CHMP Recommends EU Approval of Darzalex Combo as First-line Treatment for Transplant-eligible Myeloma Patients

The Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Darzalex (daratumumab), in combination with standard pre-transplant therapy, for the treatment of newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant (ASCT).

The recommendation, based on data from the CASSIOPEIA Phase 3 trial (NCT02541383), is for a combination of Darzalex plus Velcade (bortezomib), thalidomide, and dexamethasone (collectively known as VTd), which was found to lower the risk of disease progression or death by 53% compared to VTd alone.

In the coming months, the European Commission is expected to decide whether or not to expand the existing marketing authorization for Darzalex in the EU, based on the recommendation from CHMP, an arm of the European Medicines Agency (EMA).

The U.S. Food and Drug Administration approved the treatment for a similar indication in September, after granting priority review status to Janssen‘s application.

“We are very pleased with this positive opinion from the CHMP as, if approved, the combination of Darzalex plus bortezomib, thalidomide and dexamethasone would be the first Darzalex containing regimen that would be a potential treatment option for newly diagnosed patients with multiple myeloma in Europe who are eligible for ASCT,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release.

Darzalex is an antibody that recognizes and binds CD38, a protein found at high levels on the surface of multiple myeloma cells. The medication boosts the immune response against cancer cells, leading to rapid tumor cell death. It was originally developed by Genmab, and licensed to Janssen in August 2012.

CASSIOPEIA was designed to test the effects of Darzalex in combination with standard pre-transplant therapy in a group of patients with multiple myeloma who had not received any prior treatment but were eligible for an ASCT.

The ongoing trial enrolled 1,085 patients and is divided in two parts. In part one, researchers are testing whether adding Darzalex to standard VTd improves the chances of cancer eradication, compared to VTd alone. In this part, treatment is given as preparation for the stem cell transplant, and then as a consolidation of the transplant.

In part two, all patients who responded will be reassigned to receive either maintenance therapy with Darzalex every eight weeks for up to two years, or will be kept on observation with no further treatment.

Top-line data presented at this year’s ASCO Meeting, in Chicago, showed that at 18 months of treatment, a higher percentage of patients receiving Darzalex remained alive and without signs of cancer progression, compared to those receiving VTd alone (93% versus 85%).

After consolidation therapy, Darzalex also increased the proportion of patients achieving a stringent complete response, compared to VTd alone (29% versus 20%) — another primary goal of CASSIOPEIA.

Minimal residual disease (MRD, very low number of cancer cells remaining after treatment) negativity was also higher after Darzalex treatment (64% versus 44%). MRD-negative patients had longer periods without disease worsening and better clinical outcomes.

The study is now continuing in part 2, to evaluate the benefits of Darzalex maintenance therapy in patients who responded at least partially to stem cell transplantation. CASSIOPEIA is expected to conclude in August 2024.