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Carvykti is a brand name for Ciltacabtagene Autoleucel. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: CARVYKTI is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. 3
Verbatim from this product's EMA label. Tap a section to expand.
CARVYKTI must be administered in a qualified treatment centre. Therapy should be initiated under the direction and supervision of a healthcare professional experienced in the treatment of haematological malignancies and trained for administration and management of patients treated with CARVYKTI.
4). In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, suitable alternative measures to treat CRS instead of tocilizumab must be available prior to infusion.
Emergency equipment must be available prior to infusion and during the recovery period. 4). Treatment consists of a single dose for infusion containing a dispersion of CAR-positive viable T cells in one infusion bag. 75 x 106 CAR-positive viable T cells/kg of body weight (not exceeding 1 × 108 CAR-positive viable T cells).
5 - 1 x 106 CAR-positive viable T cells/kg body weight. 5 - 1 x 108 CAR-positive viable T cells (non-weight based). See the accompanying Lot information sheet (LIS) for additional information pertaining to dose. 4). 1). The availability of CARVYKTI should be confirmed prior to starting the lymphodepleting regimen.
A lymphodepleting regimen of cyclophosphamide 300 mg/m2 intravenous and fludarabine 30 mg/m2 intravenous should be administered daily for 3 days. CARVYKTI infusion should be administered 5 to 7 days after the start of the lymphodepleting regimen.
If resolution of toxicities due to the lymphodepleting regimen to Grade 1 or lower takes more than 14 days, thereby resulting in delays to CARVYKTI dosing, the lymphodepleting regimen should be re-administered after a minimum of 21 days following the first dose of the first lymphodepleting regimen.
For dose modifications of cyclophosphamide and fludarabine, see corresponding Summaries of Product Characteristics of cyclophosphamide and fludarabine. Premedication The following pre-infusion medications should be administered to all patients 30 to 60 minutes prior to CARVYKTI infusion: Antipyretic (oral or intravenous paracetamol 650 to 1,000 mg).
Antihistamine (oral or intravenous diphenhydramine 25 to 50 mg or equivalent). The use of prophylactic systemic corticosteroids should be avoided as it may interfere with the activity of CARVYKTI. Special populations Elderly No dose adjustment is required in patients ≥ 65 years of age.
Summary of the safety profile The safety of CARVYKTI was evaluated in 396 adult patients with multiple myeloma infused with CARVYKTI in three open label clinical trials: Study MMY2001 (N=106), which included patients from the main Phase 1b/2 cohort (United States; n=97) and an additional cohort (Japan; n=9), Phase 2 Study MMY2003 (N=94) and Phase 3 Study MMY3002 (N=196).
Patients who complete Study MMY2001, MMY2003, or MMY3002 are eligible to enroll in a separate long-term follow-up study (MMY4002). The most common CARVYKTI adverse reactions (≥20%) were neutropenia (90%), pyrexia (85%), CRS (83%), thrombocytopenia (60%), anemia (60%), musculoskeletal pain (40%), lymphopenia (38%), fatigue (35%), leukopenia (34%), hypotension (34%), hypogammaglobulinaemia (33%), diarrhea (32%), upper respiratory tract infection (32%), transaminase elevation (26%), headache (25%), nausea (23%), and cough (22%).
Serious adverse reactions occurred in 44% of patients; serious adverse reactions reported in ≥2% of patients were CRS (11%), pneumonia (9%), sepsis (5%), viral infection (5%), neutropenia (4%), cranial nerve palsies, (4%), ICANS (4%), encephalopathy (3%), upper respiratory tract infection (3%), bacterial infections (2%), gastroenteritis (2%), febrile neutropenia (2%), thrombocytopenia (2%), haemophagocytic lymphohistiocytosis (2%), motor dysfunction (2%), dyspnea (2%), diarrhea (2%), and renal failure (2%).
15 The most common (≥5%) Grade ≥ 3 non-haematological adverse reactions were transaminase elevation (11%), pneumonia (11%), febrile neutropenia (8%), sepsis (7%), pyrexia (7%), Gamma- glutamyltransferase increased (6%), hypotension (6%), bacterial infection (5%), and hypogammaglobulinaemia (5%).
The most common (≥20%) Grade ≥3 haematological abnormalities were neutropenia (89%), thrombocytopenia (45%), anaemia (44%), lymphopenia (36%), and leukopenia (33%). Tabulated list of adverse reactions Table 4 summarises the adverse reactions that occurred in patients receiving CARVYKTI.
Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability, the name of the medicinal product, the batch number and the name of the treated patient should be kept for a period of 30 years after the expiry date of the medicinal product.
General Autologous use CARVYKTI is intended solely for autologous use and must not, under any circumstances, be administered to other patients. CARVYKTI must not be infused if the information on the product labels and Lot Information Sheet does not match the patient’s identity.
Clinical assessment prior to CARVYKTI infusion CARVYKTI infusion should be delayed if a patient has any of the following conditions: clinically significant active infection or inflammatory disorders, 5 grade ≥ 3 non-haematologic toxicities of cyclophosphamide and fludarabine lymphodepletion regimen, except for Grade 3 nausea, vomiting, diarrhoea, or constipation.
CARVYKTI infusion should be delayed until resolution of these events to Grade ≤ 1, active graft versus host disease. Patients with active or prior history of significant central nervous system (CNS) disease or inadequate renal, hepatic, pulmonary, or cardiac function are likely to be more vulnerable to the consequences of the adverse reactions described below and require special attention.
There is no experience of use of CARVYKTI in patients with CNS involvement of myeloma or other pre-existing, clinically relevant CNS illnesses. The efficacy/safety of CARVYKTI in patients previously exposed to other anti-BCMA treatments is unknown.
There is limited evidence available on efficacy/safety of CARVYKTI in re-treated patients. Rapidly progressing disease When considering patients for CARVYKTI treatment, physicians should assess the impact of rapidly progressing disease on the ability of patients to receive CAR-T infusion.
1. Contraindications of the lymphodepleting chemotherapy and supportive therapy should be considered.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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4 Patients seropositive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) There is currently no experience with manufacturing CARVYKTI for patients testing positive for HIV, active HBV, or active HCV.
Screening for HBV, HCV and HIV and other infectious agents must be performed before collection of cells for manufacturing. Paediatric population The safety and efficacy of CARVYKTI in children aged below 18 years of age have not been established.
No data are available. Method of administration CARVYKTI is for intravenous use only. Do NOT use a leukodepleting filter. Preparation of CARVYKTI for infusion Prior to infusion and during the recovery period, the availability of tocilizumab, or suitable alternatives, in the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, and emergency equipment must be ensured.
Before infusion, it must be confirmed that the patient’s identity matches the unique patient information on the CARVYKTI cryo cassette, infusion bag and on the Lot Information Sheet. 4). The medicinal product must not be thawed until it is ready to be used.
The timing of CARVYKTI thaw and infusion should be coordinated; the infusion time should be confirmed in advance, and the start time for thaw must be adjusted so that CARVYKTI is available for infusion when the patient is ready. 5 hours of thawing.
6.
Within each system organ class, the adverse reactions are ranked by frequency. Within each frequency grouping, where relevant, adverse reactions are presented in order of decreasing seriousness using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).
1 # Contains fatal outcome(s). * Based on grouped term. 1 Sepsis includes bacteraemia, bacterial sepsis, candida sepsis, device related bacteraemia, enterococcal bacteraemia, enterococcal sepsis, haemophilus sepsis, neutropenic sepsis, pseudomonal bacteraemia, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteraemia, streptococcal sepsis, systemic candida, and urosepsis.
2 Gastroenteritis includes enterocolitis bacterial, enterocolitis infectious, enterocolitis viral, enterovirus infection, gastroenteritis, gastroenteritis cryptosporidial, gastroenteritis rotavirus, gastroenteritis salmonella, gastroenteritis viral, gastroenteritis escherichia coli, gastrointestinal infection, and large intestine infection.
3 Urinary tract infection includes cystitis, escherichia urinary tract infection, urinary tract infection, urinary tract […]
Some patients may not benefit from CARVYKTI treatment due to potential increased risk of early death if disease progresses rapidly during bridging therapy. 4). Patients should be instructed to remain within proximity of a qualified clinical facility for at least 4 weeks following infusion.
Cytokine release syndrome Cytokine release syndrome, including fatal or life-threatening reactions, can occur after CARVYKTI infusion. 8). The median time from CARVYKTI infusion (Day 1) to onset of CRS was 7 days (range: 1 to 23 days).
Approximately 83% of patients experienced CRS onset after Day 3 of receiving the CARVYKTI infusion. In almost all cases, duration of CRS ranged from 1 to 18 days (median duration, 4 days). Eighty-nine percent of patients had a CRS duration of ≤ 7 days.
Clinical signs and symptoms of CRS may include, but are not limited to, fever (with or without rigors), chills, hypotension, hypoxia and elevated liver enzymes. Potentially life-threatening complications of CRS may include cardiac dysfunction, neurologic toxicity and haemophagocytic lymphohistiocytosis (HLH).
Patients who develop HLH may have an increased risk of severe bleeding. Patients should be closely monitored for signs or symptoms of these events, including fever. Risk factors for severe CRS include high pre-infusion tumour burden, active infection and early onset of fever or persistent fever after 24 hours of symptomatic treatment.
2). Appropriate prophylactic and therapeutic treatment for infections should be provided, and complete resolution of any active infections should be ensured prior to CARVYKTI infusion. Infections may also occur concurrently with CRS and may increase the risk of a fatal event.
The availability of at least one dose of tocilizumab for use in the event of CRS should be ensured prior to infusion. The qualified treatment centre must have access to an additional dose of tocilizumab within 8 hours of each previous dose.
In the exceptional case where tocilizumab is not available due to 6 a shortage that is listed in the European Medicines Agency shortage catalogue, the treatment centre must have access to suitable alternative measures instead of tocilizumab to treat CRS.
Patients should be monitored for signs and symptoms of CRS daily for 14 days after the CARVYKTI infusion at a qualified clinical facility, and then periodically for an additional two weeks after CARVYKTI infusion. Patients should be counselled to seek immediate medical attention should signs or symptoms of CRS occur at any time.
At the first sign of CRS, the patient should be immediately evaluated for hospitalisation and treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids should be instituted as indicated in Table 1 below. Evaluation for HLH should be considered in patients with severe or unresponsive CRS.
For patients with high pre-infusion tumour burden, early onset of fever, or persistent fever after 24 hours, early tocilizumab should be considered. The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), should be avoided during CRS.
2). Management of cytokine release syndrome associated with CARVYKTI If CRS is suspected, manage according to the […]