Published on September 22, 2020
FDA Approves Daratumumab, Carfilzomib, Dexamethasone Combination Therapy
The FDA has approved another treatment for multiple myeloma. Daratumumab (Darzalex) in combination with carfilzomib (Kyprolis) and dexamethasone (DKd) has been approved to treat adult patients with relapsed/refractory multiple myeloma who have received one to three previous treatments. The approval is the eighth for Darzalex and the fifth in the relapsed/refractory setting.
"Despite ongoing advances in the treatment of multiple myeloma, the disease remains incurable and is especially challenging for patients who relapse or become refractory to established therapies," Dr. Saad Usmani, a hematologist-oncologist at Levine Cancer Institute in Charlotte, said in an August 20 press release. He is the lead investigator for CANDOR, one of the studies evaluating the targeted regimen.
Dr. Usmani added: "As a clinician, having the DKd regimen as an option means we can now combine two efficacious, targeted agents in a new, immunomodulatory drug-free triplet regimen that has demonstrated deep and durable responses for patients upon relapse.”
New Daratumumab (Darzalex)-Based Combination Regimen
Darzalex is an antibody designed to target CD38, a protein found in high numbers on the surface of multiple myeloma cells. The antibody binds to CD38 and blocks the growth of tumor cells. Kyprolis is a proteasome inhibitor — a treatment that blocks the action of proteasomes, cellular complexes that break down proteins, allowing proteins to build up and kill the myeloma cells. And dexamethasone is an anti-inflammatory medication.
Darzalex was approved in combination with two carfilzomib dosing regimens, 70 mg/m2 once weekly and 56 mg/m2 twice weekly, based on results from the ongoing Phase 3 CANDOR and Phase 1b EQUULEUS studies.
Recent results from the CANDOR study found that at a median follow-up of 17 months adding Darzalex to carfilzomib and dexamethasone lowered the risk of disease progression or death in patients by 37% and doubled the number of complete responses (28.5% vs. 10.4%), compared with the Kyprolis and dexamethasone (Kd group) alone.
At 12 months, nearly 10 times more patients given the DKd combo therapy (12.5%) showed minimal residual disease negativity, compared with those in the Kd group (1.3%).
The EQUULEUS trial, which is evaluating Darzalex in combination with multiple treatment regimens for multiple myeloma, found that 81% of patients responded to treatment for a duration of 27.5 months. Out of those responders, 14% achieved complete responses and 21% had stringent complete responses (a deeper category of complete responses).
Multiple Myeloma Clinical Trials Lead to FDA Approvals
Multiple myeloma is the second most common blood cancer in the United States, after non-Hodgkin lymphoma. There is no cure, but the prognosis has improved greatly because of more effective treatments.
On August 5, the FDA approved Blenrep belantamab mafodotin-blmf, a first-in-class treatment for adults with relapsed or refractory multiple myeloma who have received at least four prior therapies.
In May, the agency approved daratumumab and hyaluronidase-fihj (DARZALEX FASPRO) for adult patients with newly diagnosed or relapsed/refractory multiple myeloma. And March saw the approval of isatuximab-irfc (Sarclisa), in combination with pomalidomide (Pomalyst) and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies.
Still, according to Surveillance, Epidemiology, and End Results (SEER) data, published by the National Cancer Institute, the relative five-year survival rate from 2010 to 2016, was 53.9%, meaning that approximately 54 of 100 people with multiple myeloma were still alive after five years.
Is There a Cure for Multiple Myeloma?
"What I tell patients when I first started in this, I would always start off the diagnosis saying, ‘We don't have a cure for this,’” said Dr. Joshua Richter, assistant professor of medicine in The Tisch Cancer Institute at Mount Sinai in New York, in a recent Patient Power Myeloma Answers Now program.
“And what I say now is, ‘My goal is to keep you alive until there's a cure.’ And in fact, that we may have a cure today for some patients if we use the right drugs, the right technologies, and the right combinations. To me, that's been the biggest change over the last couple of years is at least how I conceptualize even curing myeloma.”
The most frequent treatment-related side effects associated with the DKd regimen were infusion-related reactions, low red blood cell counts (anemia), fatigue, high blood pressure, fever, upper respiratory tract infection, low platelet counts, low levels of different types of white blood cells, cough, shortness of breath, insomnia, headache, and back pain.
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- FDA Approves New KYPROLIS® (carfilzomib) Combination Regimen With DARZALEX® (daratumumab) And Dexamethasone In Both Once- And Twice-Weekly Dosing Regimens
- FDA approves carfilzomib and daratumumab with dexamethasone for multiple myeloma
- U.S. Food and Drug Administration Approves DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj), a New Subcutaneous Formulation of Daratumumab in the Treatment of Patients with Multiple Myeloma
- FDA Approves New Therapy for Patients with Previously Treated Multiple Myeloma
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