TALVEY

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY. Initiate TALVEY treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.2 , 2.5 ) , Warnings and Precautions (5.1) ] . Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life threatening or fatal reactions, can occur with TALVEY. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment and treat promptly. Withhold or permanently discontinue TALVEY based on severity [see Dosage and Administration (2.5) , Warnings and Precautions (5.2) ] . Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS) [see Warnings and Precautions (5.3) ] . WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME See full prescribing information for complete boxed warning. Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY. Initiate TALVEY treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY until CRS resolves or permanently discontinue based on severity. ( 2.2 , 2.5 , 5.1 ) Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threatening or fatal reactions, can occur in patients receiving TALVEY. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold or permanently discontinue TALVEY based on severity. ( 2.5 , 5.2 ) TALVEY is available only through a restricted program called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS). ( 5.3 )

5 WARNINGS AND PRECAUTIONS Oral Toxicity and Weight Loss : Monitor for oral toxicity and weight loss. Withhold or permanently discontinue based on severity. ( 5.4 ) Infections : Can cause serious, life-threatening, or fatal infections. Monitor for signs and symptoms of infection; treat appropriately. Withhold or consider permanent discontinuation based on severity. ( 5.5 ) Cytopenias : Monitor complete blood counts. ( 5.6 ) Skin Toxicity : Monitor for skin toxicity, including rash progression, for early intervention and treat appropriately. Withhold as recommended based on severity. ( 5.7 ) Hepatotoxicity: Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold or consider permanent discontinuation based on severity. ( 5.8 ) Embryo-Fetal Toxicity : May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) 5.1 Cytokine Release Syndrome (CRS) TALVEY can cause cytokine release syndrome, including life-threatening or fatal reactions [see Adverse Reactions (6.1) ] . In the clinical trial, CRS occurred in 76% of patients who received TALVEY at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (29%) or step-up dose 2 (44%) at the recommended dosages. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule (N=153). CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC). Initiate TALVEY therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY dose [see Dosage and Administration (2.2 , 2.3) ]. Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines. Withhold TALVEY until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.5) ] . TALVEY is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.2 Neurologic Toxicity including ICANS TALVEY can cause serious, life-threatening, or fatal neurologic toxicity, including ICANS [see Adverse Reactions (6.1) ] . In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received TALVEY at the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), and motor dysfunction, including ataxia/cerebellar ataxia (10%). ICANS was reported in 9% of 265 patients where ICANS was collected and who received TALVEY at the recommended dosages [see Adverse Reactions (6.1) ] . Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent 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. Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity; withhold or permanently discontinue TALVEY based on severity and consider further management per current practice guidelines [see Dosage and Administration (2.5) ]. Due to the potential for neurologic toxicity, patients receiving TALVEY are at risk of depressed level of consciousness. 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 [see Dosage and Administration (2.2) ] and in the event of new onset of any neurological symptoms, until symptoms resolve. TALVEY is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.3 TECVAYLI and TALVEY REMS TALVEY 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 [see Warnings and Precautions (5.1 , 5.2) ]. Notable requirements of the TECVAYLI and TALVEY REMS include the following: Prescribers must be certified with the program by enrolling and completing training. Prescribers must counsel patients receiving TALVEY about the risk of CRS and neurologic toxicity, including ICANS and provide patients with Patient Wallet Card. Pharmacies and healthcare settings that dispense TALVEY must be certified with the TECVAYLI and TALVEY REMS program and must verify prescribers are certified through the TECVAYLI and TALVEY REMS program. Wholesalers and distributers must only distribute TALVEY to certified pharmacies. Further information about the TECVAYLI and TALVEY REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064. 5.4 Oral Toxicity and Weight Loss TALVEY can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis [see Adverse Reactions (6.1) ] . In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring 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%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients. TALVEY can cause weight loss [see Adverse Reactions (6.1) ] . In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss. Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY or permanently discontinue based on severity [see Dosage and Administration (2.5) ] . 5.5 Infections TALVEY can cause serious infections, including life-threatening or fatal infections [see Adverse Reactions (6.1) ] . In the clinical trial, serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis, and COVID-19 (2.7%). Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanent discontinuation of TALVEY as recommended based on severity [see Dosage and Administration (2.5) ] . 5.6 Cytopenias TALVEY can cause cytopenias, including neutropenia and thrombocytopenia [see Adverse Reactions (6.1) ] . In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY as recommended based on severity [see Dosage and Administration (2.5) ] . 5.7 Skin Toxicity TALVEY can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash [see Adverse Reactions (6.1) ] . In the clinical trial, skin reactions occurred in 62% of patients, with Grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to Grade 1 or less was 33 days. Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold TALVEY as recommended based on severity [see Dosage and Administration (2.5) ] . 5.8 Hepatotoxicity TALVEY can cause hepatotoxicity. In the clinical trial, elevated ALT occurred in 33% of patients, with Grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with Grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients [see Adverse Reactions (6.1) ] . Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY or consider permanent discontinuation of TALVEY based on severity [see Dosage and Administration (2.5) ] . 5.9 Embryo-Fetal Toxicity Based on its mechanism of action, TALVEY may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY and for 3 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .

6 ADVERSE REACTIONS The following adverse reactions are also described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity, including ICANS [see Warnings and Precautions (5.2) ] Oral Toxicity and Weight Loss [see Warnings and Precautions (5.4) ] Infections [see Warnings and Precautions (5.5) ] Cytopenias [see Warnings and Precautions (5.6) ] Skin Toxicity [see Warnings and Precautions (5.7) ] Hepatotoxicity [see Warnings and Precautions (5.8) ] The most common adverse reactions (≥20%) are 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. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 MonumenTAL-1 The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma. Patients treated with the weekly dosing schedule received step-up doses of 0.01 mg/kg and 0.06 mg/kg of TALVEY followed by TALVEY 0.4 mg/kg subcutaneously weekly thereafter. Patients treated with the biweekly (every 2 weeks) dosing schedule received step-up doses of 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg (0.75 times the recommended step-up dose 3) followed by TALVEY 0.8 mg/kg subcutaneously every 2 weeks thereafter. The duration of exposure for the 0.4 mg/kg weekly regimen was 5.9 (range: 0.0 to 25.3) months (N=186) and for the 0.8 mg/kg biweekly (every 2 weeks) regimen, it was 3.7 (range: 0.0 to 17.9) months (N=153). Serious adverse reactions occurred in 47% of patients who received TALVEY. Serious adverse reactions 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%). 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. 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. The most common Grade 3 or 4 laboratory abnormalities (≥ 30%) were lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased. Table 13 summarizes the adverse reactions in MonumenTAL-1. Table 13: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1 TALVEY N=339 System Organ Class Adverse Reaction Any Grade (%) Grade 3 or 4 (%) Adverse reactions were graded based on CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria. General disorders and administration site conditions Pyrexia Includes other related terms. 83 4.7 Only grade 3 adverse reactions occurred. 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 Dysgeusia Dysgeusia: ageusia, dysgeusia, hypogeusia and taste disorder. Per CTCAE v4.03, maximum toxicity grade for dysgeusia is 2 and maximum toxicity grade for dry mouth is 3. 70 0 Dry mouth 34 0 Dysphagia 23 0.9 Diarrhea 21 0.9 Stomatitis 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. 18 1.2 Nausea 18 0 Constipation 16 0 Oral disorder Oral disorder: oral disorder, oral dysesthesia, oral mucosal exfoliation, oral toxicity and oropharyngeal pain. 12 0 Skin and subcutaneous tissue disorders Nail disorder 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. 50 0 Skin disorder Skin disorder: palmar-plantar erythrodysesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation and skin fissures. 41 0.3 Rash 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. 38 3.5 Xerosis Xerosis: dry eye, dry skin and 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 Bacterial infection including sepsis: bacteremia, bacterial prostatitis, carbuncle, cellulitis, citrobacter infection, clostridium difficile colitis, clostridium difficile infection, cystitis escherichia, cystitis klebsiella, diverticulitis, enterobacter bacteremia, escherichia pyelonephritis, escherichia sepsis, folliculitis, gastroenteritis escherichia coli, helicobacter gastritis, human ehrlichiosis, klebsiella bacteremia, klebsiella sepsis, moraxella infection, otitis media acute, pitted keratolysis, pneumococcal sepsis, pneumonia, pneumonia streptococcal, pseudomonal bacteremia, pyuria, renal abscess, salmonella sepsis, sepsis, septic shock, skin infection, staphylococcal bacteremia, staphylococcal infection, staphylococcal sepsis, streptococcal bacteremia, tooth abscess, tooth infection, urinary tract infection enterococcal, and urinary tract infection pseudomonal. Includes fatal outcome(s): COVID-19 (N=2), dyspnea (N=2), bacterial infection including sepsis (N=1), fungal infection (N=1). 19 9 COVID-19 11 2.7 Fungal infection Fungal infection: body tinea, candida infection, ear infection fungal, esophageal candidiasis, fungal infection, fungal sepsis, fungal skin infection, genital candidiasis, onychomycosis, oral candidiasis, oral fungal infection, oropharyngeal candidiasis, tinea pedis, vulvovaginal candidiasis, and vulvovaginal mycotic infection. 10 0.6 Vascular disorders Hypotension 21 2.9 Nervous system disorders Headache 21 0.6 Encephalopathy 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. 15 1.8 Sensory neuropathy Sensory neuropathy: dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, immune-mediated neuropathy, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sciatica and vestibular neuronitis. 14 0 Motor dysfunction Motor dysfunction: dysarthria, dysgraphia, dysmetria, dysphonia, gait disturbance, muscle atrophy, muscle spasms, muscular weakness and tremor. 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. Table 14 summarizes select laboratory abnormalities in MonumenTAL-1. Table 14: Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1 TALVEY The denominator used to calculate the rate varied from 326 to 338 based on the number of patients with a baseline value and at least one post-treatment value. Laboratory Abnormality Any Grade (%) Grade 3 or 4 (%) Laboratory toxicity grades are derived based on the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 4.03. Hematology Lymphocyte count decreased 90 80 White blood cell decreased 73 35 Hemoglobin decreased 67 30 Neutrophil count decreased 64 35 Platelet count decreased 62 22 Chemistry Albumin decreased 66 2.1 Alkaline phosphatase increased 49 1.5 Phosphate decreased 44 13 Gamma-glutamyl transferase increased 38 7 Alanine aminotransferase increased 33 2.7 Potassium decreased 31 4.4 Sodium decreased 31 6 Aspartate aminotransferase increased 31 3.3

<table width="85%" ID="Table13"><caption>Table 13: Adverse Reactions (&#x2265;10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1</caption><col width="60%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th colspan="2" styleCode="Botrule Rrule">TALVEY N=339 </th></tr><tr><th styleCode="Lrule Rrule">System Organ Class Adverse Reaction </th><th styleCode="Rrule">Any Grade (%) </th><th styleCode="Rrule">Grade 3 or 4 (%) </th></tr></thead><tfoot><tr><td colspan="3" align="left" valign="top">Adverse reactions were graded based on CTCAE Version 4.03, with the exception of CRS, which was graded per ASTCT 2019 criteria.</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">General disorders and administration site conditions</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia <footnote ID="ft16">Includes other related terms.</footnote></td><td styleCode="Rrule">83</td><td styleCode="Rrule">4.7 <footnote ID="ft18">Only grade 3 adverse reactions occurred.</footnote></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Fatigue <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">37</td><td styleCode="Rrule">3.5 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Chills</td><td styleCode="Rrule">19</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pain <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">18</td><td styleCode="Rrule">1.8 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Edema <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">14</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Injection site reaction <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">13</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Immune system disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Cytokine release syndrome</td><td styleCode="Rrule">76</td><td styleCode="Rrule">1.5 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Gastrointestinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dysgeusia <footnote ID="K4954">Dysgeusia: ageusia, dysgeusia, hypogeusia and taste disorder. </footnote><footnote ID="ft19">Per CTCAE v4.03, maximum toxicity grade for dysgeusia is 2 and maximum toxicity grade for dry mouth is 3.</footnote></td><td styleCode="Rrule">70</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dry mouth <footnoteRef IDREF="ft19"/></td><td styleCode="Rrule">34</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dysphagia</td><td styleCode="Rrule">23</td><td styleCode="Rrule">0.9 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Diarrhea <footnoteRef IDREF="ft18"/></td><td styleCode="Rrule">21</td><td styleCode="Rrule">0.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Stomatitis <footnote ID="K5009">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.</footnote></td><td styleCode="Rrule">18</td><td styleCode="Rrule">1.2 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">18</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Constipation</td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Oral disorder <footnote ID="K5046">Oral disorder: oral disorder, oral dysesthesia, oral mucosal exfoliation, oral toxicity and oropharyngeal pain.</footnote></td><td styleCode="Rrule">12</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nail disorder <footnote ID="K5070">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.</footnote></td><td styleCode="Rrule">50</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Skin disorder <footnote ID="K5083">Skin disorder: palmar-plantar erythrodysesthesia syndrome, palmoplantar keratoderma, skin discoloration, skin exfoliation and skin fissures.</footnote></td><td styleCode="Rrule">41</td><td styleCode="Rrule">0.3 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rash <footnote ID="K5098">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.</footnote></td><td styleCode="Rrule">38</td><td styleCode="Rrule">3.5 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Xerosis <footnote ID="K5113">Xerosis: dry eye, dry skin and xerosis.</footnote></td><td styleCode="Rrule">30</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pruritus</td><td styleCode="Rrule">19</td><td styleCode="Rrule">0.3 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Musculoskeletal pain <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">43</td><td styleCode="Rrule">3.2 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Investigations</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Weight decreased</td><td styleCode="Rrule">35</td><td styleCode="Rrule">1.5 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Infections and infestations</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Upper respiratory tract infection <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">22</td><td styleCode="Rrule">2.7 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Bacterial infection including sepsis <footnote ID="K5215">Bacterial infection including sepsis: bacteremia, bacterial prostatitis, carbuncle, cellulitis, citrobacter infection, clostridium difficile colitis, clostridium difficile infection, cystitis escherichia, cystitis klebsiella, diverticulitis, enterobacter bacteremia, escherichia pyelonephritis, escherichia sepsis, folliculitis, gastroenteritis escherichia coli, helicobacter gastritis, human ehrlichiosis, klebsiella bacteremia, klebsiella sepsis, moraxella infection, otitis media acute, pitted keratolysis, pneumococcal sepsis, pneumonia, pneumonia streptococcal, pseudomonal bacteremia, pyuria, renal abscess, salmonella sepsis, sepsis, septic shock, skin infection, staphylococcal bacteremia, staphylococcal infection, staphylococcal sepsis, streptococcal bacteremia, tooth abscess, tooth infection, urinary tract infection enterococcal, and urinary tract infection pseudomonal. </footnote><footnote ID="ft17">Includes fatal outcome(s): COVID-19 (N=2), dyspnea (N=2), bacterial infection including sepsis (N=1), fungal infection (N=1).</footnote></td><td styleCode="Rrule">19</td><td styleCode="Rrule">9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> COVID-19 <footnoteRef IDREF="ft16"/><footnoteRef IDREF="ft17"/></td><td styleCode="Rrule">11</td><td styleCode="Rrule">2.7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Fungal infection <footnote ID="K5246">Fungal infection: body tinea, candida infection, ear infection fungal, esophageal candidiasis, fungal infection, fungal sepsis, fungal skin infection, genital candidiasis, onychomycosis, oral candidiasis, oral fungal infection, oropharyngeal candidiasis, tinea pedis, vulvovaginal candidiasis, and vulvovaginal mycotic infection. </footnote><footnoteRef IDREF="ft17"/></td><td styleCode="Rrule">10</td><td styleCode="Rrule">0.6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Vascular disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypotension <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">21</td><td styleCode="Rrule">2.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Nervous system disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Headache <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">21</td><td styleCode="Rrule">0.6 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Encephalopathy <footnote ID="K5311">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.</footnote></td><td styleCode="Rrule">15</td><td styleCode="Rrule">1.8 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Sensory neuropathy <footnote ID="K5326">Sensory neuropathy: dysesthesia, hyperesthesia, hypoesthesia, hypoesthesia oral, immune-mediated neuropathy, neuralgia, neuropathy peripheral, paresthesia, peripheral sensory neuropathy, polyneuropathy, sciatica and vestibular neuronitis.</footnote></td><td styleCode="Rrule">14</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Motor dysfunction <footnote ID="K5339">Motor dysfunction: dysarthria, dysgraphia, dysmetria, dysphonia, gait disturbance, muscle atrophy, muscle spasms, muscular weakness and tremor.</footnote></td><td styleCode="Rrule">10</td><td styleCode="Rrule">0.6 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Metabolism and nutrition disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Decreased appetite</td><td styleCode="Rrule">19</td><td styleCode="Rrule">1.2 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Cough <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">17</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dyspnea <footnoteRef IDREF="ft16"/><footnoteRef IDREF="ft17"/></td><td styleCode="Rrule">11</td><td styleCode="Rrule">1.8</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypoxia <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">10</td><td styleCode="Rrule">1.5 <footnoteRef IDREF="ft18"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Cardiac disorders</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr><td styleCode="Lrule Rrule"> Tachycardia <footnoteRef IDREF="ft16"/></td><td styleCode="Rrule">11</td><td styleCode="Rrule">0.6 <footnoteRef IDREF="ft18"/></td></tr></tbody></table>

<table width="85%" ID="Table14"><caption>Table 14: Select Laboratory Abnormalities (&#x2265;30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received TALVEY in MonumenTAL-1</caption><col width="60%" align="left" valign="top"/><col width="20%" align="center" valign="top"/><col width="20%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule"/><th colspan="2" styleCode="Botrule Rrule">TALVEY <footnote ID="K5481">The denominator used to calculate the rate varied from 326 to 338 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></th></tr><tr><th styleCode="Lrule Rrule" valign="bottom">Laboratory Abnormality</th><th styleCode="Rrule">Any Grade (%) </th><th styleCode="Rrule">Grade 3 or 4 (%) </th></tr></thead><tfoot><tr><td colspan="3" align="left" valign="top">Laboratory toxicity grades are derived based on the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 4.03.</td></tr></tfoot><tbody><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Hematology</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Lymphocyte count decreased</td><td styleCode="Rrule">90</td><td styleCode="Rrule">80</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">White blood cell decreased</td><td styleCode="Rrule">73</td><td styleCode="Rrule">35</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Hemoglobin decreased</td><td styleCode="Rrule">67</td><td styleCode="Rrule">30</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Neutrophil count decreased</td><td styleCode="Rrule">64</td><td styleCode="Rrule">35</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Platelet count decreased</td><td styleCode="Rrule">62</td><td styleCode="Rrule">22</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"><content styleCode="bold">Chemistry</content></td><td styleCode="Rrule"/><td styleCode="Rrule"/></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Albumin decreased</td><td styleCode="Rrule">66</td><td styleCode="Rrule">2.1</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Alkaline phosphatase increased</td><td styleCode="Rrule">49</td><td styleCode="Rrule">1.5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Phosphate decreased</td><td styleCode="Rrule">44</td><td styleCode="Rrule">13</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Gamma-glutamyl transferase increased</td><td styleCode="Rrule">38</td><td styleCode="Rrule">7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Alanine aminotransferase increased</td><td styleCode="Rrule">33</td><td styleCode="Rrule">2.7</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Potassium decreased</td><td styleCode="Rrule">31</td><td styleCode="Rrule">4.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule">Sodium decreased</td><td styleCode="Rrule">31</td><td styleCode="Rrule">6</td></tr><tr><td styleCode="Lrule Rrule">Aspartate aminotransferase increased</td><td styleCode="Rrule">31</td><td styleCode="Rrule">3.3</td></tr></tbody></table>