FDA OKs multiple myeloma combo for all newly diagnosed patients
Darzalex Faspro regimen now approved for those ineligible for transplant
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A treatment regimen combining Darzalex Faspro (daratumumab and hyaluronidase-fihj) with three other medications is now approved in the U.S. for all people newly diagnosed with multiple myeloma.
The combination treatment, known as D-VRd, uses Darzalex Faspro alongside Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone. It was previously authorized only for newly diagnosed myeloma patients eligible for an autologous stem cell transplant. Now, the U.S. Food and Drug Administration (FDA) has also approved the combination for patients who are not eligible for a stem cell transplant.
This is the 12th FDA-approved indication for Darzalex Faspro, according to its maker, Johnson & Johnson. The therapy recently became the first FDA-approved treatment for high-risk smoldering multiple myeloma, and J&J is currently seeking approval of a Darzalex Faspro-based combination for certain patients with advanced, hard-to-treat myeloma.
“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,” June Lanoue, U.S. president of hematology at Johnson & Johnson Innovative Medicine, said in a company press release.
The FDA’s action comes less than a year after a similar approval of the D-VRd combo in the European Union.
Awaiting a cure
“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,” Lanoue said.
Multiple myeloma is a type of blood cancer caused by the uncontrolled growth of immune cells in the bone marrow. Darzalex Faspro is an antibody-based therapy that targets CD38, a protein found on myeloma cells. It is approved for use in several myeloma treatment regimens for people with newly diagnosed disease as well as for patients with relapsed or refractory multiple myeloma who have received prior lines of therapy.
The FDA’s approval was based on data from a Phase 3 trial called CEPHEUS (NCT03652064), which enrolled nearly 400 people with newly diagnosed myeloma who were not eligible for a stem cell transplant. All participants received Velcade, Revlimid, and dexamethasone. Some received only the triple combo, while others received Darzalex Faspro as well. The study’s main goal was to determine whether adding Darzalex Faspro would improve rates of minimal residual disease (MRD) negativity, meaning a patient has no detectable cancer cells in their body.
“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,” said Saad Z. Usmani, MD, principal investigator on the trial and myeloma specialist at Memorial Sloan Kettering Cancer Center.
Results showed that, after a median follow-up of nearly two years, significantly more patients treated with Darzalex Faspro achieved MRD negativity (52.3% vs. 34.8%). After a median follow-up of more than three years, the number of patients who had been in MRD negativity for at least one year was nearly doubled among those given Darzalex Faspro (42.6% vs. 25.3%). Data also indicated that the risk of disease progression or death was reduced by about 40% in patients given Darzalex Faspro.
“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,” Usmani said.
Overall safety data from CEPHEUS were consistent with the known profiles of the four therapies used. Safety issues that were reported in at least 20% of patients given the D-VRd combo were upper respiratory tract infection, sensory nerve damage, muscle and/or bone pain, diarrhea, fatigue, swelling, rash, motor dysfunction, COVID-19, constipation, sleep disorder, cough, pneumonia, kidney impairment, dizziness, nausea, urinary tract infection, fever, abdominal pain, shortness of breath, reduced appetite, and bruising.
