Darzalex Triple Combo Approved in Europe for Myeloma Patients Ineligible for ASCT

The European Commission has approved Darzalex (daratumumab), in combination with Revlimid (lenalidomide) and dexamethasone, as a first-line treatment for adults with multiple myeloma who are ineligible for autologous stem cell transplant (ASCT).

The decision was supported by the recent approval recommendation from the Committee for Medicinal Products for Human Use, an arm of the European Medicines Agency.

This is the fourth Darzalex regimen approved in Europe for the treatment of people with multiple myeloma, and the second for those who have just been diagnosed.

It follows similar recent decisions in the U.S. and Canada. The combination therapy also is being reviewed for the same indication in Japan.

“We are pleased that with this approval, patients in the European Union newly diagnosed with multiple myeloma who are not candidates for transplant will now have two potential options for treatment with Darzalex containing regimens,” Jan van de Winkel, PhD, Genmab’s CEO, said in a press release.

Winkel added “we look forward” to see the launch of the combination therapy in Europe.

Darzalex, created by Genmab, and developed and commercialized by Janssen Pharmaceuticals, is an antibody that binds to and blocks the activity of CD38, a protein prevalent on the surface of myeloma cells, regardless of disease severity. By binding to CD38, Darzalex not only kills cancer cells directly, but also induces an immune reaction that helps destroy the cancer.

The approval was based on the positive results of the Phase 3 MAIA trial (NCT02252172), showing the therapeutic benefits of adding Darzalex to Revlimid and dexamethasone, a standard of myeloma treatment.

MAIA recruited 737 people newly diagnosed with multiple myeloma at more than 210 centers in North America, Europe, Australia, and Israel. All were ineligible for ASCT (a stem cell transplant using their own stem cells).

Participants were assigned randomly to Revlimid and dexamethasone  treatment with or without Darzalex until the disease progressed or unacceptable adverse effects occurred.

The trial’s main goal was to determine whether the triple combo extended the time patients lived without signs of disease progression, compared with treatment without Darzalex. Secondary goals included assessing complete responses, overall survival, and minimal residual disease. This refers to the small number of myeloma cells that remain in the body after treatment and may cause disease relapse.

At a median follow-up of 28 months, adding Darzalex reduced the risk of disease progression or death by 44%, nearly doubled the number of complete responses (47.6% vs. 24.9%), and more than tripled those who were free of minimal residual disease (24.2% vs. 7.3%), compared with Revlimid and dexamethasone only.

At the time of the analysis, the median overall survival had not been reached in either group, meaning that more than half of patients in each group were still alive. Follow-up for long-term survival is ongoing.

Consistent with previous studies, adding Darzalex to standard treatment increased the rates of some adverse events (side effects). However, fewer people on triple therapy discontinued treatment due to adverse reactions (7.1% vs. 15.9%).

Janssen has a comprehensive clinical development program for Darzalex in multiple myeloma, including several Phase 3 studies. The company is planning to or currently evaluating Darzalex in other types of blood cancers with high levels of CD38, such as some lymphomas and acute lymphoblastic leukemias.