DARZALEX® (daratumumab)-based regimens significantly improved clinical outcomes in both transplant-eligible and -ineligible patients who are newly diagnosed with multiple myeloma

88 percent of transplant-eligible patients achieved a complete response or better, and 47 percent of patients sustained MRD-negativity for longer than one year with daratumumab subcutaneous formulation-based regimens in the Phase 3 PERSEUS study1

7.5 years median overall survival achieved with daratumumab-based regimen in Phase 3 MAIA final survival analysis is the longest reported in patients ineligible for transplant2

BEERSE, BELGIUM, June 03, 2024 (GLOBE NEWSWIRE) -- – Janssen-Cilag International NV, a Johnson & Johnson company today announced data from the Phase 3 PERSEUS study showing deepening of responses and sustained minimal residual disease (MRD) negativity at both 10-5 and 10-6 levels with a DARZALEX® (daratumumab) subcutaneous (SC) formulation in combination with bortezomib, lenalidomide and dexamethasone (D-VRd), followed by a maintenance regimen of daratumumab SC plus lenalidomide (D-R), for the treatment of patients with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM).1 The rates of deep and sustained MRD negativity were associated with improved progression-free survival (PFS) with daratumumab SC-based quadruplet regimen in these patients versus VRd.1 The data were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place in Chicago from 31 May-4 June (Abstract #7502) and will be presented at the 2024 European Hematology Association (EHA) Congress, taking place in Madrid from 13-16 June (Abstract #S201).1,2

“Our ambition is to eliminate cancer by delivering innovative options such as daratumumab, that yield deep and durable responses from first-line treatment to have the greatest impact,” said Edmond Chan, MBChB, M.D. (Res), EMEA Therapeutic Area Lead Haematology, Johnson & Johnson Innovative Medicine. “We never settle and remain focused on advancing daratumumab-based regimens to transform the experiences of multiple myeloma patients today and tomorrow.”

In the PERSEUS study, the D-VRd arm (n=355) showed deeper responses and higher rates of MRD negativity over time, at both 10-5 and 10-6 levels, compared to the VRd arm (n=354), with higher rates of complete response or better at the end of consolidation (44.5 percent vs. 34.7 percent) and maintenance (87.9 percent vs. 70.1 percent).1 Rates of MRD negativity at 10-6 increased over time and were consistently higher in the D-VRd vs. VRd arm: 43.9 percent vs. 20.9 percent (p=0.0001) at 12 months; 57.7 percent vs. 27.4 percent (p=0.0001) at 24 months, and 63.9 percent vs. 30.8 percent (p=0.0001) at 36 months.1

The D-VRd arm also demonstrated higher rates of sustained MRD negativity at 10-6 for at least 12 months, compared to the VRd arm: 47.3 percent vs. 18.6 percent (p<0.0001).1 The PFS rate at 48 months was 84.3 percent for the D-VRd arm, compared to 67.7 percent for the VRd arm (hazard ratio [HR], 0.42; 95 percent confidence interval [CI], 0.30-0.59; p<0.0001).1

The overall safety profile of D-VRd was previously presented at the 2023 American Society of Hematology (ASH) annual meeting in December and was consistent with the known safety profiles for daratumumab SC and VRd.3 The most common (>10 percent) grade 3/4 haematologic and non-haematologic adverse events (AEs) with D-VRd vs VRd were neutropenia (62.1 percent vs. 51.0 percent), thrombocytopenia (29.1 percent vs. 17.3 percent), diarrhoea (10.5 percent vs. 7.8 percent), pneumonia (10.5 percent vs. 6.1 percent), and febrile neutropenia (9.4 percent vs. 10.1 percent).3

“MRD-negativity is an important measure in predicting long-term progression-free survival for patients with multiple myeloma,” said Dr. Paula Rodriguez-Otero, Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Navarra, Spain. “The higher rates of deep and sustained MRD negativity with this daratumumab subcutaneous formulation-based regimen underscore the potential of D-VRd and D-R maintenance, to shift the treatment paradigm for transplant-eligible patients with newly diagnosed multiple myeloma, and bring us closer to the potential for a functional cure.”

Final survival analysis from Phase 3 MAIA study of daratumumab-based regimen as a frontline combination therapy to be presented at EHA

Follow-up data from MAIA showed a median overall survival (OS) of 7.5 years for daratumumab plus lenalidomide and dexamethasone (D-Rd), with a 33 percent reduction in the risk of death versus lenalidomide plus dexamethasone (Rd) in transplant-ineligible patients with NDMM (HR, 0.67; 95 percent CI, 0.55-0.82; nominal p<0.0001).2 Median OS was 90.3 months with D-Rd versus 64.1 months with Rd.2 The overall survival benefit with D-Rd verseus Rd was consistent across pre-specified subgroups.2 The median age of patients enrolled in MAIA was 73 (range: 45 to 90) years, with 43.6 percent of participants over the age of 75 years.2 These data will be presented in a poster at EHA (Abstract #P968).2

Overall, 285 (78.3 percent) and 345 (94.5 percent) patients in the D-Rd and Rd groups, respectively, discontinued study treatment, primarily due to progressive disease (119 [32.7 percent] and 141 [38.6 percent]).2

“The median overall survival of 7.5 years seen in the MAIA study reinforces the efficacy of daratumumab as a foundational treatment in the frontline setting for patients with multiple myeloma who are not eligible for transplant,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, at Johnson & Johnson Innovative Medicine. “Daratumumab has shown an overall survival benefit across three studies in newly diagnosed multiple myeloma, supporting it as a standard-of-care. Daratumumab-based quadruplet and triplet regimens have advanced outcomes for newly diagnosed patients in the transplant-eligible and ineligible settings.”

Long-term data from Phase 3 CASSIOPEIA study evaluating daratumumab-based therapy and maintenance in TE patients with NDMM to be presented at EHA

More than six-year follow-up data from CASSIOPEIA show that post-transplant maintenance with daratumumab reduced the risk of disease progression or death by 51 percent versus observation, with the median PFS not reached at six years with daratumumab vs median PFS of less than four years (45.8 months) with observation (HR, 0.49; 95 percent CI, 0.40-0.59; p<0.0001).4 Overall survival from first randomisation regardless of second randomisation was also significantly improved with D-VTd vs VTd (HR, 0.55; 95 percent CI, 0.42-0.73).4 The results will be presented in an oral presentation at EHA (Abstract #S204).4

Second primary malignancies occurred in 11.4 percent (D-VTd and daratumumab maintenance); 6.1 percent (D-VTd and observation); 12.3 percent (VTd and daratumumab maintenance) and 10.2 percent (VTd and observation) of patients, respectively.4

About the PERSEUS study

The PERSEUS study (NCT03710603) is being conducted in collaboration with the European Myeloma Network as the sponsor.5 PERSEUS is an ongoing, randomised, open-label, Phase 3 study comparing the efficacy and safety of D-VRd and autologous stem cell transplant (ASCT) followed by D-R maintenance vs VRd and ASCT followed by R maintenance in patients with TE NDMM.5 The primary endpoint is PFS, and secondary endpoints include overall complete response or better rate, overall MRD-negativity (in patients with complete response or better), and OS.5 Daratumumab SC was discontinued after at least 24 months of D-R maintenance therapy in patients who had a complete response or better and had sustained MRD-negative status for at least 12 months.5 The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.3 The study is being conducted in 14 countries in Europe and Australia.5

Data from the PERSEUS study were featured as a late-breaking oral presentation (LBA-1) at the 2023 American Society of Hematology (ASH) Annual Meeting and were simultaneously published in The New England Journal of Medicine in 2023.

About the MAIA study

The randomised, open-label, multicentre Phase 3 (NCT02076009) study included 737 newly diagnosed patients with multiple myeloma ineligible for high-dose chemotherapy and ASCT, aged 45-90 years (median age of 73).2,6 Patients were randomised to receive either D-Rd or Rd alone in 28-day cycles.6 In the D-Rd arm, patients received daratumumab 16 milligrams per kilogram (mg/kg) intraveneously (IV) weekly for cycles 1-2, every two weeks for cycles 3-6, and every four weeks for cycle 7 and thereafter.6 Patients in the D-Rd and Rd treatment arms received 25 mg of lenalidomide on days 1-21 of each 28-day cycle, and dexamethasone at 40 mg once a week for each cycle.6 Patients in both treatment arms continued until disease progression or unacceptable toxicity.6

Earlier results from the MAIA study supported the European Medicines Agency (EMA) approval of daratumumab in combination with Rd. These data were also published in The New England Journal of Medicine in 2019. An updated OS analysis was published in The Lancet Oncology in 2021.

About the CASSIOPEIA study

The randomised, open-label, multicentre, Phase 3 (NCT02541383) study is sponsored by the French Intergroupe Francophone du Myelome, in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development, LLC.7 This Phase 3 study included 1,085 newly diagnosed patients with previously untreated, symptomatic multiple myeloma, who were eligible for high-dose chemotherapy and stem-cell transplant.4,7 Part one of the study compared daratumumab in combination with VTd versus VTd induction and consolidation therapy in patients with NDMM who were eligible for ASCT and demonstrated that D-VTd yielded deeper responses and improved PFS.4,7 Part two of the study compared daratumumab maintenance therapy given every eight weeks (as a reduced frequency treatment schedule compared to the standard long-term dosing frequency of every four week) versus observation.7 The primary endpoint in this part of the study is the proportion of patients who achieve a stringent complete response 100 days after transplant.7 In the second part of the study, which is ongoing, patients who achieved a partial response or better in part one will undergo a second randomisation to receive maintenance treatment with daratumumab 16 mg/kg every eight weeks, for up to two years, or will be observed with no further treatment.7 The primary endpoint in this part of the study is PFS.7

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. Daratumumab has been approved in eight indications for multiple myeloma, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.8

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 518,000 patients worldwide.9 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.8 Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.10

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.8 Daratumumab binds to CD38 and inhibits tumour cell growth causing myeloma cell death.5 Daratumumab may also have an effect on normal cells.8 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 PFS and/or OS.11,12,13,14,15,16,17,18

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.19,20 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.20 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.21 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.22

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 and 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 actions; 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. Paula Rodriguez-Otero, Department of Hematology, Cancer Center Clínica Universidad de Navarra, has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.

Rodriguez-Otero P, et al. Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM): Analysis of minimal residual disease (MRD) in the PERSEUS trial. ASCO 2024. Oral presentation. Abstract #7502.
2 Facon T, et al. Final survival analysis of daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in transplant-ineligible patients with newly diagnosed multiple myeloma: MAIA study. EHA 2024. Abstract #P968.
3 Sonneveld P, et al. Phase 3 randomized study of daratumumab (DARA) + bortezomib, lenalidomide, and dexamethasone (D-VRd) versus VRd alone in patients (Pts) with newly diagnosed multiple myeloma (NDMM) who are eligible for autologous stem cell transplantation (ASCT): primary results of the PERSEUS trial. 2023 ASH Annual Meeting – American Society of Hematology. December 2023.
4 Moreau P, et al. Daratumumab (dara) + bortezomib/thalidomide/dexamethasone (d-vtd) followed by dara maintenance in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): >6-year update of Cassiopeia. EHA 2024. Abstract #S204.
5 ClinicalTrials.gov. Identifier NCT03710603. https://www.clinicaltrials.gov/study/NCT03710603. Last accessed: June 2024.
6 ClinicalTrials.gov Identifier NCT02076009. https://clinicaltrials.gov/ct2/show/NCT02076009. Last accessed: June 2024.
7 ClinicalTrials.gov Identifier NCT02541383. https://clinicaltrials.gov/study/NCT02541383. Last accessed: June 2024.
8 European Medicines Agency. DARZALEX Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/darzalex-epar-product-information_en.pdf. Last accessed: June 2024.
9 Janssen [data on file]. RF-412474. Number of patients treated with DARZALEX worldwide as of 31 March 2024.
10 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: June 2024.
11 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.
12 Facon T, et al. MAIA Trial Investigators. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. N Engl J Med 2019;380(22):2104-2115.
13 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.
14 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.
15 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.
16 Chari A, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017;130(8):974-981.
17 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.
18 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.
19 Abdi J, et al. Drug resistance in multiple myeloma: latest findings on molecular mechanisms. Oncotarget 2013;4(12):2186-2207.
20 American Society of Clinical Oncology. Multiple myeloma: introduction. Available at: https://www.cancer.net/cancer-types/multiple-myeloma/introduction. Last accessed: June 2024.
21 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: June 2024.
22 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: June 2024.

Media contact:
Zayn Qureshi
+44 7760 334666

Investor contact:
Raychel Kruper