by redirecting T-cells to target the B-cell maturation antigen (BCMA) antigen on plasma cells. The domains, CD137 (4-1BB) and CD3-zeta, activate downstream signaling cascades that lead to T-cell activation, proliferation, secretion of chemokines, and lysis of BCMA-expressing cells.
This immunotherapy involves removing, genetically modifying, and then re-infusing a patient's own T-cells. During the manufacturing process, the cells are genetically modified using lentiviral vector transduction to express a CAR comprised of a murine anti- BCMA- single chain variable fragment linked to CD137 (4-1BB) and CD3-zeta co-stimulatory domains.
To produce CAR T-cell therapy, T-cells are collected from the blood by leukapheresis; enriched; activated with anti-CD3 and anti-CD28 antibodies in the presence of IL-2; transduced with the replication incompetent retroviral vector containing the anti-BCMA CAR transgene; expanded to large numbers in a cell culture; and then washed, formulated into a suspension, and cryopreserved.
Idecabtagene vicleucel is administered intravenously. Post infusion, it exhibits CAR-positive cell proliferation and rapid expansion followed by a bi-exponential decline.
Pharmacodynamics: Peak levels of plasma cytokines, chemokines, and soluble immune mediators were observed within 14 days of the idecabtagene vicleucel infusion; these levels typically returned to baseline within 1 month.
-Route-Specific Pharmacokinetics
Intravenous Route
The geometric mean Cmax level was 256,333 copies/mcg (coefficient of variation (CV), 165%) and the geometric mean AUC(0-28 days) value was 3,088,455 day x copies/mcg (CV, 190%) in patients with relapsed or refractory multiple myeloma who received idecabtagene vicleucel (n = 99) in a clinical trial. The idecabtagene vicleucel median Cmax level was 4.6-fold higher in 72 patients who achieved a response compared with 27 patients who were nonresponders in this trial. Additionally, the median idecabtagene vicleucel AUC(0-28 days) value was 5.6-fold higher in responders. The median time to maximal expansion in peripheral blood of idecabtagene vicleucel (Tmax) occurred 11 days (range, 7 to 28 days) following the idecabtagene vicleucel infusion; it was present in peripheral blood for up to 1 year.
-Special Populations
Geriatric
Age (range, 33 to 78 years) had no significant impact on idecabtagene vicleucel expansion parameters.
Gender Differences
Gender had no significant impact on idecabtagene vicleucel expansion parameters.
Ethnic Differences
Race or ethnicity had no significant impact on idecabtagene vicleucel expansion parameters.
Obesity
Patients with lower body weights had higher idecabtagene vicleucel cell expansion; however, the effect of weight on cell expansion was not considered clinically relevant.
Other
Immunosuppressive therapy
The idecabtagene vicleucel Cmax and AUC(0-28 days) values were 1.3-fold and 1.6-fold higher, respectively, in patients who received tocilizumab to treat cytokine release syndrome compared with patients who did not receive tocilizumab. Additionally, the idecabtagene vicleucel Cmax and AUC(0-28 days) values were 1.7-fold and 2.2-fold higher, respectively, in patients who received corticosteroids compared with patients who did not receive corticosteroids.