b'B:17"T:15"S:14.5"For your adult patients with relapsed or refractory multiple myelomaSARCLISA + Kd Was Studied in Patients Like Alice 1Alices patient information Proportion of patients in IKEMA1-6 * 1 prior line of therapy 44 %2L1L: VRd inductionASCTVR maintenance*Based on a review of published phase 3 trials that included lenalidomide-refractory patients with RRMM. Interpret with caution, as VGPR for 13 months posttransplantvarious factors, including patient population, differ between trials.Refractory to lenalidomide 33 %Final analysis: mPFS 41.7 months with SARCLISA + Kd (n=179) vs 20.8 months with Kd alone (n=123), HR=0.59 68 years of ageRapid, aggressive disease progression on lenalidomide SARCLISA + Kd (95% CI: 0.42, 0.83) at a median follow-up of 44 months2 Hypothetical patient case. maintenanceIKEMA Interim analysis: mPFS NR with SARCLISA + Kd vs 20.27 months with Kd alone, HR=0.548 (95% CI: 0.37,Positive for 1q21+ 42 %1De ned as high risk by the National Comprehensive Cancer 0.82; P=0.0032) at a median follow-up of 20.7 months Network (NCCN), IMWG, and mSMART guidelines8-10Consider SARCLISA + Kd for your patients with RRMM who have high-risk factors like Alice. 1IKEMA study design (SARCLISA + Kd): A multicenter, multinational, randomized, open-label, 2-arm, phase 3 study evaluated the ef cacySee her full patient pro le at sarclisahcp.comand safety of SARCLISA in 302 patients with RRMM who had received 1 to 3 prior therapies. Patients received either SARCLISA 10 mg/kgSanofi Sarclisaadministered as an IV infusion in combination with Kd (n=179) or Kd alone (n=123), administered in 28-day cycles until disease progression or unacceptable toxicity. SARCLISA was given weekly in therst cycle and every 2 weeks thereafter. PFS was the primary endpoint; ORR, [2 of 6]1,7 Important Safety Information (contd) pregnant women of the potential risk to a fetus. Advise females VGPR, CR, MRD-, and OS were key secondary endpoints. with reproductive potential to use an effective method of PFS results were assessed by an IRC, based on central laboratory data for M-protein, and central radiologic imaging review using the IMWG criteria. An interim analysis was conductedLaboratory Test Interference contraception during treatment with SARCLISA and for 5 months when 65% of the 159 PFS events (ie, 103 events) were observed. P value is not reported as this is a non-inferential analysis of the primary endpoint that was met at the time of the Interference with Serological Testing (Indirect Antiglobulin Test) after the last dose. The combination of SARCLISA with pomalidomide interim analysis.1,7 SARCLISA binds to CD38 on red blood cells (RBCs) and may result inis contraindicated in pregnant women because pomalidomide may Indication increased to the initial rate, and then increased incrementally. In casea false-positive indirect antiglobulin test (indirect Coombs test). Thecause birth defects and death of the unborn child. Refer to the SARCLISA (isatuximab-irfc) is indicated: symptoms do not improve to grade 1 after interruption of SARCLISAindirect antiglobulin test was positive during Isa-Kd treatment inpomalidomide prescribing information on use during pregnancy.infusion, persist or worsen despite appropriate medications, or63% of patients. In patients with a positive indirect antiglobulin test,ADVERSE REACTIONSIn combination with car lzomib and dexamethasone, for therequire hospitalization, permanently discontinue SARCLISA andblood transfusions were administered without evidence of hemolysis. treatment of adult patients with relapsed or refractory multipleinstitute appropriate management. Permanently discontinueABO/RhD typing was not affected by SARCLISA treatment. The most common adverse reactions (20%) in patients receiving myeloma who have received 1 to 3 prior lines of therapy SARCLISA if an anaphylactic reaction or life-threatening (grade 4)Isa-Kd were upper respiratory tract infection, infusion-related IRR occurs and institute appropriate management. Before therst SARCLISA infusion, conduct blood type and screenreactions, fatigue, hypertension, diarrhea, pneumonia, dyspnea,S:10" T:10.5" B:11.25"Important Safety Information tests on SARCLISA-treated patients. Consider phenotyping prior toinsomnia, bronchitis, cough, and back pain. The most common CONTRAINDICATIONSNeutropeniastarting SARCLISA treatment. If treatment with SARCLISA hashematology laboratory abnormalities (80%) were decreased SARCLISA is contraindicated in patients with severe hypersensitivitySARCLISA may cause neutropenia.already started, inform the blood bank that the patient is receivinghemoglobin, decreased lymphocytes, and decreased platelets.to isatuximab-irfc or to any of its excipients. In patients treated with Isa-Kd, neutropenia occurred in 55% ofSARCLISA and that SARCLISA interference with blood compatibilitySerious adverse reactions occurred in 59% of patients receiving patients, with grade 3-4 neutropenia in 19% of patients (grade 3 intesting can be resolved using dithiothreitol-treated RBCs. If anIsa-Kd. The most frequent serious adverse reactions in 5% of WARNINGS AND PRECAUTIONS18% and grade 4 in 1.7%). Neutropenic complications occurred in 2.8%emergency transfusion is required, noncross-matched ABO/RhD- patients who received Isa-Kd were pneumonia (25%) and upper Infusion-Related Reactionsof patients, including febrile neutropenia (1.1%) and neutropeniccompatible RBCs can be given as per local blood bank practices. respiratory tract infections (9%). Adverse reactions with a fatal Serious infusion-related reactions (IRRs), including life-threateninginfections (1.7%). Interference with Serum Protein Electrophoresis andoutcome during treatment were reported in 3.4% of patients in the anaphylactic reactions, have occurred with SARCLISA treatment.Monitor complete blood cell counts periodically during treatment.Immuno xation Tests Isa-Kd group (those occurring in more than 1% of patients were Severe signs and symptoms include cardiac arrest, hypertension,Consider the use of antibacterial and antiviral prophylaxis duringSARCLISA is an IgG kappa monoclonal antibody that can bepneumonia occurring in 1.7% and cardiac failure in 1.1% of patients).hypotension, bronchospasm, dyspnea, angioedema, and swelling. treatment. Monitor patients with neutropenia for signs of infection.incidentally detected on both serum protein electrophoresis andUSE IN SPECIAL POPULATIONSIn IKEMA, infusion-related reactions occurred in 46% of patientsIn case of grade 4 neutropenia, delay SARCLISA dose until neutrophilimmuno xation assays used for the clinical monitoring of count recovery to at least 1 x 109/L, and provide supportive careendogenous M-protein. This interference can impact the accuracyBecause of the potential for serious adverse reactions in the treated with SARCLISA, car lzomib, and dexamethasone (Isa-Kd).breastfed child from isatuximab-irfc administered in combination In the Isa-Kd arm, the infusion-related reactions occurred on thewith growth factors, according to institutional guidelines. No doseof the determination of complete response in some patients withwith pomalidomide, advise lactating women not to breastfeed infusion day in 99% of episodes. In patients treated with Isa-Kd, 95%reductions of SARCLISA are recommended. IgG kappa myeloma protein. during treatment with SARCLISA.of those experiencing an infusion-related reaction experienced itSecond Primary Malignancies Embryo-Fetal Toxicityduring therst cycle of treatment. All infusion-related reactionsThe incidence of second primary malignancies is increased inBased on the mechanism of action, SARCLISA can cause fetal harmPlease see Brief Summary of full Prescribing Information on the resolved: within the same day in 74% of episodes, and the day afterpatients treated with SARCLISA-containing regimens. The overallwhen administered to a pregnant woman. SARCLISA may causefollowing pages.in 24% of episodes. incidence of second primary malignancies in all the SARCLISA- fetal immune cell depletion and decreased bone density. Advise The most common symptoms (5%) of an infusion-related reactionexposed patients was 4.1%.in clinical trials of SARCLISA in relapsed or refractory multipleIn the ongoing IKEMA study, at a median follow-up time of 21References: 1. SARCLISA [prescribing information]. Bridgewater, NJ: sano -aventis U.S. LLC. 2. Martin T, Dimopoulos MA, Mikhael J, et al. Isatuximab, car lzomib, and dexamethasone in myeloma (N=329) included dyspnea, cough, nasal congestion, andmonths, second primary malignancies occurred in 7% of patients inpatients with relapsed multiple myeloma: updated results from IKEMA, a randomized phase 3 study. Blood Cancer J. 2023;13:72. doi:10.1038/s41408-023-00797-8 3. Hernndez-Rivas JA, nausea. Anaphylactic reactions occurred in less than 1% of patients.the Isa-Kd arm and in 4.9% of patients in the Kd arm. Ros-Tamayo R, Encinas C, Lahuerta JJ. The changing landscape of relapsed and/or refractory multiple myeloma (MM): fundamentals and controversies. Biomarker Res. 2022;10(1):1-23. To decrease the risk and severity of IRRs, premedicate patients4. Usmani SZ, Quach H, Mateos MV, et al. Car lzomib, dexamethasone, and daratumumab versus car lzomib and dexamethasone for patients with relapsed or refractory multiple prior to SARCLISA infusion with acetaminophen, H 2antagonists,The most common (1%) second primary malignancies in clinicalmyeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23:65-76. 5. Orlowski RZ, Nagler A, Sonneveld P, et al. Randomized diphenhydramine or equivalent, and dexamethasone. trials of SARCLISA in relapsed or refractory multiple myeloma (N=329)phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to included skin cancers (5% with SARCLISA-containing regimens andprogression. J Clin Oncol. 2007;25(25):3892-3901. 6. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med.Monitor vital signs frequently during the entire SARCLISA infusion.2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614 7. Data onle. sano -aventis U.S. LLC. 8. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN For patients with grade 2 reactions, interrupt SARCLISA infusion2.6% with comparative regimens) and solid tumors other than skinGuidelines ) for Multiple Myeloma V.3.2023.National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed December 19, 2022. To view the most recent and complete and provide appropriate medical management. For patients withcancer (3% with SARCLISA-containing regimens and 1.8% withversion of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their comparative regimens). All patients with non-melanoma skinapplication or use in any way. 9. Sonneveld P, Avet-Loiseau H, Lonial S, et al. Treatment of multiple myeloma with high-risk cytogenetics: a grade 2 or grade 3 reactions, if symptoms improve to grade 1,cancer continued treatment after resection of the skin cancer. consensus of the International Myeloma Working Group. Blood. 2016;127(24):2955-2962. 10. Mayo Clinic. Treatment of relapsed myeloma. restart SARCLISA infusion at half of the initial infusion rate, withMonitor patients for the development of second primaryAccessed January 17, 2023. https://www.msmart.org/mm-treatment-guidelinessupportive care as needed, and closely monitor patients. Ifmalignancies.symptoms do not recur after 30 minutes, the infusion rate may be 1L= rst line; 2L=second line; ASCT=autologous stem cell transplant; CR=complete response; IMWG=International Myeloma Working Group; IRC=independent response committee; IV=intravenous; Kd=car lzomib and dexamethasone; M-protein=monoclonal protein; mPFS=median progression-free survival; MRD-=minimal (or measurable) residual disease negativity; mSMART=Mayo Clinic 2023 sanofi-aventis U.S. LLC. All rights reserved. SARCLISA and Sanofi are registered trademarks of Sanofi or an affiliate. Strati cation for Myeloma and Risk-adapted Therapy; NR=not reached; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; RRMM=relapsed or refractory multipleAll the other trademarks above are the property of their respective owners, who have no affiliation or relationship with Sanofi. myeloma; VGPR=very good partial response; VR=bortezomib and lenalidomide; VRd=bortezomib, lenalidomide, dexamethasone. MAT-US-2307253-v2.0-12/2023FS:7" FS:7"F:7.5" F:7.5"12049085_SAR_US_Branded_2_Page_Journal Ad_A_M4FR.indd 1 1/5/24 4:14 PMPREPARED BY12049085-vc12049124 US Branded 2-Page Journal Ad (A-size) Label Update M4FRJob info Images FontsSpecial InstructionsDate: 1-5-2024 4:14 PM SANO_A091087_4C.psd (CMYK; 558 ppi;Greycliff CF (Regular, Demi Bold Oblique, Bold,Rename f12049085 Sarclisa US Branded 2-Page Client: NOVARTIS 62.67%; 65.5MB), 42_lockup-no_circle_4C. Regular Oblique, Demi Bold, Bold Oblique), MarkJournal Ad Label Update - MAT-US-2307253-v2.0Product: US Sarclisa ai (28.06%; 929KB), 220110_SANOFI_LOGO_ Pro (Regular), Arial Narrow (Regular)Client Code: MAT-US-2307253-v2.0-12/2023 CMYK.ai (8.45%; 2.9MB), SANO_A073862_4C. 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