SAFETY FROM THE MajesTEC-1 TRIAL1

MajesTEC‑1 Primary Safety Analysis

Among patients who received TECVAYLI®, 47% were exposed for 6 months or longer and 7% were exposed for one year or longer.

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%).1

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%).1

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.1

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‑19.1

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)].1

Please see Table 11 in the full Prescribing Information for a summary of laboratory abnormalities in MajesTEC‑1.1

Adverse reactions (≥10%) in patients with RRMM treated with TECVAYLI® in the MajesTEC-1 trial primary analysis1

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Table with system organ class and adverse reactions when receiving TECVAYLI™

ASTCT, American Society for Transplantation and Cellular Therapy; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; RRMM, relapsed or refractory multiple myeloma.

Adverse reactions were graded based on CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria.

*Injection site reaction includes application site erythema, injection site bruising, injection site cellulitis, injection site discomfort, injection site erythema, injection site hematoma, injection site induration, injection site inflammation, injection site edema, injection site pruritus, injection site rash, injection site reaction and injection site swelling.

†Fatigue includes asthenia and fatigue.

‡Pain includes ear pain, flank pain, groin pain, oropharyngeal pain, pain, pain in jaw, toothache and tumor pain.

§Edema includes face edema, fluid overload, fluid retention, edema peripheral and peripheral swelling.

Hypogammaglobulinemia includes hypogammaglobulinemia and hypoglobulinemia.

#Musculoskeletal pain includes arthralgia, back pain, muscle discomfort, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain and pain in extremity.

**Upper respiratory tract infection includes bronchitis, influenza like illness, nasopharyngitis, pharyngitis, respiratory tract infection, respiratory tract infection bacterial, rhinitis, rhinovirus infection, sinusitis, tracheitis, upper respiratory tract infection and viral upper respiratory tract infection.

††Pneumonia includes COVID-19 pneumonia, enterobacter pneumonia, lower respiratory tract infection, metapneumovirus pneumonia, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia klebsiella, pneumonia moraxella, pneumonia pneumococcal, pneumonia pseudomonal, pneumonia respiratory syncytial viral, pneumonia staphylococcal and pneumonia viral.

‡‡Urinary tract infection includes cystitis, cystitis escherichia, cystitis klebsiella, escherichia urinary tract infection, urinary tract infection and urinary tract infection bacterial.

§§Motor dysfunction includes cogwheel rigidity, dysgraphia, dysphonia, gait disturbance, hypokinesia, muscle rigidity, muscle spasms, muscular weakness, peroneal nerve palsy, psychomotor hyperactivity, tremor and VIth nerve paralysis.

¶¶Sensory neuropathy includes dysesthesia, hypoesthesia, hypoesthesia oral, neuralgia, paresthesia, paresthesia oral, peripheral sensory neuropathy, sciatica and vestibular neuronitis.

##Encephalopathy includes agitation, apathy, aphasia, confusional state, delirium, depressed level of consciousness, disorientation, dyscalculia, hallucination, lethargy, memory impairment, mental status changes and somnolence.

***Hemorrhage includes conjunctival hemorrhage, epistaxis, hematoma, hematuria, hemoperitoneum, hemorrhoidal hemorrhage, lower gastrointestinal hemorrhage, melena, mouth hemorrhage and subdural hematoma.

†††Hypertension includes essential hypertension and hypertension.

‡‡‡Cough includes allergic cough, cough, productive cough and upper-airway cough syndrome.

§§§Cardiac arrhythmia includes atrial flutter, cardiac arrest, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, tachycardia and ventricular tachycardia.

¶¶¶Acute kidney injury includes acute kidney injury and renal impairment.

###Only Grade 3 adverse reactions occurred.

****Includes the following fatal adverse reactions: hemorrhage (n=1), pneumonia (n=3).

Dose reductions are not recommended with TECVAYLI®1

Dose interruptions of TECVAYLI® due to adverse reactions occurred in 73% of patients, and the most frequent (>5%) leading to dose interruptions were:

  • Neutropenia
  • Pneumonia
  • Pyrexia
  • CRS
  • Upper respiratory tract infection
  • COVID-19

Dosage delays may be required to manage toxicities related to TECVAYLI®.

Permanent discontinuation of TECVAYLI® due to adverse reactions occurred in 1.2% of patients in the primary analysis1

  • The adverse reactions resulting in permanent discontinuation of TECVAYLI® included pneumonia (adenoviral and pneumocystis jirovecii pneumonia in the same patient) and hypercalcemia

See the recommended dose modifications for TECVAYLI®

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Discontinuation rates due to adverse reactions in MajesTEC‑112

Primary Analysis Pie Chart

Adverse reactions resulting in permanent discontinuation of TECVAYLI® were pneumonia (adenoviral and pneumocystis jirovecii pneumonia in the same patient) and hypercalcemia.

Followup Pie Chart

Adverse reactions resulting in permanent discontinuation of TECVAYLI® were COVID-19 in 2 patients; progressive multifocal leukoencephalopathy, sepsis, arthralgia, arthritis, and brain neoplasm in 1 patient each; and events of pneumocystis jirovecii pneumonia and pneumonia adenoviral in the same patient, and hypercalcemia.

*This informations is not included in the current full Prescribing Information.

CRS, including life-threatening or fatal reactions, may occur in patients receiving TECVAYLI®1

  • CRS of any grade was reported in 72% of patients receiving TECVAYLI® in the primary analysis

Median time to onset: 2 days (range: 1-6 days) after most recent dose

Median duration: 2 days (range: 1-9 days)

Incidence of cytokine release syndrome (crs) chartIncidence of cytokine release syndrome (crs) chart

CRS experienced after specific dose of TECVAYLI® in the primary analysis

Cytokine release syndrome (crs) experiences by step-up dosing chartCytokine release syndrome (crs) experiences by step-up dosing chart
  • Recurrent CRS occurred in 33% of patients

Signs and symptoms of CRS may include:

  • Fever
  • Hypoxia
  • Chills
  • Hypotension
  • Sinus tachycardia
  • Headache
  • Elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation)

If not already hospitalized, at the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI® based on severity.

TECVAYLI® is available only through a restricted program under a REMS.

Patient counseling

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

Discuss the signs and symptoms associated with CRS, including fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes. Advise patients to immediately contact their healthcare provider if they experience signs or symptoms of CRS.

  • Fever (100.4°F or higher)
  • Feeling anxious
  • Difficulty breathing
  • Confusion or restlessness
  • Chills
  • Headache
  • Dizziness or lightheadedness
  • Increased liver enzymes in their blood
  • Fast heartbeat

Advise patients that they will be hospitalized for 48 hours after administration of all doses within the TECVAYLI® step-up dosing schedule.

Serious or life-threatening neurologic toxicities, including ICANS, may occur following treatment with TECVAYLI®1

In the primary analysis, neurologic toxicities were reported in 57% of patients receiving TECVAYLI® at the recommended dose.

  • The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%)
  • With longer follow-up, 1 patient experienced Grade 4 seizure and 1 patient experienced fatal Guillain-Barré syndrome
  • Grade 3 and Grade 4 neurologic toxicity events (2.4%) have been observed in patients treated with TECVAYLI®

Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity.

Immune effector cell-associated neurotoxicity syndrome (ICANS)

In the primary analysis, ICANS was reported in 6% of patients receiving TECVAYLI® at the recommended dose.

  • Recurrent ICANS occurred in 1.8% of patients
  • The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia
  • 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

ICANS experienced after specific dose of TECVAYLI® in the primary analysis

Step-up dosing tableStep-up dosing table

Median time to onset: 4 days (range: 2-8)

Median duration: 3 days (range: 1-20)

The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

TECVAYLI® is available only through a restricted program under a Risk
Evaluation and Mitigation Strategy (REMS)
called TECVAYLI® and
TALVEY® REMS. 
Visit TEC-TALREMS.com

Patient counseling

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

Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, including headache, confusion, dysgraphia, motor dysfunction, neuropathy, or encephalopathy. Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity. 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.

Symptoms of neurologic problems with TECVAYLI® include:

  • Headache
  • Jerking movements
  • Rigid muscles
  • Feeling restless
  • Numbness and tingling (feeling like “pins and needles”)
  • Confusion
  • Trouble speaking
  • Muscle spasms
  • Tremor
  • Double vision
  • Changes in your handwriting
  • Problems walking
  • Muscle weakness in your body or face
  • Hearing loss
  • Burning, throbbing, or stabbing pain

Advise patients that they will be hospitalized for 48 hours after administration of all doses within the TECVAYLI® step-up dosing schedule.

Use in specific populations in the MajesTEC-1 trial1

Pregnancy Based on the mechanism of action, TECVAYLI® may cause fetal harm when administered to a pregnant woman to evaluate for a drug associated risk. There are no available data on the use of TECVAYLI® in pregnant women 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.

Lactation There are no data on the presence of teclistamab-cqyv in human milk, the effect on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to TECVAYLI® are unknown. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with TECVAYLI® and for 5 months after the last dose.

Females and Males of Reproductive Potential TECVAYLI® may cause fetal harm when administered to a pregnant woman.

  • Pregnancy Testing: Verify pregnancy status of females of reproductive potential prior to initiating TECVAYLI®
  • Contraception (females): Advise females of reproductive potential to use effective contraception during treatment and for 5 months after the last dose of TECVAYLI®

Pediatric Use The safety and efficacy of TECVAYLI® have not been established in pediatric patients.

Geriatric Use Of the 165 patients with relapsed or refractory multiple myeloma treated with TECVAYLI® in MajesTEC-1 at the recommended dosage, 48% were 65 years of age or older, and 15% were 75 years of age or older. No overall differences in safety or effectiveness were observed between patients 65 to 74 years of age compared to younger patients. There is an insufficient number of patients 75 years of age or older to assess whether there are differences in safety or effectiveness.

MajesTEC-1 final safety analysis at 30.4 months2

You are now viewing a subsequent follow-up analysis of the MajesTEC-1 trial. This information is not included in the current full Prescribing Information.

At the time of the follow-up report, 38/165 (23%) of subjects were still on treatment

Reported since end of primary analysis:

  • One patient experienced 2 recurrent CRS events after a treatment delay
  • No additional events of ICANS

Reported since study initiation:

  • Eight treatment-related deaths occurred (4 due to COVID-19)
  • Permanent discontinuation due to adverse reactions occurred in 5.5% of patients

Treatment-emergent adverse events ≥20 at a median follow-up of 30.4 months

Adverse reactionsAdverse reactions

Discontinuation rates due to adverse reactions in MajesTEC‑11-3

Primary Analysis

Primary Analysis Pie Chart

Adverse reactions resulting in permanent discontinuation of TECVAYLI® were pneumonia (adenoviral and pneumocystis jirovecii pneumonia in the same patient) and hypercalcemia.

Final Analysis*

Followup Pie Chart

Adverse reactions resulting in permanent discontinuation of TECVAYLI® were COVID-19 in 2 patients; progressive multifocal leukoencephalopathy, sepsis, arthralgia, arthritis, and brain neoplasm in 1 patient each; and events of pneumocystis jirovecii pneumonia and pneumonia adenoviral in the same patient, and hypercalcemia.

*This informations is not included in the current full Prescribing Information.

AR, adverse reaction; COVID-19, coronavirus disease 2019; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; TEAE, treatment-emergent adverse event.

References:

  1. TECVAYLI® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  2. Data on file. Janssen Biotech, Inc.
  3. Garfall AL, Nooka AK, Niels WCJ van de Donk, et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. Poster. Presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2024; Chicago, IL.
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