DARZALEX FASPRO® quadruplet approved in U.S. for transplant-ineligible newly diagnosed multiple myeloma
Johnson & Johnson announced today the U.S. Food and Drug Administration (FDA) approved DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplant (ASCT). D-VRdis the only anti-CD38 antibody-based regimen with approved indications across newly diagnosed patients, regardless of transplant eligibility.
The pivotal Phase 3 CEPHEUS study (NCT03652064) evaluated the efficacy and safety of D-VRd compared to bortezomib, lenalidomide and dexamethasone (VRd) in NDMM patients who were ineligible for ASCT or deferred ASCT as initial therapy.1 Today’s milestone follows approval for D-VRd for the treatment of patients who are newly diagnosed with multiple myeloma and eligible for ASCT.2
“D-VRd increased the depth and durability of responses, significantly reduced the risk of disease progression or death, and nearly doubled the rate of sustained minimal residual disease (MRD)-negativity compared to VRd in patients ineligible for ASCT, solidifying this regimen as a potential standard of care for newly diagnosed patients with multiple myeloma,” said Saad Z. Usmani, M.D., Chief, Myeloma Service, Memorial Sloan Kettering Cancer Center and CEPHEUS principal investigator.* “MRD-negativity is a potential predictor of prolonged progression-free and overall survival and D-VRd is now the only quadruplet regimen approved by the FDA based on a study with MRD-negativity as a primary endpoint.”
“This approval marks the twelfth indication for DARZALEX FASPRO overall and fifth in newly diagnosed multiple myeloma, underscoring its role as foundational therapy for both newly diagnosed and relapsed/refractory patients,” said June Lanoue, U.S. President, Hematology, Johnson & Johnson Innovative Medicine. “CEPHEUS demonstrated the efficacy of a DARZALEX FASPRO-based quadruplet as a frontline standard of care. With this approval, patients can receive D-VRd when they are first diagnosed with multiple myeloma, an important milestone as we work to one day deliver a functional cure.”
Findings from CEPHEUS showed that at a median follow-up of 22 months, the overall MRD-negativity rate at a sensitivity of 10-5 (no cancer cells detected within 100,000 bone marrow cells) was 52.3 percent vs 34.8 percent with VRd (P<0.0005).1 At a median follow-up of 39 months, the proportion of patients achieving sustained MRD-negativity of ≥12 months almost doubled at 42.6 percent vs 25.3 percent (P<0.0003) and D-VRd also significantly reduced the risk of progression or death by 40 percent (hazard ratio [HR], 0.60; 95 percent confidence interval [CI], 0.41-0.88; P<0.0078) vs VRd.
At a median follow-up of nearly 5 years (59 months), D-VRd significantly increased the depth of response with higher rates of complete response or better at 81.2 percent vs 61.6 percent with VRd.1 Overall survival data were not yet mature.1 The effectiveness of D-VRd has not been established in patients who refused ASCT as initial therapy.
The overall safety results of DARZALEX FASPRO®+VRd were consistent with the adverse reactions seen for DARZALEX FASPRO® and VRd.1 In the CEPHEUS study, the most common adverse events (≥20%) in patients with newly diagnosed multiple myeloma who received D-VRd were upper respiratory tract infection, sensory neuropathy, musculoskeletal pain, diarrhea, fatigue, edema, rash, motor dysfunction, COVID-19, constipation, sleep disorder, cough, pneumonia, renal impairment, dizziness, nausea, urinary tract infection, pyrexia, abdominal pain, dyspnea, decreased appetite, and bruising.1
About the CEPHEUS Study
CEPHEUS (NCT03652064) is a multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd vs VRd in patients with newly diagnosed multiple myeloma who were ineligible for autologous stem cell transplant (ASCT) or refused ASCT as initial therapy. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10-5 sensitivity threshold. Secondary endpoints include complete response or better rate, progression-free survival (PFS), sustained MRD-negativity rate, MRD-negative rate at 1-year, overall response rate, time to and duration of response, PFS on next line of therapy, overall survival and safety. The trial enrolled 395 patients in 13 countries across North America, South America, and Europe.
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.3 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.4 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.5 In 2026, it is estimated that more than 36,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.6
People with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.7,8
About DARZALEX FASPRO® and DARZALEX®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eleven indications in multiple myeloma, five 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.
DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible. DARZALEX® is the first CD38-directed antibody approved to treat multiple myeloma.
DARZALEX®-based regimens have been used in the treatment of more than 720,000 patients worldwide. 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.
Source Link: https://www.jnj.com/
