FDA label d82c287f-a94e-4831-9991-4742cdd17348

WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY, INCLUDING IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves, and modify the next dose or permanently discontinue based on severity [see Dosage and Administration (2.2 , 2.4 , 2.5) and Warnings and Precautions (5.1) ]. Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves, and modify the next dose or permanently discontinue based on severity [see Dosage and Administration (2.2 , 2.4 , 2.5) and Warnings and Precautions (5.2) ]. Because of the risk of CRS and neurologic toxicity, including ICANS, LYNOZYFIC is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the LYNOZYFIC 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 serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Initiate treatment with LYNOZYFIC step-up dosing to reduce the risk of CRS. Manage CRS, withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue based on severity. ( 2.2 , 2.4 , 2.5 , 5.1 ) Neurologic Toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving LYNOZYFIC. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS during treatment. Manage neurologic toxicity, including ICANS, withhold LYNOZYFIC until neurologic toxicity, including ICANS resolves and modify the next dose or permanently discontinue based on severity. ( 2.2 , 2.4 , 2.5 , 5.2 ) LYNOZYFIC is available only through a restricted program called the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS). ( 5.3 )

5 WARNINGS AND PRECAUTIONS Infections : Can cause serious or fatal infections. Monitor patients for signs or symptoms of infection and treat accordingly. ( 5.4 ) Neutropenia : Monitor complete blood cell counts at baseline and periodically during treatment. ( 5.5 ) Hepatotoxicity: Can cause hepatotoxicity. Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. ( 5.6 ) Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Cytokine Release Syndrome (CRS) LYNOZYFIC can cause cytokine release syndrome (CRS), which can be serious or life-threatening. In LINKER-MM1, CRS occurred in 46% (54/117) of patients who received LYNOZYFIC at the recommended dose, with Grade 1 CRS occurring in 35% (41/117) of patients, Grade 2 in 10% (12/117), and Grade 3 in 0.9% (1/117) [see Adverse Reactions (6.1) ] . Thirty-eight percent (45/117) of patients had CRS following step-up dose 1, including 1 patient who experienced Grade 3 CRS; 8% (9/117) had an initial CRS event following a subsequent dose. Seventeen percent (19/113) of patients developed CRS after step-up dose 2, 10% (11/111) developed CRS after the first full 200 mg dose of LYNOZYFIC, and 3.6% (4/110) developed CRS after the second full dose. Recurrent CRS occurred in 20% (23/117) of patients. The median time to onset of CRS from the end of infusion was 11 (range: -1 to 184) hours after the most recent dose with a median duration of 15 (range: 1 to 76) hours. Clinical signs and symptoms of CRS included, but were not limited to pyrexia, chills, hypoxia, tachycardia, and hypotension. Administer pretreatment medications and initiate therapy according to LYNOZYFIC step-up dosing to reduce the incidence and severity of CRS [see Dosage and Administration (2.2) and Dosage and Administration (2.3) ]. Monitor patients for signs and symptoms of CRS after infusion. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care; withhold LYNOZYFIC until CRS resolves and modify the next dose or permanently discontinue LYNOZYFIC based on severity [see Dosage and Administration (2.5) ]. Infusion Related Reactions Infusion-related reactions (IRR) may be clinically indistinguishable from manifestations of CRS. In the patients who were treated with the recommended step-up dosing regimen and pretreatment medications [see Dosage and Administration (2.2) and Dosage and Administration (2.3) ] , the rate of IRR was 9% [11/117 including Grade 2 IRR (4.3%) and Grade 3 IRR (1.7%)]. For IRR, interrupt or slow the rate of infusion or permanently discontinue LYNOZYFIC based on severity of reaction [see Dosage and Administration (2.5) ] . LYNOZYFIC is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.2 Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome LYNOZYFIC can cause serious or life-threatening neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) [see Adverse Reactions (6.1) ]. In LINKER-MM1, neurologic toxicity occurred in 54% of patients, with Grade 3 or 4 neurologic toxicity occurring in 8%, at the recommended dose [see Adverse Reactions (6.1) ]. Neurologic toxicities included ICANS, depressed level of consciousness, encephalopathy, and toxic encephalopathy. ICANS occurred in 8% of patients who received LYNOZYFIC with the recommended dosing regimen, including Grade 3 events in 2.6%. Most patients experienced ICANS following step-up dose 1 (5%). Two patients (1.8%) experienced initial ICANS following step-up dose 2 and one patient developed the first occurrence of ICANS following a subsequent full dose of LYNOZYFIC. Recurrent ICANS occurred in one patient. The median time to onset of ICANS was 1 (range: 1 to 4) day after the most recent dose with a median duration of 2 (range: 1 to 11) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. The most common clinical signs and symptoms of ICANS are confusion, depressed level of consciousness, and lethargy. Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient; provide supportive therapy and consider further management per current practice guidelines. Withhold LYNOZYFIC until ICANS resolves and modify the next dose or permanently discontinue LYNOZYFIC based on severity [see Dosage and Administration (2.5) ] . Counsel patients to seek immediate medical attention should signs or symptoms of neurologic toxicity occur at any time. Due to the potential for neurologic toxicity, including ICANS, patients receiving LYNOZYFIC are at risk of confusion and depressed consciousness. Advise patients to refrain from driving, or operating heavy or potentially dangerous machinery, for 48 hours after completion of each of the step-up doses [see Dosage and Administration (2.2) ] and in the event of new onset of any neurological symptoms, until symptoms resolve. LYNOZYFIC is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.3 LYNOZYFIC REMS LYNOZYFIC is available only through a restricted program under a REMS called the LYNOZYFIC REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 , 5.2) ] . Notable requirements of the LYNOZYFIC REMS include the following: Prescribers must be certified with the program by enrolling and completing training. Prescribers must counsel patients receiving LYNOZYFIC about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with LYNOZYFIC Patient Wallet Card. Pharmacies and healthcare settings that dispense LYNOZYFIC must be certified with the LYNOZYFIC REMS program and must verify prescribers are certified through the LYNOZYFIC REMS program. Wholesalers and distributors must only distribute LYNOZYFIC to certified pharmacies or healthcare settings. Further information about the LYNOZYFIC REMS program is available at lynozyficREMS.com or by telephone at 1-855-212-6391. 5.4 Infections LYNOZYFIC can cause serious, life-threatening, or fatal infections. In patients who received LYNOZYFIC at the recommended dose in LINKER-MM1, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade 3 or 4 infections in 38% and fatal infections in 4% [see Adverse Reactions (6.1) ] . The most common serious infection reported (≥10%) were pneumonia and sepsis. Two cases of progressive multifocal leukoencephalopathy (PML) occurred in patients receiving LYNOZYFIC. Monitor patients for signs and symptoms of infection and immunoglobulin levels prior to and during treatment with LYNOZYFIC and treat appropriately. Administer prophylactic antimicrobials, antibiotics, antifungals, antivirals, vaccines, and subcutaneous or intravenous immunoglobulin (IVIG) according to guidelines, including prophylaxis for PJP and herpesviruses [see Dosage and Administration (2.3) ] . Withhold LYNOZYFIC or consider permanent discontinuation of LYNOZYFIC based on severity of the infection [see Dosage and Administration (2.5) ] . 5.5 Neutropenia LYNOZYFIC can cause neutropenia and febrile neutropenia. In patients who received LYNOZYFIC at the recommended dose in LINKER-MM1, decreased neutrophil count occurred in 62% of patients with Grade 3 or 4 decreased neutrophil count in 47%. Febrile neutropenia occurred in 8% of patients [see Adverse Reactions (6.1) ] . Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local guidelines. Monitor patients with neutropenia for signs of infection. Withhold LYNOZYFIC based on severity [see Dosage and Administration (2.5) ] . 5.6 Hepatotoxicity LYNOZYFIC can cause hepatotoxicity. In LINKER-MM1, elevated ALT occurred in 46% of patients, with Grade 3 or 4 ALT elevation occurring in 6%; elevated AST occurred in 61% of patients, with Grade 3 or 4 AST elevation occurring in 10% of patients who received the recommended dose. Grade 3 or 4 total bilirubin elevations occurred in 1.7% 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 LYNOZYFIC or consider permanent discontinuation of LYNOZYFIC based on severity [see Dosage and Administration (2.5) ]. 5.7 Embryo-Fetal Toxicity Based on its mechanism of action, LYNOZYFIC 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 LYNOZYFIC and for 3 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] Neurologic Toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome [see Warnings and Precautions (5.2) ] Infections [see Warnings and Precautions (5.4) ] Neutropenia [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥20%) are musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea. ( 6.1 ) The most common Grade 3 or 4 laboratory abnormalities (≥30%) are decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Regeneron at 1-844-467-2998 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 or Refractory Multiple Myeloma The safety of LYNOZYFIC was evaluated in LINKER-MM1 [see Clinical Studies (14) ] . Patients (n=117) received LYNOZYFIC as step-up doses of 5 mg on Day 1 and 25 mg on Day 8, and the first treatment dose of 200 mg on Day 15. Patients then received 200 mg intravenously once weekly from Week 4 to Week 13, followed by 200 mg every 2 weeks from Week 14. In the Phase 2 portion of the study, patients who achieved and maintained VGPR or better at or after Week 24 and received at least 17 doses of 200 mg were able to receive every 4-week dosing. The median duration of treatment was 47 weeks (range 1, 151); 55% of patients were exposed for 9 months or longer and 36% were exposed for 1 year or longer. The median age of patients who received LYNOZYFIC was 70 years (range: 37 to 91 years); 55% were male; 71% were White, 17% were Black or African American, and 9% were Asian. Serious adverse reactions occurred in 74% of patients who received LYNOZYFIC. Serious adverse reactions that occurred in >5% of patients included cytokine release syndrome (27%), pneumonia (13%), COVID-19 (7%), and acute kidney injury (5%). Fatal adverse reactions occurred in 7% of patients, and included sepsis (3.4%), chronic kidney disease (0.9%), pneumonia (0.9%), tumor lysis syndrome (0.9%), and encephalopathy (0.9%). Permanent discontinuation of LYNOZYFIC due to adverse reactions occurred in 16% of patients. Adverse reactions leading to discontinuation that occurred in at least 2 patients included sepsis, pneumonia, and encephalopathy. Dosage interruptions or delays of LYNOZYFIC due to adverse reactions occurred in 74% of patients. Adverse reactions which required a dosage interruption or delay in >10% of patients included neutropenia (29%), upper respiratory tract infection (18%), pneumonia (15%), and COVID-19 infection (11%). The most common adverse reactions (≥20%) were musculoskeletal pain, cytokine release syndrome, cough, upper respiratory tract infection, diarrhea, fatigue, pneumonia, nausea, headache, and dyspnea. The most common Grade 3 to 4 laboratory abnormalities (≥30%) were decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count. Table 7 summarizes the adverse reactions in LINKER-MM1. Table 7: Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received LYNOZYFIC in LINKER-MM1 Adverse Reaction LYNOZYFIC (N=117) All Grades (%) Grade 3 or 4 (%) Musculoskeletal and connective tissue disorders Musculoskeletal pain Includes other related terms. 53 3.4 Only Grade 3 adverse reactions occurred. Immune system disorders Cytokine release syndrome 46 0.9 Hypogammaglobulinemia 13 0.9 Respiratory, thoracic and mediastinal disorders Cough 39 0 Dyspnea 21 0.9 Nasal congestion 16 0 Infections and infestations Upper respiratory tract infection 35 6 Pneumonia Pneumonia includes atypical pneumonia, COVID-19 pneumonia, PJP, pneumonia, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, and pneumonia viral. , Includes fatal outcome. 28 21 COVID-19 17 5 Urinary tract infections 16 8 Sepsis 10 6 Gastrointestinal disorders Diarrhea 35 1.7 Nausea 23 0 Vomiting 19 0 Constipation 17 0 General disorders and administration site conditions Fatigue 34 0 Edema 19 0.9 Pyrexia 17 0 Nervous system disorders Headache 22 0.9 Encephalopathy , Encephalopathy includes agitation, amnesia, cognitive disorder, confusional state, delirium, depressed level of consciousness, encephalopathy (including hyperammonemic and toxic encephalopathy), irritability, lethargy, memory impairment, mental status changes, somnolence, and excludes ICANS. 18 3.4 Sensory Neuropathy 13 0.9 Metabolism and nutrition disorders Decreased appetite 15 0.9 Skin and subcutaneous tissue disorders Rash Rash includes dermatitis acneiform, dermatitis contact, drug eruption, erythema, rash, rash erythematous, rash maculo-papular, rash pruritic, and stasis dermatitis. 15 1.7 Psychiatric disorders Insomnia 13 0 Vascular disorders Hypertension 10 4.3 Clinically significant adverse reactions that occurred in <10% of patients treated with LYNOZYFIC included IRR, motor dysfunction, febrile neutropenia, ICANS, CMV infection, and PML. Table 8 summarizes the laboratory abnormalities in LINKER-MM1. Table 8: Select Laboratory Abnormalities (≥5% for Grade 3 or 4) That Worsened from Baseline in Patients with Multiple Myeloma Treated with LYNOZYFIC in LINKER-MM1 Laboratory Abnormality Laboratory tests were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 5.0. LYNOZYFIC (N=117) The denominator used to calculate the rate varied from 106 to 117 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grades 3 or 4 (%) Hematology Lymphocyte count decreased 97 92 Hemoglobin decreased 72 42 Platelet count decreased 64 19 White blood cell count decreased 63 31 Neutrophil count decreased 62 47 Chemistry Aspartate aminotransferase increased 61 10 Phosphorus decreased 55 24 Creatinine increased 47 7 Alanine aminotransferase increased 46 6

<table width="75%"><caption>Table 7: Adverse Reactions (&#x2265;10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received LYNOZYFIC in LINKER-MM1</caption><col width="50%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr styleCode="Botrule"><th styleCode="Lrule Rrule" rowspan="2">Adverse Reaction</th><th styleCode="Rrule" colspan="2">LYNOZYFIC (N=117)</th></tr><tr><th styleCode="Rrule" align="center">All Grades (%)</th><th styleCode="Rrule">Grade 3 or 4 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Musculoskeletal pain<footnote ID="Tb7ft2">Includes other related terms.</footnote></td><td styleCode="Rrule">53</td><td styleCode="Rrule">3.4<footnote ID="Tb7ft">Only Grade 3 adverse reactions occurred.</footnote></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Immune system disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Cytokine release syndrome</td><td styleCode="Rrule">46</td><td styleCode="Rrule">0.9<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hypogammaglobulinemia</td><td styleCode="Rrule">13</td><td styleCode="Rrule">0.9<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Cough<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">39</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Dyspnea<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">21</td><td styleCode="Rrule">0.9<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nasal congestion</td><td styleCode="Rrule">16</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Infections and infestations</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Upper respiratory tract infection<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">35</td><td styleCode="Rrule">6<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pneumonia<footnote>Pneumonia includes atypical pneumonia, COVID-19 pneumonia, PJP, pneumonia, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, and pneumonia viral.</footnote>^,<footnote ID="Tb7ft3">Includes fatal outcome.</footnote></td><td styleCode="Rrule">28</td><td styleCode="Rrule">21</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> COVID-19</td><td styleCode="Rrule">17</td><td styleCode="Rrule">5</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Urinary tract infections<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">16</td><td styleCode="Rrule">8<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Sepsis</td><td styleCode="Rrule">10</td><td styleCode="Rrule">6</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Gastrointestinal disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Diarrhea</td><td styleCode="Rrule">35</td><td styleCode="Rrule">1.7<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Nausea</td><td styleCode="Rrule">23</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Vomiting</td><td styleCode="Rrule">19</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Constipation</td><td styleCode="Rrule">17</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">General disorders and administration site conditions</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Fatigue<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">34</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Edema<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">19</td><td styleCode="Rrule">0.9<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Pyrexia</td><td styleCode="Rrule">17</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Nervous system disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Headache<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">22</td><td styleCode="Rrule">0.9<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Encephalopathy<footnoteRef IDREF="Tb7ft3"/>^,<footnote>Encephalopathy includes agitation, amnesia, cognitive disorder, confusional state, delirium, depressed level of consciousness, encephalopathy (including hyperammonemic and toxic encephalopathy), irritability, lethargy, memory impairment, mental status changes, somnolence, and excludes ICANS.</footnote></td><td styleCode="Rrule">18</td><td styleCode="Rrule">3.4</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Sensory Neuropathy<footnoteRef IDREF="Tb7ft2"/></td><td styleCode="Rrule">13</td><td styleCode="Rrule">0.9</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Metabolism and nutrition disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Decreased appetite</td><td styleCode="Rrule">15</td><td styleCode="Rrule">0.9<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Skin and subcutaneous tissue disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Rash<footnote>Rash includes dermatitis acneiform, dermatitis contact, drug eruption, erythema, rash, rash erythematous, rash maculo-papular, rash pruritic, and stasis dermatitis.</footnote></td><td styleCode="Rrule">15</td><td styleCode="Rrule">1.7<footnoteRef IDREF="Tb7ft"/></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Psychiatric disorders</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Insomnia</td><td styleCode="Rrule">13</td><td styleCode="Rrule">0</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule" colspan="3"><content styleCode="bold">Vascular disorders</content></td></tr><tr><td styleCode="Lrule Rrule"> Hypertension</td><td styleCode="Rrule">10</td><td styleCode="Rrule">4.3<footnoteRef IDREF="Tb7ft"/></td></tr></tbody></table>

<table width="85%"><caption>Table 8: Select Laboratory Abnormalities (&#x2265;5% for Grade 3 or 4) That Worsened from Baseline in Patients with Multiple Myeloma Treated with LYNOZYFIC in LINKER-MM1</caption><col width="50%" align="left" valign="top"/><col width="25%" align="center" valign="top"/><col width="25%" align="center" valign="top"/><thead><tr><th styleCode="Lrule Rrule">Laboratory Abnormality<footnote styleCode="foot7">Laboratory tests were graded according to NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Version 5.0.</footnote></th><th styleCode="Botrule Rrule" colspan="2">LYNOZYFIC (N=117)<footnote>The denominator used to calculate the rate varied from 106 to 117 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"/><th styleCode="Rrule">All Grades (%)</th><th styleCode="Rrule">Grades 3 or 4 (%)</th></tr></thead><tbody><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Hematology</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Lymphocyte count decreased</td><td styleCode="Rrule">97</td><td styleCode="Rrule">92</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Hemoglobin decreased</td><td styleCode="Rrule">72</td><td styleCode="Rrule">42</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Platelet count decreased</td><td styleCode="Rrule">64</td><td styleCode="Rrule">19</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> White blood cell count decreased</td><td styleCode="Rrule">63</td><td styleCode="Rrule">31</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Neutrophil count decreased</td><td styleCode="Rrule">62</td><td styleCode="Rrule">47</td></tr><tr styleCode="Botrule"><td colspan="3" styleCode="Lrule Rrule"><content styleCode="bold">Chemistry</content></td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Aspartate aminotransferase increased</td><td styleCode="Rrule">61</td><td styleCode="Rrule">10</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Phosphorus decreased</td><td styleCode="Rrule">55</td><td styleCode="Rrule">24</td></tr><tr styleCode="Botrule"><td styleCode="Lrule Rrule"> Creatinine increased</td><td styleCode="Rrule">47</td><td styleCode="Rrule">7</td></tr><tr><td styleCode="Lrule Rrule"> Alanine aminotransferase increased</td><td styleCode="Rrule">46</td><td styleCode="Rrule">6</td></tr></tbody></table>