89 percent of patients evaluable for minimal residual disease (MRD) assessment were MRD negative, with the majority reaching MRD negativity in less than 2 months1
Results add to the overall survival (OS) benefits recently presented, as the first cell therapy to significantly extend OS versus standard therapies in multiple myeloma1,2
BEERSE, BELGIUM , Dec. 10, 2024 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, announced new results from the Phase 3 CARTITUDE-4 study that show a single infusion of CARVYKTI®▼ (ciltacabtagene autoleucel; cilta-cel) significantly increased MRD negativity rates (10-5) in patients with relapsed or refractory multiple myeloma (RRMM) who were lenalidomide refractory and had received one to three prior lines of therapy, including a proteasome inhibitor (PI), compared to standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).1 MRD is a prognostic marker of prolonged survival outcomes for patients with multiple myeloma.1 These results add to the OS benefits recently presented at the International Myeloma Society meeting earlier this year, as the first cell therapy to significantly extend OS versus standard therapies for patients with multiple myeloma.2 Findings were featured in an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting (Abstract #1032), taking place in San Diego, California, United States from 7-10 December.1
“Cilta-cel has established its significant impact on overall survival and improved progression-free survival compared to standard therapies,” said Rakesh Popat, M.D., University College London Hospitals, NHS Foundation Trust, London, UK, and lead study investigator.* “The MRD negativity results demonstrate deep responses compared to standard therapies for people living with multiple myeloma and further underscore the benefit of cilta-cel, administered as a single infusion 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 RRMM as early as 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 a median follow-up of almost three years (34 months), MRD negativity rates for evaluable patients were more than double in those treated with cilta-cel versus standard therapies (89 percent, 38 percent; p<0.0001).1 At two-and-a-half years (30 months), sustained (12 months or more), MRD-negative complete response or better in evaluable patients treated with cilta-cel was five-fold higher than that of standard therapies (52 percent, 10 percent; p<0.0001).1 A post-hoc comparison between CARTITUDE-4 and CARTITUDE-1 was also presented, comparing earlier treatment (1-3 vs 3+ prior lines of therapy) demonstrating higher rates of MRD negativity, progression-free survival (PFS) and OS rates when cilta-cel is used earlier in treatment.1
“We are encouraged by these compelling results for cilta-cel, as MRD negativity is a critical prognostic marker for prolonged progression-free and overall survival, and should be the goal of every treatment,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “Cilta-cel reflects our commitment to transforming multiple myeloma care, with a single infusion offering the potential for significantly deeper, more sustained responses that could redefine the treatment landscape for patients diagnosed with this complex disease.”
The safety profile of cilta-cel after a median follow-up of almost 34 months in the CARTITUDE-4 study was previously reported at the 2024 International Myeloma Society (IMS) Annual Meeting.2 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.2 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.2 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.2 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.2
“We are thrilled to present the latest MRD negativity results from the CARTITUDE-4 study showing that cilta-cel, the first cell therapy approved for the treatment of patients with multiple myeloma as early as second line, shows significant long-term remission rates, including progression-free survival and overall survival benefits,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. “It is also increasingly clear that reaching MRD negativity is a key goal with CAR-T therapy in myeloma, and we see that MRD rates were higher in this analysis with earlier treatment.”
Additional data on patient reported outcomes (PROs) and time to worsening (TTW) of symptoms with cilta-cel will also be presented at ASH 2024 as a poster presentation (Abstract #2002).3 Based on the Multiple Myeloma Symptom and Impact Questionnaire (MySlm-Q) system and impact domain scores, patients treated with cilta-cel reported significantly longer TTW of symptoms compared to standard therapies.2 At three-year follow up, 83 percent of patients treated with cilta-cel had not experienced worsening of functional impacts, compared to 69 percent in the standard therapies arm.3
About CARTITUDE-4
CARTITUDE-4 (NCT04181827) is the first randomised Phase 3 study evaluating the efficacy and safety of cilta-cel.4 The study compares cilta-cel with standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.4 The primary endpoint of the study is PFS; safety, OS, MRD negativity rate and overall response rate are secondary endpoints.4
About Cilta-cel
In April 2024, the European Commission (EC) approved an indication extension for cilta-cel for the treatment of adults with RRMM 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.5 In line with European Medicines Agency (EMA) regulations for new medicines and those given conditional approval, cilta-cel is subject to additional monitoring.5
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.5 BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells.6 The cilta-cel CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA.5 Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.7 To date, more than 4,000 patients have been treated with cilta-cel worldwide.8
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.9
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.10,11 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.12 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.13 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.14,15
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.innovativemedicine.jnj.com/emea. Follow us at www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen-Cilag International NV, Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., 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 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 behaviour 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 Rakesh Popat, University College London Hospitals, NHS Foundation Trust, London, UK, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.
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1 Popat, et al. Ciltacabtagene Autoleucel (Cilta-cel) vs Standard of Care (SoC) in Patients With Lenalidomide (Len)-Refractory Multiple Myeloma (MM) After 1–3 Lines of Therapy: Minimal Residual Disease (MRD) Negativity in the Phase 3 CARTITUDE-4 Trial. Oral Presentation American Society of Hematology (ASH) Annual Meeting; December 7-10, 2024.
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. September 2024.
3 Noffar, et al. Long-Term Benefits in Patient-Reported Outcomes and Time to Next Anti-Myeloma Therapy of Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care for Patients with Lenalidomide-Refractory Multiple Myeloma: Results from the Phase 3 Cartitude-4 Clinical Trial. American Society of Hematology 2024 Annual Meeting. December 2024.
4 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: December 2024.
5 EMA. Carvykti – Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/carvykti-epar-product-information_en.pdf. Last accessed: December 2024.
6 Cho, et al. Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy. Front Immunol 2018;10(9):1821.
7 Tai, et al. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy 2015;7(11):1187-1199.
8 Data on file. RF-439204. November 2024.
9 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/pressreleases/janssen-enters-worldwide-collaboration-and-license-agreement-with-chinese-company-legend-biotech-todevelop-investigational-car-t-anti-cancer-therapy. Last accessed: December 2024.
10 Abdi, et al. Drug resistance in multiple myeloma: latest findings on molecular mechanisms. Oncotarget 2013;4(12):2186-2207.
11 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: December 2024.
12 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. Available at: https://www.cancercenter.com/cancer-types/multiple-myeloma. Last accessed: December 2024.
13 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: December 2024.
14 American Cancer Society. What is Multiple Myeloma? https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Last accessed: December 2024.
15 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: December 2024.
