The European Commission has approved the anti-CD38 antibody Darzalex (daratumumab), in combination with standard therapy, for newly diagnosed multiple myeloma patients who cannot receive a stem cell transplant.
The approval is based on data from the ALCYONE Phase 3 trial (NCT02195479), where adding Darzalex to standard of care — Velcade (bortezomib), melphalan, and prednisone (VMP) — reduced the risk of disease progression or death by half.
“Today’s approval is extremely important for multiple myeloma patients, as providing a frontline treatment option that demonstrates a deep and durable response often provides the best chance at lasting remission,” Torben Plesner, MD, the first investigator to administer daratumumab in human trials, said in a press release.
“I am proud that patients across Europe now have the option to use a monoclonal antibody as an initial therapy,” said Plesner, a professor and head of the department of hematology at Vejle Hospital in Denmark.
Darzalex is also approved in Europe as a single agent for patients who have failed prior therapies, including a proteasome inhibitor and an immunomodulatory medicine, and in combination with Revlimid (lenalidomide) and dexamethasone for patients who received at least one prior therapy.
In the United States, Darzalex is also approved, in combination with VMP, for patients with newly diagnosed myeloma unsuited for stem cell transplant. The decision was issued in May 2018.
The CD38 molecule is found in high levels on the surface of myeloma cells, regardless of disease severity. By binding CD38, Darzalex causes myeloma cells to die, both through direct cell death mechanisms and the recruitment of immune cells to the vicinity of the cancer cells.
ALCYONE, an open-label, multicenter trial, was designed to test the benefits of Darzalex add-on treatment in patients with newly diagnosed multiple myeloma who were not eligible for an autologous stem cell transplant.
The trial included 706 patients who received either Darzalex with standard VMP therapy or VMP alone. Treatment was given in nine cycles, each lasting five weeks. Patients in the Darzalex group then continued to receive Darzalex as maintenance therapy until disease progression.
Results from an interim analysis, published in the New England Journal of Medicine, showed that, 18 months after beginning treatment, more patients on the Darzalex arm remained alive and disease-free — 71.6% versus 50.2%. This represented a 50% reduction in the risk of disease progression or death.
Darzalex increased the number of patients who responded to treatment from 73.9% to 90.9%. Complete responses were nearly double in Darzalex-treated patients — 42.6% versus 24.4%.
Minimal residual disease is a measure that determines whether a patient still has myeloma cells in the blood or bone marrow that could lead to relapse. While 22.3% of patients in the Darzalex group were negative for minimal residual disease, only 6.2% of those receiving standard of care achieved this status.
Treatment with Darzalex caused serious adverse effects more often (42%) than VMP treatment (33%), researchers reported. The most common was pneumonia. Also, 28% of patients receiving Darzalex experienced infusion-related reactions caused by the medicine.
“We are incredibly grateful to the patients and physicians who participated in the clinical program for making this approval possible,” said Catherine Taylor, Europe, Middle East and Africa hematology therapeutic area lead for hematology partner Janssen. “Our mission has been to ensure daratumumab reaches as many eligible patients as possible and to prolong and improve their quality of life. This is a significant step forward.”