Elrexfio

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 ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce the risk of CRS. Withhold ELREXFIO 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 reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue 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, ELREXFIO is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ELREXFIO 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 ELREXFIO. Initiate treatment with ELREXFIO step-up dosing schedule to reduce risk of CRS. Withhold ELREXFIO 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 reactions, can occur in patients receiving ELREXFIO. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment. Withhold ELREXFIO until the neurologic toxicity resolves or permanently discontinue based on severity. ( 2.5 , 5.2 ) • ELREXFIO is available only through a restricted program called the ELREXFIO Risk Evaluation and Mitigation Strategy (REMS). ( 5.3 )

5 WARNINGS AND PRECAUTIONS • Infections : Can cause severe, life-threatening, or fatal infections. Monitor patients for signs and symptoms of infection and treat appropriately. Do not initiate treatment in patients with active infections. ( 5.4 ) • Neutropenia : Monitor complete blood cell counts at baseline and periodically during treatment. ( 5.5 ) • Hepatotoxicity : Can cause elevated ALT, AST, and bilirubin. 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) ELREXFIO can cause CRS, including life-threatening or fatal reactions [see Adverse Reactions (6.1) ] . In the clinical trial, CRS occurred in 58% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2) ] , with Grade 1 CRS in 44% of patients, Grade 2 CRS in 14% of patients, and Grade 3 CRS in 0.5% of patients. Recurrent CRS occurred in 13% of patients. Most patients experienced CRS after the first step-up dose (43%) or the second step-up dose (19%), with 7% of patients having CRS after the first treatment dose and 1.6% of patients after a subsequent dose. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose, with a median duration of 2 (range: 1 to 19) days. Clinical signs and symptoms of CRS may include, but are not limited to, fever, hypoxia, chills, hypotension, tachycardia, headache, and elevated liver enzymes. Initiate therapy according to the ELREXFIO step-up dosing schedule to reduce risk of CRS and monitor patients following administration of ELREXFIO accordingly [see Dosage and Administration (2.2 , 2.5 )] . Administer pre-treatment medications prior to each dose in the step-up dosing schedule to reduce risk of CRS [see Dosage and Administration (2.3) ] . Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, evaluate patients immediately for hospitalization. Manage CRS according to the recommendations and consider further management per current practice guidelines. Withhold or permanently discontinue ELREXFIO based on severity [see Dosage and Administration (2.5) ] . ELREXFIO 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 (ICANS) ELREXFIO can cause serious or life-threatening neurologic toxicity, including ICANS [see Adverse Reactions (6.1) ] . In the clinical trial, neurologic toxicity occurred in 59% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2) ] , with Grade 3 or 4 neurologic toxicity occurring in 7% of patients. Neurologic toxicities included headache (18%), encephalopathy (15%), motor dysfunction (13%), sensory neuropathy (13%), and Guillain-Barré Syndrome (0.5%). In the clinical trial, ICANS occurred in 3.3% of patients who received ELREXFIO at the recommended dosing schedule [see Dosage and Administration (2.2) ] . Most patients had ICANS after the first step-up dose (2.7%), 1 (0.5%) patient had ICANS after the second step-up dose and 1 (0.5%) patient had ICANS after subsequent dose(s). Recurrent ICANS occurred in 1.1% of patients. The median time to onset was 3 (range: 1 to 4) days after the most recent dose, with a median duration of 2 (range: 1 to 18) days. The most frequent clinical manifestations of ICANS included a depressed level of consciousness and Grade 1 or Grade 2 Immune Effector Cell-Associated Encephalopathy (ICE) scores. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity occur. Monitor patients for signs and symptoms of neurologic toxicities during treatment with ELREXFIO. At the first sign of neurologic toxicity, including ICANS, evaluate and treat patients immediately based on severity. Withhold or permanently discontinue ELREXFIO based on severity per recommendations [see Dosage and Administration (2.5) ] and consider further management per current practice guidelines. Due to the potential for neurologic toxicity including ICANS, patients receiving ELREXFIO are at risk of depressed level of consciousness. Advise patients not to drive or operate heavy or potentially dangerous machinery for 48 hours after completing each of the 2 step-up doses and the first treatment dose within the ELREXFIO step-up dosing schedule and in the event of new onset of any neurological toxicity symptoms until symptoms resolve [see Dosage and Administration (2.2) ] . ELREXFIO is available only through a restricted program under a REMS [see Warnings and Precautions (5.3) ] . 5.3 ELREXFIO REMS ELREXFIO is available only through a restricted program under a REMS called the ELREXFIO REMS because of the risks of CRS and neurologic toxicity, including ICANS [see Warnings and Precautions (5.1 , 5.2 )] . Notable requirements of the ELREXFIO REMS include the following: • Prescribers must be certified with the program by enrolling and completing training. • Prescribers must counsel patients receiving ELREXFIO about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with ELREXFIO Patient Wallet Card. • Pharmacies and healthcare settings that dispense ELREXFIO must be certified with the ELREXFIO REMS program and must verify prescribers are certified through the ELREXFIO REMS program. • Wholesalers and distributers must only distribute ELREXFIO to certified pharmacies or healthcare settings. Further information about the ELREXFIO REMS program is available at www.ELREXFIOREMS.com or by telephone at 1‑844‑923‑7845. 5.4 Infections ELREXFIO can cause severe, life-threatening, or fatal infections. In the clinical trial, in patients who received ELREXFIO according to the recommended dosing schedule, serious infections, including opportunistic infections, occurred in 42% of patients, with Grade 3 or 4 infections in 31%, and fatal infections in 7%. The most common serious infections reported (≥5%) were pneumonia and sepsis [see Adverse Reactions (6.1) ] . Do not initiate treatment with ELREXFIO in patients with active infections. Monitor patients for signs and symptoms of infection prior to and during treatment with ELREXFIO and treat appropriately. Withhold or permanently discontinue ELREXFIO based on severity [see Dosage and Administration (2.5) ] . Administer prophylactic antimicrobial and anti-viral medications according to current practice guidelines. Consider treatment with subcutaneous or intravenous immunoglobulin (IVIG) as appropriate. 5.5 Neutropenia ELREXFIO can cause neutropenia and febrile neutropenia. In patients who received ELREXFIO at the recommended dose in the clinical trial, decreased neutrophils occurred in 62% of patients, with Grade 3 or 4 decreased neutrophils in 51%. Febrile neutropenia occurred in 2.2% of patients [see Adverse Reactions (6.1) ] . Monitor complete blood cell counts at baseline and periodically during treatment. Provide supportive care according to current practice guidelines. Monitor patients with neutropenia for signs of infection. Withhold ELREXFIO based on severity [see Dosage and Administration (2.5) ] . 5.6 Hepatotoxicity ELREXFIO can cause hepatotoxicity. In the clinical trial, elevated ALT occurred in 36% of patients, with Grade 3 or 4 ALT elevation occurring in 3.8%; elevated AST occurred in 40% of patients, with Grade 3 or 4 AST elevation occurring in 6%. Grade 3 or 4 total bilirubin elevations occurred in 0.5% 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 ELREXFIO or consider permanent discontinuation of ELREXFIO based on severity [see Dosage and Administration (2.5) ] . 5.7 Embryo-Fetal Toxicity Based on its mechanism of action, ELREXFIO 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 ELREXFIO and for 4 months after the last dose [see Use in Specific Populations (8.1 , 8.3 )] .

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in labeling: • Cytokine Release Syndrome [see Warnings and Precautions (5.1) ] . • Neurologic Toxicity, Including ICANS [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) ] . Most common adverse reactions (incidence ≥20%) are CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) are decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 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 MagnetisMM-3 The safety of ELREXFIO was evaluated in MagnetisMM-3 [see Clinical Studies (14) ]. The safety population described (n = 183) includes patients who received the recommended dosage regimen of 12 mg subcutaneously on Day 1, 32 mg on Day 4, and 76 mg once weekly starting on Day 8. Among patients who received ELREXFIO, 42% were exposed for 6 months or longer and 9% were exposed for one year or longer. The median age of patients who received ELREXFIO was 68 years (range: 36 to 88 years); 48% were female; 61% were White, 10% were Hispanic/Latino, 9% were Asian, and 6% were Black or African American. Serious adverse reactions occurred in 68% of patients who received ELREXFIO at the recommended dosing schedule. Serious adverse reactions in >2% of patients included pneumonia (25%), sepsis (13%), CRS (13%), upper respiratory tract infection (4.4%), acute kidney injury (3.8%), urinary tract infection (3.3%), COVID-19 (3.3%), encephalopathy (3.3%), pyrexia (2.2%), and febrile neutropenia (2.2%). Fatal adverse reactions occurred in 10% of patients including pneumonia (3.3%), sepsis (2.7%), acute respiratory distress syndrome (0.5%), cardio-respiratory arrest (0.5%), cardiogenic shock (0.5%), cardiopulmonary failure (0.5%), COVID-19 (0.5%), failure to thrive (0.5%), and pulmonary embolism (0.5%). Permanent discontinuations of ELREXFIO due to an adverse reaction occurred in 17% of patients. Adverse reactions which resulted in permanent discontinuation of ELREXFIO in >2% of patients included septic shock (2.2%). Dosage interruptions of ELREXFIO due to an adverse reaction occurred in 73% of patients. Adverse reactions which resulted in dose interruptions of ELREXFIO in >5% of patients included neutropenia, pneumonia, COVID-19, upper respiratory tract infection, thrombocytopenia, and anemia. The most common adverse reactions (≥20%) were CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common Grade 3 to 4 laboratory abnormalities (≥30%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets. Table 8 summarizes adverse reactions in MagnetisMM-3. Table 8. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3 Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria. System Organ Class Preferred Term ELREXFIO N = 183 All Grades (%) Grade 3 or 4 (%) Immune system disorders Cytokine release syndrome 58 0.5 Only grade 3 adverse reactions occurred. Hypogammaglobulinemia Includes other related terms. 13 2.2 General disorders and site administration conditions Fatigue 43 6 Injection site reaction 37 0 Pyrexia 21 2.7 Edema 18 1.1 Gastrointestinal disorders Diarrhea 36 1.1 Nausea 21 0 Constipation 14 0 Vomiting 14 0 Infections Upper respiratory tract infection 36 4.9 Pneumonia Pneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral. 32 19 Sepsis Sepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis. 15 11 Urinary tract infection 12 4.4 Musculoskeletal and connective tissue disorders Musculoskeletal pain 34 2.7 Metabolism and nutrition disorders Decreased appetite 26 1.1 Skin and Subcutaneous Tissue disorders Rash Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema. 26 0 Dry skin 14 0 Skin exfoliation 10 0 Respiratory, thoracic and mediastinal disorders Cough 24 0 Dyspnea 15 3.3 Nervous system disorders Headache 18 0 Encephalopathy Encephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy. 14 2.2 Sensory neuropathy Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss. 13 0.5 Motor dysfunction Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor. 14 1.1 Cardiac disorders Cardiac arrhythmia 16 1.6 Vascular disorders Hemorrhage 13 1.6 Psychiatric disorders Insomnia 13 0 Injury, poisoning and procedural complications Fall 10 0.5 Clinically relevant adverse reactions in <10% of patients who received ELREXFIO included ICANS, febrile neutropenia, Guillain-Barré syndrome, abdominal pain, acute kidney injury, COVID-19, cardiac failure, congestion, thrombosis, cytomegalovirus infection, and progressive multifocal leukoencephalopathy. Table 9 summarizes laboratory abnormalities in MagnetisMM-3. Table 9. Select Laboratory Abnormalities (≥30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3 Laboratory tests were graded according to NCI-CTCAE Version 5.0. Laboratory Abnormality ELREXFIO The denominator used to calculate the rate varied from 181 to 183 based on the number of patients with a baseline value and at least one post-treatment value. All Grades (%) Grade 3 or 4 (%) Hematology Lymphocyte count decreased 91 84 White blood cell decreased 69 40 Hemoglobin decreased 68 43 Neutrophil count decreased 62 51 Platelet count decreased 61 32 Chemistry Albumin decreased 55 6 AST increase 40 6 Creatinine increased 38 3.3 Potassium decreased 36 8 ALT increase 36 3.8 Alkaline phosphatase increased 34 1.1 Creatinine clearance decreased 32 10

<table styleCode="Noautorules" width="100%"><caption>Table 8. Adverse Reactions (&#x2265;10%) in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3</caption><col width="50%"/><col width="25%"/><col width="25%"/><tfoot><tr><td align="left" colspan="3" valign="top">Adverse reactions were graded based on CTCAE Version 5.0, with the exception of CRS, which was graded based on the ASTCT 2019 criteria.</td></tr></tfoot><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">System Organ Class</content></paragraph><paragraph><content styleCode="bold">Preferred Term</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph><content styleCode="bold">ELREXFIO</content></paragraph><paragraph><content styleCode="bold">N = 183</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"/><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3 or 4</content></paragraph><paragraph><content styleCode="bold">(%)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Immune system disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Cytokine release syndrome</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>58</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5<footnote ID="_Ref139283107">Only grade 3 adverse reactions occurred.</footnote></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hypogammaglobulinemia<footnote ID="_Ref139284176">Includes other related terms.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.2<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">General disorders and site administration conditions</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Fatigue<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>43</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Injection site reaction<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>37</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pyrexia</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.7<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Edema<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.1<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Gastrointestinal disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Diarrhea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.1<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Nausea</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>21</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Constipation</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Vomiting</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Infections</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Upper respiratory tract infection<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4.9</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Pneumonia<footnote ID="_Ref139284560">Pneumonia includes COVID-19 pneumonia, lower respiratory tract infection, lower respiratory tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia adenoviral, pneumonia bacterial, pneumonia cytomegaloviral, pneumonia fungal, pneumonia influenzal, pneumonia pseudomonal, pneumonia viral.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>19</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sepsis<footnote ID="_Ref139284565">Sepsis includes bacteremia, device related bacteremia, device related sepsis, escherichia bacteremia, escherichia sepsis, klebsiella sepsis, pseudomonal sepsis, sepsis, septic shock, staphylococcal bacteremia, staphylococcal sepsis, streptococcal sepsis, urosepsis.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>11</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Urinary tract infection<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>12</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>4.4<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Musculoskeletal pain<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>34</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.7<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.1<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Skin and Subcutaneous Tissue disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Rash<footnote ID="_Ref139284747">Rash incudes erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash pustular, symmetrical drug-related intertriginous and flexural exanthema.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>26</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dry skin</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Skin exfoliation<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Cough<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>24</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Dyspnea<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>15</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Nervous system disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Headache</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>18</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Encephalopathy<footnote ID="_Ref139284809">Encephalopathy includes agitation, altered state of consciousness, cognitive disorder, confusional state, delirium, depressed level of consciousness, disorientation, hallucination, lethargy, memory impairment, metabolic encephalopathy, somnolence, toxic encephalopathy.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>2.2</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Sensory neuropathy<footnote ID="_Ref139284814">Sensory neuropathy includes burning sensation, dysesthesia, hypoesthesia, neuropathy peripheral, paresthesia, parosmia, peripheral sensorimotor neuropathy, peripheral sensory neuropathy, polyneuropathy, sensory loss.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0.5<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Motor dysfunction<footnote ID="_Ref139284839">Motor dysfunction includes ataxia, balance disorder, gait disturbance, motor dysfunction, muscle contracture, muscle spasms, muscular weakness, peripheral motor neuropathy, peroneal nerve palsy, tremor.</footnote></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>14</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.1<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Cardiac disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Cardiac arrhythmia<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>16</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Vascular disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hemorrhage<footnoteRef IDREF="_Ref139284176"/></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Psychiatric disorders</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Insomnia </paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>13</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>0</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Injury, poisoning and procedural complications</content></paragraph></td><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/><td styleCode="Rrule Lrule Toprule Botrule " valign="top"/></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Fall</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>10</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>0.5<footnoteRef IDREF="_Ref139283107"/></paragraph></td></tr></tbody></table>

<table styleCode="Noautorules" width="100%"><caption>Table 9. Select Laboratory Abnormalities (&#x2265;30%) That Worsened from Baseline in Patients with Relapsed or Refractory Multiple Myeloma Who Received ELREXFIO in MagnetisMM-3<footnote ID="_Ref121147321">Laboratory tests were graded according to NCI-CTCAE Version 5.0.</footnote></caption><col width="33%"/><col width="33%"/><col width="33%"/><tbody><tr><td rowspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">Laboratory Abnormality</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Lrule Toprule " valign="middle"><paragraph><content styleCode="bold">ELREXFIO</content><footnote ID="_Ref139285016">The denominator used to calculate the rate varied from 181 to 183 based on the number of patients with a baseline value and at least one post-treatment value.</footnote></paragraph></td></tr><tr><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">All Grades (%)</content></paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph><content styleCode="bold">Grade 3 or 4 (%)</content></paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Hematology</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Lymphocyte count decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>91</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>84</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>White blood cell decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>69</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>40</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Hemoglobin decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>68</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>43</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Neutrophil count decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>62</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>51</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Platelet count decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>61</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>32</paragraph></td></tr><tr><td colspan="3" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold">Chemistry</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Albumin decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>55</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>AST increase</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>40</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>6</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Creatinine increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>38</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.3</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Potassium decreased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>ALT increase</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>36</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>3.8</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Alkaline phosphatase increased</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>34</paragraph></td><td align="center" styleCode="Rrule Lrule Toprule Botrule " valign="top"><paragraph>1.1</paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>Creatinine clearance decreased</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>32</paragraph></td><td align="center" styleCode="Rrule Botrule Lrule Toprule " valign="top"><paragraph>10</paragraph></td></tr></tbody></table>