The European Commission (EC) has granted marketing authorisation for the expanded use of daratumumab (Darzalex®) subcutaneous (SC) formulation in two new indications. The first authorisation of these new indications is for the use of daratumumab SC in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for the treatment of adults with newly diagnosed systemic light chain (AL) amyloidosis. This approval makes this daratumumab-based regimen the first approved therapy for AL amyloidosis in Europe.

This treatment was the first treatment approved by Food and Drug Administration (FDA) through accelerated approval for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis in January 2021.

“We are delighted about the European approval of daratumumab for AL amyloidosis. This is the first approved treatment for a group of patients with limited specific treatment options. Whilst this is an important step for European patients, there is still a lot of work to do to ensure that every AL amyloidosis patient that needs daratumumab can access it”, says Ananda Plate, CEO of Myeloma Patients Europe (MPE).

The European approval for the AL amyloidosis indication is based on positive results from the Phase 3 ANDROMEDA study, recently presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and at the 26^th European Haematology Association (EHA) Congress. The study evaluated D-VCd compared with VCd alone, a common treatment regimen used in adult patients with newly diagnosed AL amyloidosis. Patients receiving treatment with daratumumab experienced a significantly higher haematologic complete response rate (haemCR) compared to patients receiving VCd alone (59 percent vs. 19 percent). Furthermore, at 20.3 months median follow up, more patients achieved a very good partial response or better with D-VCd than VCd (79 percent vs 50 percent). Overall, D-VCd had a safety profile consistent with that previously observed for each of the agents alone.

“AL amyloidosis is a rare haematological disorder and can be incredibly challenging to diagnose as symptoms are often subtle and can mimic other conditions. This challenge is further compounded by limited treatment options,” said Efstathios Kastritis, M.D., Professor of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece and ANDROMEDA study investigator. “The approval of daratumumab is therefore welcome news for patients and the medical community as the addition of daratumumab to VCd, which has until now been the standard-of-care regimen for treating AL amyloidosis, has been shown to induce deep responses in patients, not only inducing remission at a significantly greater rate than VCd alone, but also significantly improving cardiac and renal responses and delaying major organ deterioration.”

New indication in myeloma

The second authorisation is for the use of daratumumab SC in combination with pomalidomide and dexamethasone (D-Pd) for the treatment of adults with myeloma who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or after the last therapy.

This approval is based on positive findings from the Phase 3 APOLLO study recently published in The Lancet Oncology. An updated analysis of the study, featuring health-related quality of life data, was also presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and the 26^th European Hematology Association (EHA) Congress.