CRS, including life-threatening or fatal reactions, can occur in patients receiving TALVEY®1
In the clinical trial, CRS occurred in 76% of patients (N=339) who received TALVEY® at the recommended dosages
CRS was primarily Grade 1/2, with Grade 3 events occurring in 1.5% of patients
Recurrent CRS occurred in 30% of patients
Median time to onset: 27 hours (range: 0.1–167) from the last dose
Median duration: 17 hours (range: 0–622)
Incidence of CRS
Incidence of CRS
| CRS Experienced After Each Dose of TALVEY® (N=339) | |
|---|---|
| Q2W | QW |
| Step-up dosing schedule | |
| Step-up dose 1 29% | |
| Step-up dose 2 44% | |
| Step-up dose 3 (N=153) 33% | First treatment dose 30% |
| First treatment dose 12% | N/A |
| Dosing after step-up schedule | |
| Each remaining dose in Cycle 1 <3% | |
| Cumulatively from Cycle 2 onwards <3% | |
TALVEY® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS) Program. Visit TEC-TALREMS.com.Visit TEC-TALREMS.com.
CRS, cytokine release syndrome; N/A, not applicable; QW, once weekly; Q2W, every 2 weeks.
- TALVEY® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
Neurologic toxicity, including ICANS, and serious and life-threatening or fatal reactions, can occur with TALVEY®1
Neurologic toxicity, including ICANS, occurred in 55% of patients at the recommended dosages
Grade 3/4 events occurred in 6% of patients
Most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction (10%)
ICANS was reported in 9% of 265 patients where ICANS was collected and who received TALVEY® at the recommended dosages
Recurrent ICANS occurred in 3% of patients
ICANS can occur concurrently with CRS, following resolution of CRS, or in the absence of CRS
Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia
Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule and in the event of new onset of any neurological symptoms, until symptoms resolve
Median time to onset: 2.5 days (range: 1–16) from the last dose
Median duration: 2 days (range: 1–22)
| ICANS Experienced After Each Dose of TALVEY® (N=265) | |
|---|---|
| Q2W | QW |
| Step-up dosing schedule | |
| Step-up dose 1 3% | |
| Step-up dose 2 3% | |
| Step-up dose 3 1.8% | First treatment dose (N=156) 2.6% |
| First treatment dose (N=109) 3.7% | N/A |
TALVEY® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS) Program. Visit TEC-TALREMS.com.Visit TEC-TALREMS.com.
CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; N/A, not applicable; QW, once weekly; Q2W, every 2 weeks.
- TALVEY® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
Safety profile in the primary analysis population1
Adverse reactions (≥10%) in patients with relapsed or refractory multiple myeloma who received TALVEY® in MonumenTAL-1
| System Organ Class Adverse Reaction | TALVEY® (N=339) | |
|---|---|---|
| Any Grade (%) | Grade 3 or 4 (%) | |
| General disorders and administration site conditions | ||
| Pyrexia* | 83 | 4.7† |
| Fatigue* | 37 | 3.5† |
| Chills | 19 | 0 |
| Pain* | 18 | 1.8† |
| Edema* | 14 | 0 |
| Injection site reaction* | 13 | 0 |
| Immune system disorders | ||
| Cytokine release syndrome | 76 | 1.5† |
| Gastrointestinal disorders | ||
| Dysgeusiaठ| 70 | 0 |
| Dry mouth‡ | 34 | 0 |
| Dysphagia | 23 | 0.9† |
| Diarrhea | 21 | 0.9† |
| Stomatitisǁ | 18 | 1.2† |
| Nausea | 18 | 0 |
| Constipation | 16 | 0 |
| Oral disorder¶ | 12 | 0 |
| Skin and subcutaneous tissue disorders | ||
| Nail disorder# | 50 | 0 |
| Skin disorder** | 41 | 0.3† |
| Rash†† | 38 | 3.5† |
| Xerosis‡‡ | 30 | 0 |
| Pruritus | 19 | 0.3† |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal pain* | 43 | 3.2† |
| Investigations | ||
| Weight decreased | 35 | 1.5† |
| Infections and infestations | ||
| Upper respiratory tract infection* | 22 | 2.7† |
| Bacterial infection including sepsis§§ǁǁ | 19 | 9 |
| COVID-19*§§ | 11 | 2.7 |
| Fungal infection§§¶¶ | 10 | 0.6 |
| Vascular disorders | ||
| Hypotension* | 21 | 2.9 |
| Nervous system disorders | ||
| Headache* | 21 | 0.6† |
| Encephalopathy## | 15 | 1.8† |
| Sensory neuropathy*** | 14 | 0 |
| Motor dysfunction††† | 10 | 0.6† |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 19 | 1.2† |
| Respiratory, thoracic, and mediastinal disorders | ||
| Cough* | 17 | 0 |
| Dyspnea*§§ | 11 | 1.8 |
| Hypoxia* | 10 | 1.5† |
| Cardiac disorders | ||
| Tachycardia* | 11 | 0.6† |
Clinically relevant adverse reactions reported in <10% of patients who received TALVEY® included ICANS and viral infection.
Serious adverse reactions occurred in 47% of patients who received TALVEY®. Serious adverse reactions reported in ≥2% of patients included CRS (13%), bacterial infection (8%) including sepsis, pyrexia (4.7%), ICANS (3.8%), COVID-19 (2.7%), neutropenia (2.1%), and upper respiratory tract infection (2.1%).
Fatal adverse reactions occurred in 3.2% of patients who received TALVEY®, including COVID-19 (0.6%), dyspnea (0.6%), general physical health deterioration (0.6%), bacterial infection (0.3%) including sepsis, basilar artery occlusion (0.3%), fungal infection (0.3%), infection (0.3%), and pulmonary embolism (0.3%).
Dosage interruptions of TALVEY® due to an adverse reaction occurred in 56% of patients. Adverse reactions which required dosage interruption in >5% of patients included pyrexia (15%), CRS (12%), upper respiratory tract infection (9%), COVID-19 (9%), bacterial infection (7%) including sepsis, neutropenia (6%), and rash (6%).
The most common adverse reactions (≥20%) were pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.
Laboratory abnormalities
The most common Grade 3 or 4 laboratory abnormalities (≥30%) were lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.
Permanent discontinuation of TALVEY® due to an adverse reaction occurred in 9% of patients.
Adverse reactions which resulted in permanent discontinuation of TALVEY® in >1% of patients included ICANS.
Duration of exposure for Q2W was 3.7 months (range: 0.0-17.9) (N=153) and for QW was 5.9 months (range: 0.0-25.3) (N=186).
Note: Adverse reactions were graded based on CTCAE version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria.
*Includes other related terms.
Only Grade 3 adverse reactions occurred.
Per CTCAE version 4.03, maximum toxicity grade for dysgeusia is 2 and maximum toxicity grade for dry mouth is 3.
Dysgeusia: ageusia, dysgeusia, hypogeusia and taste disorder.
Stomatitis: cheilitis, glossitis, glossodynia, mouth ulceration, oral discomfort, oral mucosal erythema, oral pain, stomatitis, swollen tongue, tongue discomfort, tongue erythema, tongue edema, and tongue ulceration.
Oral disorder: oral disorder, oral dysesthesia, oral mucosal exfoliation, oral toxicity, and oropharyngeal pain.
Nail disorder: koilonychia, nail bed disorder, nail cuticle fissure, nail discoloration, nail disorder, nail dystrophy, nail hypertrophy, nail pitting, nail ridging, nail toxicity, onychoclasis, onycholysis, and onychomadesis.
Skin disorder: palmar-plantar erythrodysesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation, and skin fissures.
Rash: dermatitis, dermatitis acneiform, dermatitis contact, dermatitis exfoliative, dermatitis exfoliative generalized, erythema, exfoliative rash, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, rash vesicular, and stasis dermatitis.
Xerosis: dry eye, dry skin, and xerosis.
Includes fatal outcome(s): COVID-19 (N=2), dyspnea (N=2), bacterial infection including sepsis (N=1), fungal infection (N=1).
Bacterial infection: campylobacter infection, carbuncle, cellulitis, citrobacter infection, clostridium difficile colitis, clostridium difficile infection, cystitis escherichia, cystitis klebsiella, diverticulitis, escherichia pyelonephritis, folliculitis, gastroenteritis escherichia coli, helicobacter gastritis, human ehrlichiosis, impetigo, klebsiella sepsis, moraxella infection, otitis media acute, pitted keratolysis, pseudomonal bacteremia, pyuria, relapsing fever, renal abscess, skin infection, staphylococcal infection, tooth abscess, tooth infection, urinary tract infection enterococcal, and urinary tract infection pseudomonal.
Fungal infection: body tinea, candida infection, fungal foot infection, fungal infection, fungal skin infection, genital candidiasis, esophageal candidiasis, onychomycosis, oral candidiasis, oral fungal infection, oropharyngeal candidiasis, tinea pedis, vulvovaginal candidiasis, and vulvovaginal mycotic infection.
Encephalopathy: agitation, altered state of consciousness, amnesia, aphasia, bradyphrenia, confusional state, delirium, depressed level of consciousness, disorientation, encephalopathy, hallucination, lethargy, memory impairment, mood altered, restlessness, sleep disorder, and somnolence.
Sensory neuropathy: dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, immune-mediated neuropathy, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sciatica, and vestibular neuronitis.
Motor dysfunction: dysarthria, dysgraphia, dysmetria, dysphonia, gait disturbance, muscle atrophy, muscle spasms, muscular weakness, and tremor.
ASTCT, American Society for Transplantation and Cellular Therapy; COVID, coronavirus disease; CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; ICANS, immune effector cell-associated neurotoxicity syndrome; QW, once weekly; Q2W, every 2 weeks.
- TALVEY® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
Onset and management guidance for select adverse reactions1
ORAL TOXICITY
TALVEY® can cause oral toxicities
80%
of patients experienced an oral toxicity
- Grade 3 occurred in 2.1% of patients who received TALVEY® at the recommended dosages
- The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%)
Median time to onset and resolution based on clinical trial data
The median time to onset was 15 days in the clinical trial (range: 1–634 days)
The median time to resolution was 43 days in the clinical trial (range: 1–530 days)
65%
of patients
had oral toxicity that did not resolve to baseline
WEIGHT LOSS
TALVEY® can cause weight loss
62%
of patients experienced weight loss*
with 29% experiencing Grade 2 (>10%) weight loss and 2.7% experiencing Grade 3 (>20%) weight loss
Median time to onset and resolution based on clinical trial data
The median time to onset of Grade 2 or higher was 67 days (~2.2 months) in the clinical trial (range: 6–407 days)1,2
The median time to resolution was 50 days (~1.6 months) in the clinical trial (range: 1–403 days)1,2
57%
of patients
did not have their weight loss resolve
*62% of patients experienced weight loss, regardless of having an oral toxicity.
SKIN TOXICITY
TALVEY® can cause serious skin reactions
62%
of patients experienced skin reactions
- Skin reactions included rash, maculo-papular rash, erythema, and erythematous rash
- Grade 3 skin reactions occurred in 0.3% of patients
Median time to onset and resolution based on clinical trial data
The median time to onset was 25 days in the clinical trial (range: 1–630 days)
The median time to improvement to Grade 1 or less was 33 days in the clinical trial
*The median time to improvement to Grade 1 or less was 33 days.
- TALVEY® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
- Data on file. Janssen Biotech, Inc.