DARZALEX FASPRO®-based quadruplet regimen significantly improves minimal residual disease negativity for newly diagnosed multiple myeloma patients for whom transplant is not planned
Johnson & Johnson (NYSE:JNJ) announced significant results from the Phase 3 CEPHEUS study, evaluating DARZALEX FASPRO® in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for newly diagnosed multiple myeloma patients ineligible for transplant or with deferred transplant. The study showed:
- 60.9% improvement in minimal residual disease (MRD) negativity rate
- 43% reduction in the risk of progression or death
- Significantly increased depth of response with higher rates of complete response or better
At a median follow-up of 58.7 months, D-VRd demonstrated superior efficacy compared to VRd alone, with an overall MRD-negativity rate of 60.9% vs 39.4%. The study also showed a significant reduction in the risk of progression or death, with median progression-free survival not reached for D-VRd vs 52.6 months for VRd.
Johnson & Johnson (NYSE:JNJ) ha annunciato risultati significativi dallo studio di Fase 3 CEPHEUS, che valuta DARZALEX FASPRO® in combinazione con bortezomib, lenalidomide e desametasone (D-VRd) per pazienti con mieloma multiplo di nuova diagnosi non idonei per trapianto o con trapianto rinviato. Lo studio ha mostrato:
- Miglioramento del 60.9% nel tasso di negatività della malattia residua minima (MRD)
- Riduzione del 43% del rischio di progressione o morte
- Aumento significativo della profondità della risposta con tassi più elevati di risposta completa o migliore
Con un follow-up mediano di 58.7 mesi, D-VRd ha dimostrato un'efficacia superiore rispetto a VRd da solo, con un tasso di negatività MRD complessivo del 60.9% contro il 39.4%. Lo studio ha anche mostrato una riduzione significativa del rischio di progressione o morte, con una sopravvivenza mediana senza progressione non raggiunta per D-VRd rispetto a 52.6 mesi per VRd.
Johnson & Johnson (NYSE:JNJ) anunció resultados significativos del estudio Fase 3 CEPHEUS, que evalúa DARZALEX FASPRO® en combinación con bortezomib, lenalidomida y dexametasona (D-VRd) para pacientes con mieloma múltiple recién diagnosticados no elegibles para trasplante o con trasplante diferido. El estudio mostró:
- Mejora del 60.9% en la tasa de negatividad de enfermedad residual mínima (MRD)
- Reducción del 43% en el riesgo de progresión o muerte
- Aumento significativo en la profundidad de la respuesta con tasas más altas de respuesta completa o mejor
Con un seguimiento mediano de 58.7 meses, D-VRd demostró una eficacia superior en comparación con VRd solo, con una tasa general de negatividad MRD del 60.9% frente al 39.4%. El estudio también mostró una reducción significativa en el riesgo de progresión o muerte, con una supervivencia libre de progresión mediana no alcanzada para D-VRd frente a 52.6 meses para VRd.
존슨 앤드 존슨 (NYSE:JNJ)은 이식이 불가능하거나 이식을 연기한 새롭게 진단된 다발골수종 환자를 위해 보르테조밉, 레날리도마이드, 덱사메타손(D-VRd)과 함께 DARZALEX FASPRO®의 3상 CEPHEUS 연구 결과를 발표했습니다. 연구 결과는 다음과 같습니다:
- 최소 잔여 질병(MRD) 음성 비율에서 60.9% 개선
- 진행 또는 사망 위험에서 43% 감소
- 완전 반응 또는 그 이상의 비율이 크게 증가한 반응의 깊이 향상
58.7개월의 중앙 추적 관찰에서 D-VRd는 VRd 단독에 비해 우수한 효능을 나타내었으며, 전체 MRD 음성 비율이 60.9% 대 39.4%로 나타났습니다. 이 연구는 또한 D-VRd에 대해 진행 또는 사망 위험이 의미적으로 감소했으며, VRd의 경우 52.6개월에 비해 D-VRd의 중간 무진행 생존이 도달하지 않았습니다.
Johnson & Johnson (NYSE:JNJ) a annoncé des résultats significatifs de l'étude de phase 3 CEPHEUS, évaluant DARZALEX FASPRO® en combinaison avec le bortezomib, la lénalidomide et la dexaméthasone (D-VRd) pour les patients récemment diagnostiqués avec un myélome multiple et non éligibles à une transplantation ou avec une transplantation différée. L'étude a montré :
- Une amélioration de 60,9% du taux de négativité concernant la maladie résiduelle minimale (MRD)
- Une réduction de 43% du risque de progression ou de décès
- Une profondeur de réponse significativement augmentée avec des taux de réponse complète ou meilleure
Avec un suivi médian de 58,7 mois, D-VRd a démontré une efficacité supérieure par rapport à VRd seul, avec un taux de négativité général de la MRD de 60,9% contre 39,4%. L'étude a également montré une réduction significative du risque de progression ou de décès, avec une survie médiane sans progression non atteinte pour D-VRd contre 52,6 mois pour VRd.
Johnson & Johnson (NYSE:JNJ) kündigte bedeutende Ergebnisse aus der Phase-3-Studie CEPHEUS an, die DARZALEX FASPRO® in Kombination mit Bortezomib, Lenalidomid und Dexamethason (D-VRd) bei Patienten mit neu diagnostiziertem multiplem Myelom, die für eine Transplantation nicht geeignet sind oder deren Transplantation verschoben wurde, bewertet. Die Studie zeigte:
- Eine Verbesserung um 60.9% bei der Rate der negativen minimalen Resterkrankheit (MRD)
- Eine Reduktion des 43% Risikos von Progression oder Tod
- Eine signifikant erhöhte Antworttiefe mit höheren Raten für vollständige oder bessere Antworten
Bei einer medianen Nachbeobachtungszeit von 58.7 Monaten zeigte D-VRd eine überlegene Wirksamkeit im Vergleich zu VRd allein, mit einer Gesamt-MRD-Negativitätsrate von 60.9% gegenüber 39.4%. Die Studie zeigte auch eine signifikante Reduktion des Risikos für Progression oder Tod, wobei für D-VRd die mediane progressionsfreie Überlebenszeit nicht erreicht wurde, während sie für VRd bei 52.6 Monaten lag.
- 60.9% improvement in minimal residual disease (MRD) negativity rate
- 43% reduction in the risk of progression or death
- Significantly increased depth of response with higher rates of complete response or better (81.2% vs 61.6%)
- Almost doubled proportion of patients achieving sustained MRD-negativity of ≥ 12 months (48.7% vs 26.3%)
- Median progression-free survival not reached for D-VRd vs 52.6 months for VRd
- Overall survival data not yet mature
- Higher rates of Grade 3/4 adverse events in D-VRd group, including neutropenia (44.2% vs 29.7%) and thrombocytopenia (28.4% vs 20.0%)
Insights
This Phase 3 CEPHEUS study presents highly significant results for Johnson & Johnson's DARZALEX FASPRO® in treating newly diagnosed multiple myeloma patients. Key findings include:
- A
60.9% improvement in minimal residual disease (MRD) negativity rate - A
43% reduction in the risk of disease progression or death - Nearly doubled sustained MRD-negativity of ≥12 months (
48.7% vs26.3% ) - Significantly higher complete response rates (
81.2% vs61.6% )
These results demonstrate superior efficacy of the DARZALEX FASPRO®-based quadruplet regimen compared to the standard triplet therapy. The improved MRD negativity is particularly noteworthy, as it's associated with better long-term outcomes. The safety profile remains consistent with known data, suggesting a favorable benefit-risk ratio. This study positions DARZALEX FASPRO® as a potential new standard of care in frontline multiple myeloma treatment, which could significantly impact J&J's market position in oncology.
The CEPHEUS study results are highly positive for Johnson & Johnson's oncology portfolio. DARZALEX FASPRO® is already a significant revenue driver, generating
- Increased adoption and market share in newly diagnosed multiple myeloma
- Potential for label expansion and regulatory approvals
- Higher pricing power due to improved efficacy
- Extended duration of treatment, boosting per-patient revenue
While the oncology market is competitive, these results strengthen J&J's position. The subcutaneous formulation also offers a competitive advantage over intravenous alternatives. Given multiple myeloma's growing incidence and J&J's
Study of the first and only subcutaneous quadruplet regimen demonstrates 60.9 percent improvement in minimal residual disease (MRD)-negativity and 43 percent reduction in the risk of progression or death
Phase 3 CEPHEUS study results presented in late-breaking oral presentation at the International Myeloma Society (IMS) Annual Meeting
CEPHEUS is an ongoing, multicenter, randomized, open-label, Phase 3 study evaluating the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) for NDMM patients for whom transplant was not planned as initial therapy (TIE or deferred). Results show that treatment with D-VRd resulted in deeper responses, including MRD-negativity, compared with VRd. 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 (OR [odds ratio], 2.37;
"The CEPHEUS study results show that 60 percent of patients achieved MRD negativity, which is clinically important for physicians treating patients 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 characterized 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."
The DARZALEX FASPRO®-based quadruplet regimen, compared to VRd, also significantly increased the depth of response with higher rates of CR or better. The CR or better rate was 81.2 percent with D-VRd vs 61.6 percent with VRd (P<0.0001). Overall survival data are not yet mature. The overall safety profile of D-VRd was consistent with the known safety profiles for DARZALEX FASPRO® and VRd. The most common (>10 percent) Grade 3/4 hematologic and non-hematologic adverse events with D-VRd vs VRd were neutropenia (44.2 percent vs 29.7 percent), thrombocytopenia (28.4 percent vs 20.0 percent), anemia (13.2 percent vs 11.8 percent), peripheral neuropathies (8.1 percent vs 8.2 percent), diarrhea (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 DARZALEX FASPRO®-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
CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd vs VRd in patients with newly diagnosed multiple myeloma for whom autologous stem cell transplant (ASCT) is not planned as initial therapy. The primary endpoint is minimal residual disease (MRD)-negativity rate at a 10-5 sensitivity threshold. Key secondary endpoints include overall complete response (CR) or better rate, progression-free survival (PFS), and sustained MRD-negative rate at 1 year. The trial has enrolled 396 patients in 13 countries.
About the PERSEUS Study
The PERSEUS study (NCT03710603) is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for autologous stem cell transplant (ASCT). Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). 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. The study is being conducted in 14 countries in
About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the
About DARZALEX FASPRO®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.1 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.
For more information, visit https://www.darzalexhcp.com.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
- In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.
Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination,
Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.
Local Reactions
In this pooled safety population, injection-site reactions occurred in
Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer's prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.
Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient's serum. The determination of a patient's ABO and Rh blood type are not impacted.
Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥
The most common hematology laboratory abnormalities (≥
Please click here to read full Prescribing Information for DARZALEX FASPRO®.
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 https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both 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 DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). 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. 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., nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments.
*Dr. Saad Z. Usmani has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.
1 Usmani, S., et al. Daratumumab SC + Bortezomib/Lenalidomide/Dexamethasone in Patients With Transplant-ineligible or Transplant-deferred Newly Diagnosed Multiple Myeloma: Results of the Phase 3 CEPHEUS Study. IMS 2024. September 27, 2024.
2 Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
3 National Cancer Institute. Plasma Cell Neoplasms. Accessed July 2024. Available at: https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
4 Multiple Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed July 2024. Available at: https://www.cancercenter.com/cancer-types/multiple-myeloma
5 American Cancer Society. Myeloma Cancer Statistics. Accessed July 2024. Available at: https://cancerstatisticscenter.cancer.org/types/myeloma
6 American Cancer Society. What is Multiple Myeloma? Accessed July 2024. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html
7 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed July 2024. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html
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FAQ
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