Tecvayli Drug Information
Generic name: TECLISTAMAB-CQYV
Uses of Tecvayli
is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma in combination with daratumumab and hyaluronidase-fihj in patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. TECVAYLI is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma: in combination with daratumumab and hyaluronidase-fihj in patients who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. as monotherapy, in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
Dosage & Administration of Tecvayli
| N/A | ||
| Day 1 | ||
| Day 3 | Step-up dose 2 (0.3 mg/kg) | |
| Day 7 | First treatment dose (1.5 mg/kg) | |
| Weeks 2 to 8 | ||
| Weeks 9 to 24 | ||
| Week 25 onwards |
Side Effects of Tecvayli
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Relapsed/Refractory Multiple Myeloma In Combination with Daratumumab and Hyaluronidase-fihj The safety of TECVAYLI in combination with daratumumab and hyaluronidase-fihj (N=283) compared with either daratumumab and hyaluronidase-fihj, pomalidomide and dexamethasone (DPd) or daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) (N=290) was evaluated in patients with relapsed or refractory multiple myeloma in MajesTEC-3 . Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg once weekly, followed by TECVAYLI 3 mg/kg every two weeks, followed by TECVAYLI 3 mg/kg every four weeks, subcutaneously. Among patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj the median exposure was 32 (range 0.03 to 43) months.
Among patients who received DPd or DVd the median exposure was 16 (range 0.03 to 45) months. Serious adverse reactions occurred in 71% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj. Serious adverse reactions reported in ≥3% of patients included pneumonia (33%), upper respiratory tract infection (15%), cytokine release syndrome (10%), COVID-19 (7%), sepsis (6%), second primary malignancy (5%), pyrexia (4.9%), febrile neutropenia (4.6%), and gastroenteritis (4.2%). Fatal adverse reactions occurred in 2.5% of patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj, and included sepsis (0.7%), pneumonia (0.4%), sudden death (0.4%), myocardial infarction (0.4%), enterovirus myocarditis (0.4%) and hemophagocytic lymphohistiocytosis (0.4%). Permanent discontinuation of TECVAYLI due to adverse reactions occurred in 6% of patients.
Adverse reactions leading to discontinuation of TECVAYLI in more than one patient were pneumonia (1.1%), diarrhea (0.7%), fatigue (0.7%), second primary malignancy (0.7%), upper respiratory tract infection (0.7%) and cough (0.7%). Dosage interruptions of TECVAYLI due to an adverse reaction occurred in 94% of patients. Adverse reactions which required dosage interruption of TECVAYLI in ≥5% of patients included neutropenia (53%), upper respiratory tract infection (48%), COVID-19 (34%), pneumonia (34%), thrombocytopenia (14%), cytokine release syndrome (13%), gastroenteritis (10%), cough (10%), pyrexia (8%), diarrhea (7%), sepsis (6%) and fatigue (5%). The most common adverse reactions (≥20%) were hypogammaglobulinemia, upper respiratory tract infection, cytokine release syndrome, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and weight decreased. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells and decreased platelets.
Table 12 summarizes the adverse reactions in MajesTEC-3. Table 12: Adverse Reactions (≥10%) in Patients with Multiple Myeloma Who Received TECVAYLI in Combination with Daratumumab and Hyaluronidase-fihj in MajesTEC-3 Adverse Reaction TECVAYLI with daratumumab and hyaluronidase-fihj (N=283) DPd or DVd (N=290) Any Grade (%) Grade 3 or 4 (%) Any Grade (%) Grade 3 or 4 (%) DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone. Adverse reactions were graded according to NCI-CTCAE Version 5.0, with the exception of ICANS and CRS, which were graded by ASTCT 2019 consensus grading system; adverse reactions that were considered symptoms of CRS or ICANS were not included. Immune system disorders Hypogammaglobulinemia Hypogammaglobulinemia includes hypogammaglobulinemia, hypoglobulinemia; and/or patients with laboratory IgG levels below 400 mg/dL following treatment with TECVAYLI. 84 6 60
Cytokine release syndrome 60 0 0 0 Infections Upper respiratory tract infection
Upper respiratory tract infection includes bronchitis, bronchiolitis, pharyngitis, rhinitis, sinusitis, sinobronchitis, tracheitis, and tracheobronchitis and other related terms. 79 17 62 13 COVID-19 Includes other related terms. 45 6 33
Pneumonia Pneumonia includes atypical pneumonia, bacterial pneumonia, fungal pneumonia, viral pneumonia, and
other related terms. Includes the following fatal adverse reactions: Tec-Dara: Pneumonia (n=1); DPd/DVd: Pneumonia (n=2). 42 33 35 28 Gastroenteritis 20 4.9 8
Urinary tract infection 17 2.8 13 1 Herpes virus infection 11 2.1
6
Respiratory, thoracic and mediastinal disorders Cough 53 0.7 24 0 Dyspnea 13
1.8 20
Gastrointestinal disorders Diarrhea 52 3.9 31 2.4 Nausea 23 0 12 0.3
Vomiting 17 0 7 0 Abdominal pain 16 0.7 13 0 Constipation 14 0 20
Musculoskeletal and connective tissue disorders Musculoskeletal pain 50 1.4 47 4.5 General
disorders and administration site conditions Injection site reaction Includes injection site reactions related to teclistamab, daratumumab and hyaluronidase-fihj, or bortezomib. 41 0 4.5 0 Fatigue 39 3.9 40
Pyrexia 37 1.4 19 0.3 Edema 13 0.4 22 0.3 Nervous system
disorders Headache 26 1.4 12
Sensory neuropathy Sensory neuropathy includes dysaesthesia, hyperaesthesia, hypoaesthesia, paraesthesia, neuralgia, peripheral neuropathy
polyneuropathy, sciatica and other related terms. 17 0.7 25
Motor dysfunction Motor dysfunction includes balance disorder, dysarthria, dysphonia, gait disturbance, muscle
contracture, muscle spasms, muscle spasticity, muscle twitching, muscular weakness, myopathy, peripheral motor neuropathy, tremor and other related terms. 14 0 30 1 Investigations Weight decreased 20 2.8 7
Metabolism and nutrition disorders Decreased appetite 19 1.1 7 0 Cardiac disorders
Cardiac arrhythmia 11 1.1 8
Neoplasms Second primary malignancy 11 4.6 9 4.8 Vascular disorders Hypertension 11
4.6 6
Clinically relevant adverse reactions in <10% of patients who received
TECVAYLI in combination with daratumumab and hyaluronidase-fihj included sepsis, encephalopathy, CMV infection, febrile neutropenia and ICANS. Table 13 summarizes laboratory abnormalities in MajesTEC-3. Table 13: Select Laboratory Abnormalities (≥30%) that Worsened from Baseline in Patients with Multiple Myeloma who Received TECVAYLI in Combination with Daratumumab and Hyaluronidase-fihj in MajesTEC-3 Laboratory Abnormality TECVAYLI with daratumumab and hyaluronidase-fihj (N=283) DPd or DVd (N=290) All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone. Percentages calculated with the number of subjects with a baseline and at least one post-treatment value for each lab test as denominator. Laboratory toxicity grades are derived based on NCI CTCAE Version 5.0. The denominator used to calculate the incidence varied from 137 to 282 in Tec-Dara and 135 to 289 in DPd/DVd based on the number of patients with a baseline value and at least one post-treatment value.
Hematology Lymphocyte Count Decreased 99 95 93 64 White Blood Cell Decreased 94 60 96 74 Neutrophil Count Decreased 91 78 94 84 Platelet Count Decreased 73 21 72 25 Hemoglobin Decreased 64 17 61 19 Chemistry Alanine Aminotransferase Increased 60 5 33
Aspartate Aminotransferase Increased 55 3.9 22 1.7 Potassium Decreased 52 15 35
8 GGT Increased 51 5 24 0 Sodium Decreased 46 10 37 6 Lipase Increased 49 18 21
Serum Amylase Increased 31 7 13 0 Monotherapy
The safety of TECVAYLI monotherapy (N=165) in patients with relapsed or refractory multiple myeloma was evaluated in MajesTEC-1 . Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg, subcutaneously once weekly. Among patients who received TECVAYLI, 47% were exposed for 6 months or longer and 7% were exposed for one year or longer. The median age of patients who received TECVAYLI was 64 years (range: 33 to 84 years); 58% were male; 81% were White, 13% were Black or African American, and 2% were Asian.
Serious adverse reactions occurred in 54% of patients who received TECVAYLI. Serious adverse reactions in >2% of patients included pneumonia (15%), cytokine release syndrome (8%), sepsis (6%), general physical health deterioration (6%), COVID-19 (6%), acute kidney injury (4.8%), pyrexia (4.8%), musculoskeletal pain (2.4%), and encephalopathy (2.4%). Fatal adverse reactions occurred in 5% of patients who received TECVAYLI, including COVID-19 (1.8%), pneumonia (1.8%), septic shock (0.6%), acute renal failure (0.6%), and hemoperitoneum (0.6%). Permanent discontinuation of TECVAYLI due to adverse reactions occurred in 1.2% of patients. Adverse reactions resulting in permanent discontinuation of TECVAYLI included pneumonia (adenoviral and pneumocystis jirovecii pneumonia in the same patient) and hypercalcemia. Dosage interruptions of TECVAYLI due to an adverse reaction occurred in 73% of patients.
Adverse reactions which required dosage interruption in >5% of patients included neutropenia, pneumonia, pyrexia, cytokine release syndrome, upper respiratory tract infection, and COVID-19. The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets. Table 14 summarizes the adverse reactions in MajesTEC-1. Table 14: Adverse Reactions (≥10%) in Patients with Multiple Myeloma Who Received TECVAYLI in MajesTEC-1 Adverse Reactions TECVAYLI (N=165) Any Grade (%) Grade 3 or 4 (%) Adverse reactions were graded based on NCI-CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria.
General disorders and administration site conditions Pyrexia 76 3 Only grade 3 adverse reactions occurred. Injection site reaction Includes other related terms. 37
Fatigue 33 2.4 Chills 16 0 Pain 15 1.8 Edema 13 0
Immune system disorders Cytokine release syndrome 72
Hypogammaglobulinemia Hypogammaglobulinemia includes hypogammaglobulinemia and hypoglobulinemia. 11 1.2 Musculoskeletal and connective tissue
disorders Musculoskeletal pain 44
Bone pain 16 3 Infections Upper respiratory tract infection Upper respiratory tract
infection includes bronchitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, tracheitis and other related terms. 26
Pneumonia Pneumonia includes bacterial pneumonia, viral pneumonia, and other related terms. Includes
the following fatal adverse reactions: hemorrhage (n=1), pneumonia (n=3). 24 15 Urinary tract infection 11 5 Gastrointestinal disorders Nausea 25
Diarrhea 21 2.4 Constipation 18 0 Vomiting 12 0.6 Nervous system disorders
Headache 25
Motor dysfunction Motor dysfunction includes cogwheel rigidity, dysgraphia, dysphonia, gait disturbance, hypokinesia
muscle rigidity, muscle spasms, muscular weakness, peroneal nerve palsy, psychomotor hyperactivity, tremor and VI th nerve paralysis. 16 0 Sensory neuropathy Sensory neuropathy includes dysesthesia, hypoesthesia, hypoesthesia oral, neuralgia, paresthesia, paresthesia oral, peripheral sensory neuropathy, sciatica and vestibular neuronitis. 15
Encephalopathy Encephalopathy includes agitation, apathy, aphasia, confusional state, delirium, depressed level of
consciousness, disorientation, dyscalculia, hallucination, lethargy, memory impairment, mental status changes and somnolence. 13 0 Vascular disorders Hypotension 18
Hemorrhage 12 1.8 Hypertension 12 4.8 Respiratory, thoracic, and mediastinal disorders Hypoxia
18
Cough 15 0 Cardiac disorders Cardiac arrhythmia 16 1.8 Metabolism and nutrition
disorders Decreased appetite 11
Renal and urinary disorders Acute kidney injury 11 3.6 Clinically relevant adverse
reactions in <10% of patients who received TECVAYLI included febrile neutropenia, sepsis, ICANS, seizure, Guillain-Barré syndrome, hepatic failure, and new onset or reactivated viral infections (including adenovirus, hepatitis B virus (HBV), cytomegalovirus (CMV), varicella zoster virus (VZV), herpes simplex virus (HSV), and progressive multifocal leukoencephalopathy (PML). Table 15 summarizes laboratory abnormalities in MajesTEC-1. Table 15: Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in TECVAYLI Treated Patients with Multiple Myeloma in MajesTEC-1 Laboratory Abnormality TECVAYLI (N=165 The denominator used to calculate the rate varied from 164 to 165 based on the number of patients with a baseline value and at least one post-treatment value. ) All Grades (%) Grade 3 or 4 (%) Laboratory toxicity grades are derived based on NCI CTCAE Version 4.03. Hematology Lymphocyte count decreased 92 84 White blood cell decreased 86 41 Neutrophil count decreased 84 56 Platelet count decreased 71 22 Hemoglobin decreased 67 33 Chemistry Albumin decreased 68 6 Alkaline phosphatase increased 42
Phosphorus decreased 38 13 Gamma-glutamyl transferase increased 37 8 Sodium decreased 35
10 Aspartate aminotransferase increased 34
Warnings & Cautions for Tecvayli
Cytokine Release Syndrome
TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions . In the clinical trials (monotherapy and combination therapy trials; N=448), CRS occurred in 64% of patients who received TECVAYLI at the recommended dosage, with Grade 1 CRS occurring in 46% of patients, Grade 2 in 18%, and Grade 3 in 0.2%. Recurrent CRS occurred in 27% of patients. Most patients experienced CRS during the initial step-up dosing schedule (step-up dose 1 (37%), step-up dose 2 (32%), or the initial treatment dose (20%)). CRS first occurred following subsequent doses of TECVAYLI in 2.5% of patients. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose and the median duration of CRS was 2 (range: 1 to 22) days.
Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation). Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS . Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly . At the first sign of CRS, immediately evaluate the patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold until CRS resolves or permanently discontinue TECVAYLI based on severity . TECVAYLI is available only through a restricted program under a REMS.
Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome
TECVAYLI can cause serious, life-threatening or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) . In the clinical trials (monotherapy and combination therapy trials; N=448), neurologic toxicity occurred in 60% of patients who received TECVAYLI at the recommended dosage, with Grade 3 or 4 neurologic toxicity in 6%. Neurologic toxicities reported in ≥5% of patients included headache (27%), sensory neuropathy (16%), motor dysfunction (15%), insomnia (12%), encephalopathy (11%), and dizziness (8%). Fatal neurologic toxicity occurred in 0.4% of patients, including Guillain-Barré syndrome and status epilepticus (one patient each). In MajesTEC-1, ICANS was reported in 6% of patients who received TECVAYLI as monotherapy at the recommended dosage . Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent TECVAYLI doses. The median time to onset of ICANS was 4 days (range: 2 to 8 days) after the most recent TECVAYLI dose with a median duration of 3 days (range: 1 to 20 days). The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia.
In MajesTEC-3, ICANS was reported in 1.1% of patients who received the recommended TECVAYLI dosage in combination with daratumumab and hyaluronidase-fihj, including Grade 4 ICANS in 1 patient. All events of ICANS occurred during the step-up dosing schedule . The median time to onset of ICANS was 2 days (range: 1 to 3 days) after the most recent dose and the median duration of ICANS was 2 days (range: 1 to 2 days). The clinical manifestations of ICANS reported were amnesia, encephalopathy and delirium. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS during TECVAYLI treatment.
At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold until neurologic toxicity resolves or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines . Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness . Advise patients to refrain from driving or 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 neurologic toxicity symptoms until neurologic toxicity resolves . TECVAYLI is available only through a restricted program under a REMS.
TECVAYLI and
TALVEY REMS TECVAYLI is available only through a restricted program under a REMS called the "TECVAYLI and TALVEY REMS" because of the risks of CRS and neurologic toxicity, including ICANS. Notable requirements of the TECVAYLI and TALVEY REMS include the following: Prescribers must be certified with the REMS by enrolling and completing training. Prescribers must counsel patients receiving TECVAYLI about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with Patient Wallet Card. Pharmacies and healthcare settings that dispense TECVAYLI must be certified with this REMS and must verify prescribers are certified through this REMS. Wholesalers and distributers must only distribute TECVAYLI to certified pharmacies or healthcare settings.
Further information about the "TECVAYLI and TALVEY REMS" is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.
Hepatotoxicity
TECVAYLI can cause hepatotoxicity, including fatalities. There was one fatal case of hepatic failure in MajesTEC-1. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), elevated aspartate aminotransferase (AST) occurred in 47% of patients, with Grade 3 or 4 elevations in 2.9%. Elevated alanine aminotransferase (ALT) occurred in 48% of patients, with Grade 3 or 4 elevations in 3.8%. Elevated total bilirubin occurred in 10% of patients with Grade 3 or 4 elevations in 0.7%. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during TECVAYLI treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Infections
TECVAYLI can cause severe, life-threatening, or fatal infections. In MajesTEC-1 (N=165), in patients who received the recommended TECVAYLI dosage, serious infections, including opportunistic infections, occurred in 30% of patients, Grade 3 or 4 infections occurred in 35% of patients, and fatal infections occurred in 4.2% of patients . In MajesTEC-3 (N=283), in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj at the recommended dosage, serious infections, including opportunistic infections, occurred in 54% of patients, Grade 3 or Grade 4 infections occurred in 54% of patients and fatal infections occurred in 4.6% of patients . Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to current practice guidelines . Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity . Monitor immunoglobulin levels prior to and during treatment with TECVAYLI and administer subcutaneous or intravenous immunoglobulin (IVIG) to maintain the serum levels >400 mg/dL.
Neutropenia
TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), decreased neutrophils occurred in 88% of patients, with Grade 3 or 4 decreased neutrophils in 70%. Febrile neutropenia occurred in 6% of patients. Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines.
Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity .
Hypersensitivity and Other
Administration Reactions TECVAYLI can cause both systemic administration-related reactions and local injection-site reactions. Systemic Reactions In patients who received the recommended TECVAYLI dosage in the clinical trials (monotherapy and combination therapy trials; N=448), 2.5% of patients experienced systemic-administration reactions, which included recurrent pyrexia and rash. Local Reactions In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), injection-site reactions occurred in 37% of patients with Grade 1 injection-site reactions in 29% and Grade 2 in 9%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity .
Embryo-Fetal Toxicity
Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient. Advise pregnant patients of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose .
Drug Interactions with Tecvayli
causes release of cytokines that may suppress activity of certain cytochrome P450 (CYP) enzymes, resulting in increased exposure of CYP substrates, which may increase the risk of adverse reactions of the CYP substrates. The highest risk of drug-drug interaction is expected to occur after initiation of TECVAYLI step-up dosing schedule up to 7 days after the first treatment dose and during and after CRS . Monitor for toxicity and/or concentrations of CYP substrates where minimal increases in concentration may lead to serious adverse reactions. Consider decreasing the dosage of the concomitant CYP substrate as needed.
Certain CYP Substrates : Monitor for toxicity and/or concentrations of CYP substrates where minimal increases in concentration may lead to serious adverse reactions. Consider decreasing the dosage of the concomitant CYP substrate, as needed.
Pregnancy Safety for Tecvayli
Pregnancy Risk Summary Based on the mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient . There are no available data on the use of TECVAYLI in pregnant patients to evaluate for a drug associated risk. No animal reproductive or developmental toxicity studies have been conducted with TECVAYLI. Teclistamab-cqyv causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G (IgG) is known to cross the placenta; therefore, teclistamab-cqyv has the potential to be transmitted from the mother to the developing fetus.
Advise women of the potential risk to the fetus. TECVAYLI is associated with hypogammaglobulinemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with TECVAYLI should be considered. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Pediatric Use of Tecvayli
Pediatric Use The safety and efficacy of TECVAYLI have not been established in pediatric patients.
Clinical Studies of Tecvayli
Relapsed or Refractory Multiple Myeloma
In Combination with Daratumumab and Hyaluronidase - fihj The efficacy of TECVAYLI in combination with subcutaneous daratumumab and hyaluronidase-fihj compared with investigator's choice of either daratumumab and hyaluronidase-fihj, pomalidomide and dexamethasone (DPd) or daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) was evaluated in adult patients with relapsed or refractory multiple myeloma in a randomized, open-label, multi-center study (MajesTEC-3) (NCT05083169). The study included patients who had previously received one to three prior lines of therapy including a proteasome inhibitor and lenalidomide. Patients who had received only one prior line of therapy must have been refractory to lenalidomide. Patients who had disease refractory to a prior anti-CD38 monoclonal antibody therapy, or who had received any prior BCMA-directed therapy were excluded.
Patients received TECVAYLI in combination with daratumumab and hyaluronidase-fihj as follows: Subcutaneous TECVAYLI step-up doses of 0.06 mg/kg and 0.3 mg/kg, followed by TECVAYLI 1.5 mg/kg once weekly from Weeks 2 to 8, then 3 mg/kg every two weeks from Weeks 9 to 24, then 3 mg/kg every four weeks starting on Week 25 until disease progression or unacceptable toxicity, AND Subcutaneous daratumumab and hyaluronidase-fihj 1,800 mg/30,000 units (1,800 mg of daratumumab and 30,000 units of hyaluronidase) starting one day prior to TECVAYLI and continuing once weekly from Weeks 1 to 8, then every two weeks from Weeks 9 to 24, then every four weeks starting on Week 25 until disease progression or unacceptable toxicity . The major efficacy outcome measure was progression-free survival (PFS) by Independent Review Committee (IRC) assessment based on International Myeloma Working Group (IMWG) 2016 criteria. A total of 587 patients were randomized in MajesTEC-3: 291 to the TECVAYLI in combination with daratumumab and hyaluronidase-fihj group and 296 to the control group (DPd or DVd). The median age was 64 years (range: 25 to 88) with 38% aged 65 to 74 years and 10% aged 75 years or older; 55% were male; 65% were White, 6% were Black or African American, and 22% were Asian. The International Staging System (ISS) at screening was stage I in 63%, stage II in 29%, and stage III in 8%. High-risk cytogenetics (presence of del(17p), t(4;14) or t(14;16)) were present in 35% of patients.
Extramedullary disease was present in 5% of patients. The median number of prior lines of therapy was 2 (range: 1 to 3), with 38% who received one prior line of therapy. All patients received prior lenalidomide and 99.8% received a prior proteasome inhibitor; 84% were refractory to lenalidomide.
Seventy-four percent of patients previously received autologous stem cell transplantation. Five percent of patients received a prior anti-CD38 monoclonal antibody; there is limited data with TECVAYLI in combination with daratumumab and hyaluronidase-fihj in patients who have received or are refractory to prior anti-CD38 monoclonal antibody therapy. The trial demonstrated a statistically significant improvement in the TECVAYLI in combination with daratumumab and hyaluronidase-fihj group compared with the control group in PFS and overall survival (OS). The efficacy results are shown in Table 17 and Figures 1 and 2. Table 17: Efficacy Results (MajesTEC-3) TECVAYLI with daratumumab and hyaluronidase-fihj (N=291) DPd or DVd (N=296) DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone; CI=confidence interval; NE=not estimable; NR=not reached; MRD = minimal residual disease.
Progression-free survival (PFS) Based on intent-to-treat analysis set, Median duration of follow-up = 34.5 months Number of events, n (%) 44 187 Median, months (95% CI) NR (NE, NE)
Hazard ratio (95% CI) Stratified Cox proportional hazard model. For all stratified
analyses, stratification was based on ISS staging (I vs. II or III) and number of prior lines of therapy (1 vs. 2 or 3), as randomized ; p-value Stratified log-rank test 0.17 ; <0.0001 Overall survival (OS), Number of events, n (%) 46 98 Median, months (95% CI) NR (NE, NE) NR (41.4, NE) Hazard ratio (95% CI) ; p-value 0.46 ; <0.0001 Overall response (sCR+CR+VGPR+PR), n (%) 259 223 95% CI (%) p-value Stratified Cochran Mantel-Haenszel Chi-Squared test <0.0001 Stringent complete response (sCR), n (%) 225 69 Complete response (CR), n (%) 13 26 Very good partial response (VGPR), n (%) 14 74 Partial response (PR), n (%) 7 54 Complete response or better (sCR+CR), n (%) 238 95 95% CI (%) p-value <0.0001 MRD negativity rate Based on MRD next-generation sequencing (NGS) primary analysis set, defined as all randomized patients enrolled at sites where next generation sequencing assay was available., Based on a threshold of 10 -5 using a next generation sequencing assay (clonoSEQ)., N 262 269 n (%) 153 46 95% CI (%) p-value Fisher's exact test <0.0001 MRD negativity rate in patients with CR or better Number of patients with CR or better, n 216 86 MRD negativity rate, n (%) 153 46 95% CI (%) Figure 1: Kaplan-Meier Curve of PFS (MajesTEC-3) Tec-Dara = TECVAYLI in combination with daratumumab and hyaluronidase-fihj; DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone. Figure 2: Kaplan-Meier Curve of OS (MajesTEC-3) Tec-Dara = TECVAYLI in combination with daratumumab and hyaluronidase-fihj; DPd = daratumumab and hyaluronidase-fihj, pomalidomide, dexamethasone; DVd = daratumumab and hyaluronidase-fihj, bortezomib, dexamethasone.
In the 15 patients in MajesTEC-3 who had received a prior anti-CD38 monoclonal antibody, the ORR was 93.3% (95% CI: 68.1, 99.8). Monotherapy The efficacy of TECVAYLI was evaluated in patients with relapsed or refractory multiple myeloma in a single-arm, open-label, multi-center study (MajesTEC-1, NCT03145181 and NCT04557098 ). The study included patients who had previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The study excluded patients who had stroke, seizure, allogeneic stem cell transplantation within the past 6 months, Eastern Cooperative Oncology Group (ECOG) performance score of 2 or higher, known active CNS involvement or clinical signs of meningeal involvement of multiple myeloma, or active or documented history of autoimmune disease, with the exception of vitiligo, Type 1 diabetes, and prior autoimmune thyroiditis. Patients received step-up doses of 0.06 mg/kg and 0.3 mg/kg of TECVAYLI followed by TECVAYLI 1.5 mg/kg subcutaneously once weekly thereafter until disease progression or unacceptable toxicity . The efficacy population included 110 patients.
The median age was 66 (range: 33 to 82) years with 16% of patients 75 years of age or older; 56% were male; 91% were White, 5% were Black or African American, 3% were Asian. The International Staging System (ISS) at study entry was Stage I in 50%, Stage II in 38%, and Stage III in 12% of patients. High-risk cytogenetics (presence of del(17p), t(4;14) or t(14;16)) were present in 25% of patients.
Seventeen percent of patients had extramedullary plasmacytomas. Patients with prior BCMA-targeted therapy were not included in the efficacy population. The median number of prior lines of therapy was 5 (range: 2 to 14); 78% of patients had received at least 4 prior lines of therapy.
Eighty-one percent of patients received prior stem cell transplantation. All patients had received prior therapy with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and 76% were triple-class refractory (refractory to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody). Efficacy was established based on overall response rate (ORR) as determined by the Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) 2016 criteria (see Table 18 ). The median time to first response was 1.2 months (range: 0.2 to 5.5 months). With a median follow-up of 7.4 months among responders, the estimated duration of response (DOR) rate was 90.6% (95% CI: 80.3%, 95.7%) at 6 months and 66.5% (95% CI: 38.8%, 83.9%) at 9 months. Table 18: Efficacy Results for MajesTEC-1 N=110 NE=not estimable Overall response rate (ORR: sCR+CR+VGPR+PR) n (%) 68 95% CI (%) Complete response (CR) or better Complete response or better = Stringent complete response (sCR) + complete response (CR). 31 Very good partial response (VGPR) 32 Partial response (PR) 5 Duration of Response (DOR) (months) DOR (Months): Median (95% CI) NE (9.0, NE) Figure 1 Figure 2
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
Ready to save on Tecvayli?
Compare prescription prices at over 70,000 pharmacies and start saving today—no enrollment required.
Compare Tecvayli Prices