Darzalex Combo Approved in Europe to Treat Transplant-eligible Myeloma Patients

The European Commission has approved Darzalex (daratumumab), in combination with standard pre-transplant therapy, to treat newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant (ASCT).

The decision follows a positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, in December, recommending the approval of Darzalex in combination with Velcade (bortezomib), thalidomide, and dexamethasone (a regimen collectively known as VTd).

This Darzalex combination was approved the U.S. Food and Drug Administration in September.

“With this approval, newly diagnosed patients with multiple myeloma who are eligible for ASCT may have the opportunity for treatment with a Darzalex-containing regimen,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release.

“We are extremely pleased that Darzalex has received this latest approval and we look forward to the combination of Darzalex plus bortezomib, thalidomide and dexamethasone being launched in Europe,” he added.

Darzalex is an antibody that recognizes and binds to 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.

The approval was based on results from the ongoing CASSIOPEIA Phase 3 trial (NCT02541383), in which the addition of Darzalex to the VTd regimen was found to lower the risk of disease progression or death by 53% compared to VTd alone.

The study assessed the effects of Darzalex in combination with standard VTd pre-transplant therapy in a group of multiple myeloma patients who had not received any prior treatment, but were eligible for an ASCT.

CASSIOPEIA enrolled a total of 1,085 people and is divided in two parts. In part one, researchers tested whether the Darzalex combo improved the chances of cancer eradication compared to VTd alone. In this part, treatment was given as preparation for the stem cell transplant, and then as a consolidation of the transplant.

In part one, Darzalex increased the proportion of patients achieving a stringent complete response after consolidation therapy, compared to VTd alone — 29% versus 20%.

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.

In part two, now ongoing, patients who responded to the treatment are being reassigned to either maintenance therapy with Darzalex monotherapy every eight weeks for up to two years, or being kept on observation with no further treatment.

The primary goal (endpoint) of part two is the length of time patients live without signs of disease worsening (progression free survival). Topline results in secondary endpoints from part one found that more patients on Darzalex (93%) remained alive and without evidence of disease worsening for at least 18 months compared to those on VTd alone (85%).

CASSIOPEIA is expected to conclude in August 2024.