b'B:8.5"T:7.5"S:7"Serious adverse reactions occurred in 59% of patients receiving Isa-Kd. The most frequent SARCLISA seriousadversereactionsin 5%ofpatientswhoreceivedIsa-Kdwerepneumonia(25%)and (isatuximab-irfc) injection, for intravenous useupperrespiratorytractinfections(9%).Adversereactionswithafataloutcomeduringtreatment Table 6: Hematology Laboratory Abnormalities During the Treatment Period inwere reported in 3.4% of patients in the Isa-Kd group (those occurring in more than 1% of Patients Receiving Isa-Kd versus Kd in IKEMApatients were pneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).Permanent treatment discontinuation due to an adverse reaction (grades 14) occurred in 8% Laboratory SARCLISA + Carlzomib + Carlzomib +of patients who received Isa-Kd. The most frequent adverse reactions requiring permanent Parameter Dexamethasone (Isa-Kd) Dexamethasone (Kd)discontinuation in patients who received Isa-Kd were infections (2.8%). SARCLISAalone was (N=177) (N=122)discontinued in 0.6% of patients due to infusion-related reactions.Dosage interruptions due to an adverse reaction occurred in 33% of patients who received All Grade 3 Grade 4 All Grade 3 Grade 4SARCLISA. The most frequent adverse reaction requiring dosage interruption was infusion- Grades (%) (%) Grades (%) (%)related reaction (30%). (%) (%)The most common adverse reactions (20%) were upper respiratory tract infection, infusion- Hemoglobin 99 22 0 99 20 0related reactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea, insomnia, bronchitis, decreasedcough, and back pain. Lymphocytes 94 52 17 95 43 14Table 5 summarizes the adverse reactions in IKEMA. decreasedTable 5: Adverse Reactions (10%) in Patients Receiving SARCLISA, Carlzomib, Platelets decreased 94 19 11 88 16 8and Dexamethasone with a Difference Between Arms of 5% Compared to Control Neutrophils 55 18 1.7 43 7 0.8Arm in IKEMA decreasedAdverse SARCLISA + Carlzomib + Carlzomib + Dexamethasone The denominator used to calculate the percentage was based on the safety population.Reactions Dexamethasone (Isa-Kd) (Kd)(N=177) (N=122) Description of Selected Adverse ReactionsInfusion-related reactionsAll Grade Grade All Grade Grade In ICARIA-MM, infusion-related reactions (dened as adverse reactions associated with theGrades 3 4 Grades 3 4 SARCLISAinfusions,withanonsettypicallywithin24hoursfromthestartoftheinfusion)were(%) (%) (%) (%) (%) (%) reported in 58 patients (38%) treated with SARCLISA.All patients who experienced infusion-General disorders and administration site conditions related reactions experienced them during the 1st infusion of SARCLISA, with 3 patients (2%)also having infusion-related reactions at their 2nd infusion, and 2 patients (1.3%) at their 4thInfusion-related 46 0.6 0 3.3 0 0 infusion.Grade1infusion-relatedreactionswerereportedin3.9%,grade2in32%,grade3inreaction * 1.3%,andgrade4in1.3%ofthepatients.Signsandsymptomsofgrade3or4infusion-related reactions included dyspnea, hypertension, and bronchospasm. The incidence of infusionFatigue 42 5 0 32 3.3 0 interruptions because of infusion-related reactions was 30%. The median time to infusionInfections interruption was 55 minutes. SARCLISA was discontinued in 2.6% of patients due toinfusion-related reactions.Upper respiratory 67 9 0 57 7 0 In IKEMA, infusion-related reactions were reported in 81 patients (46%) treated with Isa-Kd.tract infectionGrade1infusion-relatedreactionswerereportedin14%,grade2in32%,andgrade3in0.6%Pneumonia36 19 3.4 30 15 2.5 of the patients treated with Isa-Kd. Signs and symptoms of grade 3 infusion-related reactionsincluded dyspnea and hypertension. SARCLISA was discontinued in 0.6% of patients due to S:10" T:10.5" B:11.25"Bronchitis24 2.3 0 13 0.8 0 infusion-related reactions [see Warnings and Precautions (5.1)].Inaseparatestudy(TCD14079PartB)withSARCLISA10mg/kgadministeredfroma250mLVascular disorders xed-volume infusion in combination with Pd, infusion-related reactions (all grade 2) wereHypertension # 37 20 0.6 32 18 1.6 reported in 40% of patients, at the rst administration, the day of the infusion. Overall, theinfusion-related reactions of SARCLISA 10 mg/kg administered as a 250 mL xed-volumeRespiratory, thoracic and mediastinal disorders infusion were similar to that of SARCLISA as administered in ICARIA-MM.InfectionsDyspnea29 5 0 24 0.8 0 In ICARIA-MM, the incidence of grade 3 or higher infections was 43% in the Isa-Pd group.Cough23 0 0 15 0 0 Pneumonia was the most common severe infection with grade 3 reported in 22% of patientsin the Isa-Pd group compared to 16% in the Pd group, and grade 4 in 3.3% of patients in theGastrointestinal disorders Isa-Pd group compared to 2.7% in the Pd group. Discontinuations from treatment due toinfectionwerereportedin2.6%ofpatientsintheIsa-Pdgroupcomparedto5%inthePdgroup.Diarrhea 36 2.8 0 29 2.5 0 Fatal infections occurred in 3.3% of patients in the Isa-Pd group and in 4% in the Pd group.Vomiting 15 1.1 0 9 0.8 0 InIKEMA,theincidenceofgrade3orhigherinfectionswas38%intheIsa-Kdgroup.Pneumoniawas the most common severe infection with grade 3 in 19% of patients in the Isa-Kd group*Infusion-related reaction includes infusion-related reaction, cytokine release syndrome, and comparedto15%intheKdgroup,andgrade4in3.4%ofpatientsintheIsa-Kdgroupcomparedhypersensitivity. to2.5%intheKdgroup.Treatmentwasdiscontinuedduetoinfectionin2.8%ofpatientsintheFatigue includes fatigue and asthenia. Isa-Kd group compared to 4.9% in the Kd group. Fatal infections occurred in 2.3% of patientsin the Isa-Kd group and 0.8% in the Kd group.Upper respiratory tract infection includes acute sinusitis, chronic sinusitis, H1N1 inuenza, Inrelapsedandrefractorymultiplemyelomaclinicaltrials,herpeszosterwasreportedin2%ofH3N2inuenza,inuenza,laryngitis,laryngitisviral,nasalherpes,nasopharyngitis,pharyngitis, patients.InICARIA-MM,theincidenceofherpeszosterwas4.6%intheIsa-Pdgroupcomparedpharyngotonsillitis, respiratory syncytial virus infection, rhinitis, sinusitis, sinusitis bacterial, to0.7%inthePdgroup,and,inIKEMA,incidencewas2.3%intheIsa-Kdgroupcomparedtotonsillitis, tracheitis, upper respiratory tract infection, viral rhinitis, respiratory tract infection, 1.6% in the Kd group.respiratorytractinfectionviral,inuenzalikeillness,parainuenzaevirusinfection,respiratory Cardiac failuretract infection bacterial, and viral upper respiratory tract infection. In IKEMA, cardiac failure (including cardiac failure, cardiac failure congestive, cardiac failurePneumonia includes atypical pneumonia, lower respiratory tract infection, lower respiratory acute,cardiacfailurechronic,leftventricularfailure,andpulmonaryedema)wasreportedin7%tract infection viral, pneumocystis jirovecii pneumonia, pneumonia, pneumonia inuenzal, ofpatientswiththeIsa-Kdgroup(grade 3in4%)andin7%ofpatientswiththeKdgroup(gradepneumonialegionella,pneumoniapneumococcal,pneumoniarespiratorysyncytialviral,pneu- 3 in 4.1%). Serious cardiac failure was observed in 4% of patients in the Isa-Kd group andmonia streptococcal, pneumonia viral, pulmonary sepsis, and pulmonary tuberculosis. in 3.3% of patients in the Kd group. See the current prescribing information for carlzomib forBronchitis includes bronchitis, bronchitis viral, respiratory syncytial virus bronchitis, bronchitis more information.chronic, and tracheobronchitis. 7 DRUG INTERACTIONS7.1 Laboratory Test Interference#Hypertension includes hypertension, blood pressure increased, and hypertensive crisis. Interference with Serological TestingDyspnea includes dyspnea and dyspnea exertional. SARCLISA, an anti-CD38 antibody, may interfere with blood bank serologic tests with falseCough includes cough, productive cough, and allergic cough. positive reactions in indirect antiglobulin tests (indirect Coombs tests), antibody detection(screening) tests, antibody identication panels, and antihuman globulin crossmatches inTable 6 summarizes the hematology laboratory abnormalities in IKEMA. patientstreatedwithSARCLISA[seeWarningsandPrecautions(5.4)].Inpatientswithpersistentvery good partial response, where interference is suspected, consider using an FDA-clearedisatuximab-irfc-specicIFEassaytodistinguishisatuximabfromanyremainingendogenousMprotein in the patients serum to facilitate determination of a complete response.Interference with Serum Protein Electrophoresis and Immunoxation TestsSARCLISAmay be incidentally detected by serum protein electrophoresis and immunoxationassays used for the monitoring of M-protein and may interfere with accurate response12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 4 1/5/24 4:14 PMPREPARED BY 12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FRJob info Images FontsSpecial InstructionsDate: 1-5-2024 4:14 PM isa-bplr-sl-nov23.pdf (100%; 52KB) Arial Narrow (Regular) Rename f12049085 Sarclisa US Branded 2-Page Client: NOVARTIS Journal Ad Label Update - MAT-US-2307253-v2.0Product: US SarclisaClient Code: MAT-US-2307253-v2.0-12/2023 Additional InformationWF Issue # 10351122 At Release, rename to: "12049085 Sarclisa US Releasing as: PDFx1A Branded 2-Page Journal Ad Label Update - MAT-Final Size: 7.5" x 10.5" US-2307253-v2.0"Finishing: TrimGutter: -Inks Additional Comments for SizingColors: 4C & BWBlack NoneTeamProducer: Anna VolkovaAD: Melissa PettyAE: Ian Grabowich Scale: 1"= 1"QC: LW Bleed 17" w x 11.25" h 17" w x 11.25" hProduction: Heather Cave Trim/Flat 15" w x 10.5" h 15" w x 10.5" hDigital Artist: M. 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