Study demonstrates a minimal residual disease (MRD)-negativity rate of 60.9 percent and 43 percent reduction in the risk of progression or death1
Phase 3 CEPHEUS study results presented in late-breaking oral presentation at the International Myeloma Society (IMS) Annual Meeting1
BEERSE, BELGIUM, Sept. 27, 2024 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, announced today results from the Phase 3 CEPHEUS study demonstrating a significant clinical improvement with DARZALEX® (daratumumab) subcutaneous (SC) formulation in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) in the treatment of patients with newly diagnosed multiple myeloma (NDMM) who are transplant ineligible (TIE) or for whom transplant was not planned as initial therapy (transplant deferred).1 The data showing significant improvement in minimal residual disease (MRD)-negativity rate, progression-free survival (PFS) and complete response (CR) or better rate, were featured as a late-breaking oral presentation at the 21st International Myeloma Society (IMS) Annual Meeting, taking place in Rio de Janeiro, Brazil, from 25-28 September (Abstract #LBA OA-63).1
"The CEPHEUS study results show that 60 percent of patients achieved MRD-negativity, which is clinically important for physicians treating people with multiple myeloma and, in general, a strong predictor of improved long-term outcomes, including progression-free survival and overall survival,” said Saad Z. Usmani, M.D., F.A.C.P., Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center and Study Investigator.* "The subcutaneous daratumumab-based quadruplet regimen has compelling efficacy characterised by deep, durable responses and reduced risk of disease progression in the frontline population of patients not undergoing transplant, supporting the potential of this quadruplet to become a new regimen in this treatment setting.”
CEPHEUS is an ongoing, multicentre, randomised, open-label, Phase 3 study evaluating the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM patients who are TIE or transplant deferred.1 Results show that treatment with D-VRd resulted in deeper responses, including MRD-negativity, compared with VRd.1 At a median follow-up of 58.7 months, the primary endpoint was met, with overall MRD-negativity rate at a sensitivity of 10-5 (no cancer cells detected within 100,000 bone marrow cells) of 60.9 percent for patients receiving D-VRd and 39.4 percent for VRd (Odds ratio [OR], 2.37; 95 percent confidence interval [CI], 1.58-3.55; p<0.0001).1 The proportion of patients achieving sustained MRD-negativity of ≥ 12 months almost doubled with D-VRd vs VRd (48.7 percent vs 26.3 percent; OR, 2.63; 95 percent CI, 1.73-4.00; p<0.0001).1 The study also demonstrated that D-VRd significantly reduced the risk of progression or death by 43 percent (Hazard ratio [HR], 0.57; 95 percent CI, 0.41-0.79; p<0.0005) vs VRd.1 The median PFS was not reached for D-VRd vs 52.6 months for VRd.1
"Multiple myeloma is a complex disease and early intervention with treatment regimens that are well tolerated, effective and long-lasting is crucial to achieve the best outcomes for patients,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Innovative Medicine, Johnson & Johnson. "Today's data for this daratumumab-based quadruplet regimen complements data from the PERSEUS study to reinforce our unwavering commitment to deliver innovative approaches that have the potential to make a significant impact for every person with multiple myeloma from the first line of treatment, irrespective of transplant suitability.”
The daratumumab SC-based quadruplet regimen, compared to VRd, also significantly increased the depth of response with higher rates of CR or better.1 The CR or better rate was 81.2 percent with D-VRd vs 61.6 percent with VRd (OR 2.73; 95 percent CI, 1.71-4.34; p<0.0001).1 Overall survival data are not yet mature.1 The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab SC and VRd.1 The most common (>10 percent) Grade 3/4 haematologic and non-haematologic adverse events with D-VRd vs VRd were neutropenia (44.2 percent vs 29.7 percent), thrombocytopenia (28.4 percent vs 20.0 percent), anaemia (13.2 percent vs 11.8 percent), peripheral neuropathies (8.1 percent vs 8.2 percent), diarrhoea (12.2 percent vs 9.2 percent), and COVID-19 (11.2 percent vs 4.6 percent).1
"Data from PERSEUS and now CEPHEUS add to the body of evidence illustrating how the daratumumab-based quadruplet regimen has the potential to be a foundational frontline therapy across all patient types during first-line treatment, regardless of transplant eligibility status,” said Robin Carson, M.D., Global Head, Oncology, Innovative Medicine, Johnson & Johnson. "We look forward to continuing to advance this potential new quadruplet therapy and deliver on our commitment to transforming outcomes for people with multiple myeloma.”
About the CEPHEUS Study
The CEPHEUS study is being conducted in collaboration with the European Myeloma Network (EMN) as a sponsor. CEPHEUS is an international, randomised, open-label, Phase 3 study comparing subcutaneous daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRd) with standard bortezomib, lenalidomide, and dexamethasone (VRd).1 The trial enrolled 395 patients with newly diagnosed multiple myeloma who were either ineligible for stem cell transplantation (SCT) or for whom SCT is not planned.1 The primary endpoint was overall Minimal Residual Disease (MRD)-negativity rate.1 The minimum age for participation was 18 years for patients in both the D-VRd arm and VRd arm, with a median patient age of 70 (range 31-80).1 The study was conducted in 13 countries across North America, South America, and Europe.1
About Daratumumab and Daratumumab SC
Johnson & Johnson is committed to exploring the potential of daratumumab for patients with multiple myeloma across the spectrum of the disease.
In August 2012, Janssen Biotech, Inc., a Johnson & Johnson company and Genmab A/S entered a worldwide agreement, which granted Johnson & Johnson an exclusive licence to develop, manufacture and commercialise daratumumab. Since launch, daratumumab has become a foundational therapy in the treatment of multiple myeloma, having been used in the treatment of more than 548,000 patients worldwide.2 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.3 Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.3
CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.3 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.3 Daratumumab may also have an effect on normal cells.3 Data across nine Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.4,5,6,7,8,9,10,11,12
For further information on daratumumab, please see the Summary of Product Characteristics at: https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf.
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.13,14 In multiple myeloma, these malignant plasma cells continue to proliferate, accumulating in the body and crowding out normal blood cells, as well as often causing bone destruction and other serious complications.16 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.15 Whilst some patients 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 damage.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 daratumumab or daratumumab SC. 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 materialise, actual results could vary materially from the expectations and projections of Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC 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 http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen Pharmaceutica NV, Janssen-Cilag Limited, Janssen Biotech, Inc., Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
*Dr. Saad Z. Usmani M.D., F.A.C.P., Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center and Study Investigator, has provided consulting, advisory, and speaking services to Janssen; he has not been paid for any media work.
1 Usmani, S Z. et al. Daratumumab + Bortezomib/Lenalidomide/Dexamethasone in Patients With Transplant-ineligible or Transplant-deferred Newly Diagnosed Multiple Myeloma: Results of the Phase 3 CEPHEUS Study. Oral presentation. 21st International Myeloma Society (IMS) Annual Meeting. September 25 - 28, 2024.
2 Johnson & Johnson [data on file]. RF-430506. Number of patients treated with DARZALEX worldwide as of 30 June 2024.
3 Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX®▼(Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: www.businesswire.com/news/home/20200604005487/en/European-Commission-GrantsMarketingAuthorisation-for-DARZALEX%C2%AE%E2%96%BC-daratumumab-SubcutaneousFormulation-for-all-CurrentlyApproved-Daratumumab-Intravenous-Formulation-Indications. Last accessed: September 2024.
4 Moreau P, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, openlabel, phase 3 study. Lancet 2019;394(10192):29-38.
5 Facon T, et al. MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med 2019;380(22):2104-2115.
6 Mateos MV, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. The Lancet 2020;395:P132-141.
7 Dimopoulos MA, et al. APOLLO Trial Investigators. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol 2021;22(6):801-812.
8 Palladini G, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood 2020;2;136(1):71-80.
9 Chari A, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017;130(8):974-981.
10 Bahlis NJ, et al. Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study. Leukemia 2020;34(7):1875-1884.
11 Mateos MV, et al. Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Patients With Previously Treated Multiple Myeloma: Three-year Follow-up of CASTOR. Clin Lymphoma Myeloma Leuk 2020;20(8):509-518.
12 Sonneveld, P. et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2024;390(4):301-313. DOI: 10.1056/NEJMoa23120
13 Abdi J, et al. Drug resistance in multiple myeloma: latest findings on molecular mechanisms. Oncotarget 2013;4(12):2186-2207.
14 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: September 2024.
15 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.
16 American Cancer Society. Multiple myeloma: early detection, diagnosis and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Last accessed: September 2024.
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