Source: European Medicines Agency (EU) Revision Year: 2022 Publisher: 7. MARKETING AUTHORISATION HOLDER, Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Cytokine release syndrome, including life-threatening or fatal reactions, may occur in patients receiving TECVAYLI.
Clinical signs and symptoms of CRS may include but are not limited to fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes. Potentially life-threatening complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
Treatment should be initiated with TECVAYLI according to the step-up dosing schedule to reduce risk of CRS. Pre-treatment medicinal products (corticosteroids, antihistamine and antipyretics) should be administered prior to each dose of the TECVAYLI step-up dosing schedule to reduce risk of CRS (see section 4.2).
The following patients should be instructed to remain within proximity of a healthcare facility and monitored daily for 48 hours:
Patients who experience CRS following their previous dose should be administered pre-treatment medicinal products prior to the next dose of TECVAYLI.
Patients should be counselled to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, patients should be immediately evaluated for hospitalisation. Treatment with supportive care, tocilizumab and/or corticosteroids should be instituted, based on severity as indicated in Table 4 below. The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), has the potential to worsen CRS symptoms and should be avoided during CRS. Treatment with TECVAYLI should be withheld until CRS resolves as indicated in Table 3 (see section 4.2).
CRS should be identified based on clinical presentation. Patients should be evaluated and treated for other causes of fever, hypoxia, and hypotension.
If CRS is suspected, TECVAYLI should be withheld until the adverse reaction resolves (see Table 3). CRS should be managed according to the recommendations in Table 4. Supportive care for CRS (including but not limited to anti-pyretic agents, intravenous fluid support, vasopressors, supplemental oxygen, etc.) should be administered as appropriate. Laboratory testing to monitor for disseminated intravascular coagulation (DIC), haematology parameters, as well as pulmonary, cardiac, renal, and hepatic function should be considered.
Table 4. Recommendations for management of cytokine release syndrome with tocilizumab and corticosteroids:
| Gradee | Presenting symptoms | Tocilizumaba | Corticosteroidsb |
|---|---|---|---|
| Grade 1 | Temperature ≥38°Cc | May be considered | Not applicable |
| Grade 2 | Temperature ≥38°Cc with either: • Hypotension responsive to fluids and not requiring vasopressors, or • Oxygen requirement of low-flow nasal cannulad or blow-by | Administer tocilizumabb 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). Repeat tocilizumab every 8 hours as needed, if not responsive to intravenous fluids or increasing supplemental oxygen. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. | If no improvement within 24 hours of starting tocilizumab, administer methylprednisolone 1 mg/kg intravenously twice daily, or dexamethasone 10 mg intravenously every 6 hours. Continue corticosteroid use until the event is Grade 1 or less, then taper over 3 days. |
| Grade 3 | Temperature ≥38°Cc with either: • Hypotension requiring one vasopressor with or without vasopressin, or • Oxygen requirement of high-flow nasal cannulad, facemask, non-rebreather mask, or Venturi mask | Administer tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). Repeat tocilizumab every 8 hours as needed, if not responsive to intravenous fluids or increasing supplemental oxygen. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. | If no improvement, administer methylprednisolone 1 mg/kg intravenously twice daily, or dexamethasone 10 mg intravenously every 6 hours. Continue corticosteroid use until the event is Grade 1 or less, then taper over 3 days. |
| Grade 4 | Temperature ≥38°Cc with either: • Hypotension requiring multiple vasopressors (excluding vasopressin), or • Oxygen requirement of positive pressure (e.g., continuous positive airway pressure [CPAP], bilevel positive airway pressure [BiPAP], intubation, and mechanical ventilation) | Administer tocilizumab 8 mg/kg intravenously over 1 hour (not to exceed 800 mg). Repeat tocilizumab every 8 hours as needed if not responsive to intravenous fluids or increasing supplemental oxygen. Limit to a maximum of 3 doses in a 24-hour period; maximum total of 4 doses. | As above, or administer methylprednisolone 1 000 mg intravenously per day for 3 days, per physician discretion. If no improvement or if condition worsens, consider alternate immunosuppressantsb. |
a Refer to tocilizumab prescribing information for details.
b Treat unresponsive CRS per institutional guidelines.
c Attributed to CRS. Fever may not always be present concurrently with hypotension or hypoxia as it may be masked by interventions such as antipyretics or anticytokine therapy (e.g., tocilizumab or corticosteroids).
d Low-flow nasal cannula is ≤6 L/min, and high-flow nasal cannula is >6 L/min.
e Based on ASTCT grading for CRS (Lee et al 2019).
Serious or life-threatening neurologic toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) may occur following treatment with TECVAYLI.
Patients should be monitored for signs or symptoms of neurologic toxicities during treatment and treated promptly.
Patients should be counselled to seek medical attention should signs or symptoms of neurologic toxicity occur. At the first sign of neurologic toxicity, including ICANS, patients should be immediately evaluated and treated based on severity. Patients who experience Grade 2 or higher ICANS or first occurrence of Grade 3 ICANS with the previous dose of TECVAYLI should be instructed to remain within proximity of a healthcare facility and monitored for signs and symptoms daily for 48 hours.
For ICANS and other neurologic toxicities, treatment with TECVAYLI should be withheld as indicated in Table 3 (see section 4.2).
Due to the potential for ICANS, patients should be advised not to drive or operate heavy machinery during the TECVAYLI step-up dosing schedule and for 48 hours after completing the TECVAYLI step-up dosing schedule and in the event of new onset of any neurological symptoms (see section 4.7).
At the first sign of neurologic toxicity, including ICANS, neurology evaluation should be considered. Other causes of neurologic symptoms should be ruled out. TECVAYLI should be withheld until adverse reaction resolves (see Table 3). Intensive care and supportive therapy should be provided for severe or life-threatening neurologic toxicities. General management for neurologic toxicity (e.g., ICANS with or without concurrent CRS) is summarised in Table 5.
Table 5. Guidelines for management of immune effector cells-associated neurotoxicity syndrome (ICANS):
| Grade | Presenting symptomsa | Concurrent CRS | No Concurrent CRS |
|---|---|---|---|
| Grade 1 | ICE score 7-9b Or, depressed level of consciousnessc: awakens spontaneously. | Management of CRS per Table 4. Monitor neurologic symptoms and consider neurology consultation and evaluation, per physician discretion. | Monitor neurologic symptoms and consider neurology consultation and evaluation, per physician discretion. |
| Consider non-sedating, anti-seizure medicinal products (e.g., levetiracetam) for seizure prophylaxis. | |||
| Grade 2 | ICE score 3-6b Or, depressed level of consciousnessc: awakens to voice. | Administer tocilizumab per Table 4 for management of CRS. If no improvement after starting tocilizumab, administer dexamethasoned 10 mg intravenously every 6 hours if not already taking other corticosteroids. Continue dexamethasone use until resolution to Grade 1 or less, then taper. | Administer dexamethasoned 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. |
| Consider non-sedating, anti-seizure medicinal products (e.g., levetiracetam) for seizure prophylaxis. Consider neurology consultation and other specialists for further evaluation, as needed. | |||
| Grade 3 | ICE score 0-2b Or, depressed level of consciousnessc : awakens only to tactile stimulus, or seizuresc, either: • any clinical seizure, focal or generalised that resolves rapidly, or • non-convulsive seizures on electroencephalogram (EEG) that resolve with intervention, or raised intracranial pressure: focal/local oedema on neuroimagingc. | Administer tocilizumab per Table 4 for management of CRS. In addition, administer dexamethasoned 10 mg intravenously with the first dose of tocilizumab, and repeat dose every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. | Administer dexamethasoned 10 mg intravenously every 6 hours. Continue dexamethasone use until resolution to Grade 1 or less, then taper. |
| Consider non-sedating, anti-seizure medicinal products (e.g., levetiracetam) for seizure prophylaxis. Consider neurology consultation and other specialists for further evaluation, as needed. | |||
| Grade 4 | ICE score 0b Or, depressed level of consciousnessc either: patient is unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma, or seizuresc, either: life-threatening prolonged seizure (>5 minutes), or repetitive clinical or electrical seizures without return to baseline in between, or motor findingsc: deep focal motor weakness such as hemiparesis or paraparesis, or raised intracranial pressure/cerebral oedemac, with signs/symptoms such as: diffuse cerebral oedema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilloedema, or cushing’s triad | Administer tocilizumab per Table 4 for management of CRS. As above, or consider administration of methylprednisolone 1 000 mg per day intravenously with first dose of tocilizumab, and continue methylprednisolone 1 000 mg per day intravenously for 2 or more days. | As above, or consider administration of methylprednisolone 1 000 mg per day intravenously for 3 days; if improves, then manage as above. |
| Consider non-sedating, anti-seizure medicinal products (e.g., levetiracetam) for seizure prophylaxis. Consider neurology consultation and other specialists for further evaluation, as needed. In case of raised intracranial pressure/cerebral oedema, refer to institutional guidelines for management. | |||
a Management is determined by the most severe event, not attributable to any other cause.
b If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (name 3 objects, e.g., point to clock, pen, button = 3 points); Following Commands (e.g., “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point); Writing (ability to write a standard sentence = 1 point; and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (Grade 4 ICANS) = 0 points.
c Attributable to no other cause.
d All references to dexamethasone administration are dexamethasone or equivalent.
Severe, life-threatening, or fatal infections have been reported in patients receiving TECVAYLI (see section 4.8). New or reactivated viral infections occurred during therapy with TECVAYLI. Progressive multifocal leukoencephalopathy (PML) has also occurred during therapy with TECVAYLI.
Patients should be monitored for signs and symptoms of infection prior to and during treatment with TECVAYLI and treated appropriately. Prophylactic antimicrobials should be administered according to local institutional guidelines.
TECVAYLI step-up dosing schedule should not be administered in patients with active infection. For subsequent doses, TECVAYLI should be withheld as indicated in Table 3 (see section 4.2).
Hepatitis B virus reactivation can occur in patients treated with medicinal products directed against B cells, and in some cases, may result in fulminant hepatitis, hepatic failure, and death.
Patients with evidence of positive HBV serology should be monitored for clinical and laboratory signs of HBV reactivation while receiving TECVAYLI, and for at least six months following the end of TECVAYLI treatment.
In patients who develop reactivation of HBV while on TECVAYLI, treatment with TECVAYLI should be withheld as indicated in Table 3 and manage per local institutional guidelines (see section 4.2).
Hypogammaglobulinaemia has been reported in patients receiving TECVAYLI (see section 4.8).
Immunoglobulin levels should be monitored during treatment with TECVAYLI. Intravenous or subcutaneous immunoglobulin therapy was used to treat hypogammaglobulinemia in 39% of patients. Patients should be treated according to local institutional guidelines, including infection precautions, antibiotic or antiviral prophylaxis, and administration of immunoglobulin replacement.
Immune response to vaccines may be reduced when taking TECVAYLI.
The safety of immunisation with live viral vaccines during or following TECVAYLI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment and least 4 weeks after treatment.
Neutropenia and febrile neutropenia have been reported in patients who received TECVAYLI (see section 4.8).
Complete blood cell counts should be monitored at baseline and periodically during treatment. Supportive care should be provided per local institutional guidelines.
Patients with neutropenia should be monitored for signs of infection.
Treatment with TECVAYLI should be withheld as indicated in Table 3 (see section 4.2).
This medicinal product contains less than 1 mmol (23 mg) sodium per dose, that is to say essentially ‘sodium-free’.
No interaction studies have been performed with TECVAYLI.
The initial release of cytokines associated with the start of TECVAYLI treatment could suppress CYP450 enzymes. The highest risk of interaction is expected to be from initiation of TECVAYLI step-up schedule up to 7 days after the first maintenance dose or during a CRS event. During this time period, toxicity or medicinal product concentrations (e.g., cyclosporine) should be monitored in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index. The dose of the concomitant medicinal product should be adjusted as needed.
Pregnancy status for females of child-bearing potential should be verified prior to starting treatment with TECVAYLI.
Women of child-bearing potential should use effective contraception during treatment and for 3 months after the final dose of TECVAYLI. In clinical studies, male patients with a female partner of child-bearing potential used effective contraception during treatment and for three months after the last dose of teclistamab.
There are no available data on the use of teclistamab in pregnant women or animal data to assess the risk of teclistamab in pregnancy. Human IgG is known to cross the placenta after the first trimester of pregnancy. Therefore, teclistamab, a humanised IgG4-based antibody, has the potential to be transmitted from the mother to the developing foetus. TECVAYLI is not recommended for women who are pregnant. TECVAYLI is associated with hypogammaglobulinaemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered.
It is not known whether teclistamab is excreted in human or animal milk, affects breast-fed infants or affects milk production. Because of the potential for serious adverse reactions in breast-fed infants from TECVAYLI, patients should be advised not to breast-feed during treatment with TECVAYLI and for at least three months after the last dose.
There are no data on the effect of teclistamab on fertility. Effects of teclistamab on male and female fertility have not been evaluated in animal studies.
TECVAYLI has major influence on the ability to drive and use machines.
Due to the potential for ICANS, patients receiving TECVAYLI are at risk of depressed level of consciousness (see section 4.8). Patients should be instructed to avoid driving and operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurological symptoms (Table 1) (see section 4.2 and section 4.4).
The most frequent adverse reactions of any grade in patients were hypogammaglobulinaemia (75%), cytokine release syndrome (72%), neutropenia (71%), anaemia (55%), musculoskeletal pain (52%), fatigue (41%), thrombocytopenia (40%), injection site reaction (38%), upper respiratory tract infection (37%), lymphopenia (35%), diarrhoea (28%), pneumonia (28%), nausea (27%), pyrexia (27%), headache (24%), cough (24%), constipation (21%) and pain (21%).
Serious adverse reactions were reported in 65% patients who received TECVAYLI, including pneumonia (16%), COVID-19 (15%), cytokine release syndrome (8%), sepsis (7%), pyrexia (5%), musculoskeletal pain (5%), acute kidney injury (4.8%), diarrhoea (3.0%), cellulitis (2.4%), hypoxia (2.4%), febrile neutropenia (2.4%), and encephalopathy (2.4%).
The safety data of TECVAYLI was evaluated in MajesTEC-1, which included 165 adult patients with multiple myeloma who received the recommended dosing regimen of TECVAYLI as monotherapy. The median duration of TECVAYLI treatment was 8.5 (Range: 0.2 to 24.4) months.
Table 6 summarises adverse reactions reported in patients who received TECVAYLI. The safety data of TECVAYLI was also evaluated in the all treated population (N=302) with no additional adverse reactions identified.
Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: 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) and not known (frequency cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Table 6. Adverse reactions in patients with multiple myeloma treated with TECVAYLI in MajesTEC-1 at the recommended dose for monotherapy use:
| System Organ Class | Adverse Reaction | Frequency (All grades) | N=165 | |
|---|---|---|---|---|
| n (%) | ||||
| Any Grade | Grade 3 or 4 | |||
| Infections and infestations | Pneumonia1 | Very common | 46 (28%) | 32 (19%) |
| Sepsis2 | Common | 13 (7.9%) | 11 (6.7%) | |
| COVID-193 | Very common | 30 (18%) | 20 (12%) | |
| Upper respiratory tract infection4 | Very common | 61 (37%) | 4 (2.4%) | |
| Cellulitis | Common | 7 (4.2%) | 5 (3.0%) | |
| Blood and lymphatic system disorders | Neutropenia | Very common | 117 (71%) | 106 (64%) |
| Febrile neutropenia | Common | 6 (3.6%) | 5 (3.0%) | |
| Thrombocytopenia | Very common | 66 (40%) | 35 (21%) | |
| Lymphopenia | Very common | 57 (35%) | 54 (33%) | |
| Anaemia5 | Very common | 90 (55%) | 61 (37%) | |
| Leukopenia | Very common | 29 (18%) | 12 (7.3%) | |
| Hypofibrinogenaemia | Common | 16 (9.7%) | 2 (1.2%) | |
| Immune system disorders | Cytokine release syndrome | Very common | 119 (72%) | 1 (0.6%) |
| Hypogammaglobulinaemia6 | Very common | 123 (75%) | 3 (1.8%) | |
| Metabolism and nutrition disorders | Hyperamylasaemia | Common | 6 (3.6%) | 4 (2.4%) |
| Hyperkalaemia | Common | 8 (4.8%) | 2 (1.2%) | |
| Hypercalcaemia | Very common | 19 (12%) | 5 (3.0%) | |
| Hyponatraemia | Common | 13 (7.9%) | 8 (4.8%) | |
| Hypokalaemia | Very common | 23 (14%) | 8 (4.8%) | |
| Hypocalcaemia | Common | 12 (7.3%) | 0 | |
| Hypophosphataemia | Very common | 20 (12%) | 10 (6.1%) | |
| Hypoalbuminaemia | Common | 4 (2.4%) | 1 (0.6%) | |
| Hypomagnesaemia | Very common | 22 (13%) | 0 | |
| Decreased appetite | Very common | 20 (12%) | 1 (0.6%) | |
| Nervous system disorders | Immune effector cell- associated neurotoxicity syndrome | Common | 5 (3.0%) | 0 |
| Encephalopathy7 | Common | 16 (9.7%) | 0 | |
| Neuropathy peripheral8 | Very common | 26 (16%) | 1 (0.6%) | |
| Headache | Very common | 39 (24%) | 1 (0.6%) | |
| Vascular disorders | Hemorrhage9 | Very common | 20 (12%) | 5 (3.0%) |
| Hypertension10 | Very common | 21 (13%) | 9 (5.5%) | |
| Respiratory, thoracic and mediastinal disorders | Hypoxia | Common | 16 (9.7%) | 6 (3.6%) |
| Dyspnoea11 | Very common | 22 (13%) | 3 (1.8%) | |
| Cough12 | Very common | 39 (24%) | 0 | |
| Gastrointestinal disorders | Diarrhoea | Very common | 47 (28%) | 6 (3.6%) |
| Vomiting | Very common | 21 (13%) | 1 (0.6%) | |
| Nausea | Very common | 45 (27%) | 1 (0.6%) | |
| Constipation | Very common | 34 (21%) | 0 | |
| Musculoskeletal and connective tissue disorders | Musculoskeletal pain13 | Very common | 85 (52%) | 14 (8.5%) |
| General disorders and administration site conditions | Pyrexia | Very common | 45 (27%) | 1 (0.6%) |
| Injection site reaction14 | Very common | 62 (38%) | 1 (0.6%) | |
| Pain15 | Very common | 34 (21%) | 3 (1.8%) | |
| Oedema16 | Very common | 23 (14%) | 0 | |
| Fatigue17 | Very common | 67 (41%) | 5 (3.0%) | |
| Investigations | Blood creatinine increased | Common | 9 (5.5%) | 0 |
| Transaminase elevation18 | Common | 16 (9.7%) | 4 (2.4%) | |
| Lipase increased | Common | 10 (6.1%) | 2 (1.2%) | |
| Blood alkaline phosphatase increased | Very common | 18 (11%) | 3 (1.8%) | |
| Gamma- glutamyltransferase increased | Common | 16 (9.7%) | 5 (3.0%) | |
| Activated partial thromboplastin time prolonged | Common | 13 (7.9%) | 2 (1.2%) | |
| International normalised ratio increased | Common | 10 (6.1%) | 2 (1.2%) | |
Adverse events are coded using MedDRA Version 24.0.
Note: The output includes the diagnosis of CRS and ICANS; the symptoms of CRS or ICANS are excluded.
1 Pneumonia includes Enterobacter pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, Metapneumovirus pneumonia, Pneumocystis jirovecii pneumonia, pneumonia, Pneumonia adenoviral, Pneumonia bacterial, Pneumonia klebsiella, Pneumonia moraxella, Pneumonia pneumococcal, Pneumonia pseudomonal, Pneumonia respiratory syncytial viral, Pneumonia staphylococcal and Pneumonia viral.
2 Sepsis includes bacteraemia, Meningococcal sepsis, neutropenic sepsis, Pseudomonal bacteraemia, Pseudomonal sepsis, sepsis and Staphylococcal bacteraemia.
3 COVID-19 includes asymptomatic COVID-19 and COVID-19.
4 Upper respiratory tract infection includes bronchitis, nasopharyngitis, pharyngitis, respiratory tract infection, respiratory tract infection bacterial, rhinitis, rhinovirus infection, sinusitis, tracheitis, upper respiratory tract infection and viral upper respiratory tract infection.
5 Anaemia includes anaemia, iron deficiency and iron deficiency anaemia.
6 Hypogammaglobulinaemia includes patients with adverse events of hypogammaglobulinaemia, hypoglobulinaemia, immunoglobulins decreased, and/or patients with laboratory IgG levels below 500 mg/dL following treatment with teclistamab.
7 Encephalopathy includes confusional state, depressed level of consciousness, lethargy, memory impairment and somnolence.
8 Neuropathy peripheral includes dysaesthesia, hypoaesthesia, hypoaesthesia oral, neuralgia, paraesthesia, paraesthesia oral, peripheral sensory neuropathy and sciatica.
9 Hemorrhage includes conjunctival haemorrhage, epistaxis, haematoma, haematuria, haemoperitoneum, haemorrhoidal haemorrhage, lower gastrointestinal haemorrhage, melaena, mouth haemorrhage and subdural haematoma.
10 Hypertension includes essential hypertension and hypertension.
11 Dyspnoea includes acute respiratory failure, dyspnoea and dyspnoea exertional.
12 Cough includes allergic cough, cough, productive cough and upper-airway cough syndrome.
13 Musculoskeletal pain includes arthralgia, back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain and pain in extremity.
14 Injection site reaction includes injection site bruising, injection site cellulitis, injection site discomfort, injection site erythema, injection site haematoma, injection site induration, injection site inflammation, injection site oedema, injection site pruritus, injection site rash, injection site reaction and injection site swelling.
15 Pain includes ear pain, flank pain, groin pain, non-cardiac chest pain, oropharyngeal pain, pain, pain in jaw, toothache and tumour pain.
16 Oedema includes face oedema, fluid overload, oedema peripheral and peripheral swelling.
17 Fatigue includes asthenia, fatigue and malaise
18 Transaminase elevation includes alanine aminotransferase increased and aspartate aminotransferase increased.
In MajesTEC-1 (N=165), CRS was reported in 72% of patients following treatment with TECVAYLI. One-third (33%) of patients experienced more than one CRS event. Most patients experienced CRS following Step-up Dose 1 (44%), Step-up Dose 2 (35%), or the initial maintenance dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. CRS events were Grade 1 (50%) and Grade 2 (21%) or Grade 3 (0.6%). The median time to onset of CRS was 2 (Range: 1 to 6) days after the most recent dose, with a median duration of 2 (Range: 1 to 9) days.
The most frequent signs and symptoms associated with CRS were fever (72%), hypoxia (13%), chills (12%), hypotension (12%), sinus tachycardia (7%), headache (7%), and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation) (3.6% each).
In MajesTEC-1, tocilizumab, corticosteroids and tocilizumab in combination with corticosteroids were used to treat CRS in 32%, 11% and 3% of CRS events, respectively.
In MajesTEC-1 (N=165), neurologic toxicity events were reported in 15% of patients receiving TECVAYLI. Neurologic toxicity events were Grade 1 (8.5%), Grade 2 (5.5%), or Grade 4 (<1%). The most frequently reported neurologic toxicity event was headache (8%).
ICANS was reported in 3% of patients receiving TECVAYLI at the recommended dose. The most frequent clinical manifestation of ICANS reported were confusional state (1.2%) and dysgraphia (1.2%). The onset of neurologic toxicity can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Seven of nine ICANS events (78%) were concurrent with CRS (during or within 7 days of CRS resolution). The median time to onset of ICANS was 4 (Range: 2 to 5) days after the most recent dose, with a median duration of 3 (Range: 1 to 20) days.
Patients treated with subcutaneous teclistamab monotherapy (N=238) in MajesTEC-1 were evaluated for antibodies to teclistamab using an electrochemiluminescence-based immunoassay. One subject (0.4%) developed neutralising antibodies to teclistamab of low-titre.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
