45 percent reduction in risk of death achieved with cilta-cel versus standard therapies after three-year follow-up in landmark CARTITUDE-4 study1 Data featured in a late-breaking oral presentation at the 2024 International Myeloma Society Annual Meeting1 BEERSE, BELGIUM , Sept. 27, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company, announced today long-term results from the Phase 3 CARTITUDE-4 study that show a single infusion of CARVYKTI®▼ (ciltacabtagene autoleucel; cilta-cel) significantly extended overall survival (OS) in patients with relapsed or lenalidomide-refractory multiple myeloma who have received at least one prior line of therapy, including a proteasome inhibitor (PI). Cilta-cel reduced the risk of death by 45 percent versus standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).1 With these data, cilta-cel is now the first cell therapy to improve OS versus standard therapies for patients with lenalidomide-refractory multiple myeloma as early as second line.1 Findings were featured as a late-breaking oral presentation at the 2024 International Myeloma Society (IMS) Annual Meeting, taking place in Rio de Janeiro, Brazil, from 25-28 September (Abstract #OA-65).1 “The three-year follow-up data from the Phase 3 CARTITUDE-4 study show a statistically significant and clinically meaningful improvement in overall survival and quality-of-life measures with cilta-cel versus standard therapies–meaningful results that have the potential to transform the multiple myeloma treatment landscape,” said Binod Dhakal, M.D., M.S., Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology, and study investigator.* “This adds to the growing body of data reinforcing the promise of a single infusion of cilta-cel, which, in addition to demonstrating a significant overall survival benefit, also offers patients the opportunity of a period free from multiple myeloma treatment as early as second line.” The Phase 3 CARTITUDE-4 study evaluated cilta-cel compared to standard therapies of PVd or DPd for the treatment of patients with relapsed or lenalidomide-refractory multiple myeloma after one prior line of therapy.1 Patients who received one to three prior lines of therapy, including a PI and immunomodulatory agent (IMiD), and were lenalidomide-refractory were randomised (cilta-cel, n=208; standard therapies, n=211).1 At median follow-up of almost three years (34 months), median OS for patients treated with both cilta-cel or standard therapies was not reached [NR] [(95 percent Confidence Interval [CI], not estimable (NE)-NE) and (95 percent CI, 37.75 months-NE) (Hazard Ratio [HR], 0.55; 95 percent CI, 0.39-0.79; p=0.0009)].1 At 30-month follow-up, OS rates were 76 percent for patients on the cilta-cel arm and 64 percent for patients on the standard therapies arm.1 These data show cilta-cel significantly extended OS for patients compared to standard therapies.1 In patients randomised to the cilta-cel arm, cilta-cel reduced the risk of death by 45 percent compared to standard therapies demonstrating clinically meaningful responses for patients as early as after first relapse.1 Median progression-free survival (PFS) was NR in patients treated with cilta-cel (95 percent CI, 34.50 months-NE) and 11.79 months (95 percent CI, 9.66-14.00) in patients treated with standard therapies demonstrating sustained deep and durable responses.2 Patients treated with cilta-cel had a 77 percent complete response or better, and 85 percent overall response rate.2 Patients treated with cilta-cel demonstrated a 62 percent minimal residual disease (MRD) negativity (10-5) and 57 percent MRD-negativity (10-6) compared to patients treated with standard therapies (18.5 percent, 9 percent), respectively.1 Median duration of response was NR (95 percent CI, NE-NE) in patients treated with cilta-cel and 18.69 months (95 percent CI, 12.91-23.72) for patients treated with standard therapies.2 Median time to symptom worsening based on the Multiple Myeloma Symptom and Impact Questionnaire (MySlm-Q) was NR (95 percent CI, NE-NE) with cilta-cel and 34.33 months (95 percent CI, 32.20-NE) with patients treated with standard therapies (HR, 0.38; 95 percent CI, 0.24-0.61; p<0.0001).2 “This longer-term follow up data reinforces the potential of cilta-cel to redefine outcomes, delivering results that are unprecedented in this patient population from first relapse with multiple myeloma, including a first look at overall survival,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Innovative Medicine, Johnson & Johnson. “We are striving to transform outcomes for all patients and cilta-cel is testament to our focus on advancing innovative approaches that target multiple myeloma in different ways, at every stage of the disease.” The safety profile of cilta-cel versus standard therapies was consistent with previous analysis.1 In the safety analysis (cilta-cel, n=208; standard therapies, n=208), 97 percent of patients in both arms experienced grade 3/4 treatment-emergent adverse events (TEAEs) with cytopenia being the most common.1 Treatment-emergent infections occurred in 64 percent of patients in the cilta-cel arm and 76 percent of patients who received standard therapies, with 28 percent and 30 percent being classified as grade 3/4, respectively.1 In the cilta-cel arm, there were seven patients with haematologic second primary malignancies, 50 patients died and of those patients, 21 died due to progressive disease.1 One patient treated with standard therapies experienced a haematologic second primary malignancy, 82 patients died and of those patients, 51 died due to progressive disease.1 “Cilta-cel is the first cell therapy approved for the treatment of people living with myeloma as early as second line, and now also the first cell therapy to improve overall survival and demonstrate improved patient quality-of-life outcomes versus standard therapies for patients with lenalidomide-refractory multiple myeloma,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine, Johnson & Johnson. “At Johnson & Johnson, we remain committed to addressing unmet need through the development of innovative treatments for patients and healthcare providers, and we look forward to submitting these results to local health authorities worldwide.” About CARTITUDE-4 CARTITUDE-4 (NCT04181827) is the first international, randomised, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, including a PI and an IMiDl.3 Patients were randomised to receive either a sequence of apheresis, bridging therapy, lymphodepletion and cilta-cel (n=208) or standard of care (SOC), which included PVd or DPd (n=211).4 The primary outcome measure for the study is PFS, defined as the time from the date of randomisation to the date of first documented disease progression, as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause.5 About Cilta-celIn April 2024, the European Commission (EC) approved an indication extension for cilta-cel for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an iMiD and a PI, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In April 2024, cilta-cel was approved in the U.S. for the second-line treatment of adult patients with relapsed or refractory myeloma who have received at least one prior line of therapy including a PI, an iMiD, and who are refractory to lenalidomide. For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using cilta-cel please refer to the Summary of Product Characteristics for further information.6 In line with European Medicines Agency (EMA) regulations for new medicines and those given conditional approval, cilta-cel is subject to additional monitoring.3 Cilta-cel is a B-cell maturation antigen (BCMA)-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR positive T-cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells.7,8 The cilta-cel CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.9 To date, more than 3,800 patients have been treated with cilta-cel worldwide. In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide licence and collaboration agreement with Legend Biotech USA, Inc., to develop and commercialise cilta-cel.10 About Multiple Myeloma Multiple myeloma is currently an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.11,12 In multiple myeloma, these plasma cells continue to proliferate, accumulating in the body and crowding out normal blood cells, often causing bone destruction and other serious complications.13 In the European Union, it is estimated that more than 35,000 people were diagnosed with multiple myeloma in 2022, and more than 22,700 patients died.14 While some people diagnosed with multiple myeloma initially have no symptoms, others can have common signs and symptoms of the disease, which can include bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections, or kidney problems.15,16 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at www.janssen.com/emea. Follow us at https://www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen-Cilag International NV and Janssen Research & Development, LLC are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of CARVYKTI® (ciltacabtagene autoleucel; cilta-cel). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc. Janssen Global Services, LLC, Janssen-Cilag Limited and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC, Janssen-Cilag Limited nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments. * Dr. Binod Dhakal, Associate Professor of Medicine at the Medical College of Wisconsin, Division of Hematology, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. ### 1 Mateos, et al. Overall Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update. International Myeloma Society 2024 Annual Meeting.2 Mateos, et al. Overall Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update. International Myeloma Society 2024 Annual Meeting. Abstract #OA-653 ClinicalTrials.gov. A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE4). Available at: https://clinicaltrials.gov/study/NCT04181827. Last accessed: September 2024.4 European Medicines Agency. CARVYKTI (ciltacabtagene autoleucel) Summary of Product Characteristics. September 2024.5 Arnulf, B., et al. Efficacy and safety of ciltacabtagene autoleucel ± lenalidomide maintenance in newly diagnosed multiple myeloma with suboptimal response to frontline autologous stem cell transplant: CARTITUDE-2 cohort D. 2024 ASCO Annual Meeting – American Society of Clinical Oncology. Abstract #75056 Carvykti, INN-ciltacaptagene autoleucel. Available at: https://www.ema.europa.eu/en/documents/product-information/carvykti-epar-product-information_en.pdf. Last accessed: September 2024.7 Cho SF, et al. Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy. Front Immunol 2018;10(9):1821. 8 Frerichs KA, et al. Preclinical Activity of JNJ-7957, a Novel BCMA×CD3 Bispecific Antibody for the Treatment of Multiple Myeloma, Is Potentiated by Daratumumab. Clin Cancer Res 2020;26(9):2203-22159 Tai YT, et al. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy 2015;7(11):1187-1199. 10 JnJ.com Janssen Enters Worldwide Collaboration and License Agreement with Chinese Company Legend Biotech to Develop Investigational CAR-T Anti-Cancer Therapy. Available at: https://www.jnj.com/media-center/press-releases/janssen-enters-worldwide-collaboration-and-license-agreement-with-chinese-company-legend-biotech-to-develop-investigational-car-t-anti-cancer-therapy. Last accessed: September 2024.11 Abdi J, et al. Drug resistance in multiple myeloma: latest findings on molecular mechanisms. Oncotarget 2013;4(12):2186-2207.12 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: September 2024.13 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. https://www.cancercenter.com/cancer-types/multiple-myeloma. Last accessed: September 2024.14 ECIS. European Cancer Information System. Estimates of cancer incidence and mortality in 2022, by country. Multiple myeloma. Available at: https://ecis.jrc.ec.europa.eu/explorer.php?$0-0$1-All$2-All$4-1,2$3-51$6-0,85$5-2022,2022$7-7$CEstByCountry$X0_8-3$X0_19-AE27$X0_20-No$CEstBySexByCountry$X1_8-3$X1_19-AE27$X1_-1-1$CEstByIndiByCountry$X2_8-3$X2_19-AE27$X2_20-No$CEstRelative$X3_8-3$X3_9-AE27$X3_19-AE27$CEstByCountryTable$X4_19-AE27. Last accessed: September 2024.15 American Cancer Society. What is Multiple Myeloma? https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed September 2024.16 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html. Last accessed: September 2024. CP-478017September 2024 CONTACT: Media contact:
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