Darzalex Monotherapy OK’d for Smoldering Multiple Myeloma

At its June 2025 meeting, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended extending the indications for Darzalex (daratumumab) solution for injection as monotherapy to the treatment of adult patients with smoldering multiple myeloma at high risk of developing multiple myeloma.

Darzalex is a monoclonal antibody used to treat adults with multiple myeloma and light chain amyloidosis.

Good Response to Treatment

Daratumumab attaches to the CD38 protein, found in large amounts on abnormal white blood cells in multiple myeloma and light chain amyloidosis. By attaching to CD38 on these cells, daratumumab activates the immune system to kill the abnormal white blood cells. 

Darzalex as monotherapy was investigated in two main studies involving multiple myeloma patients whose disease relapsed after, or was refractory to, at least two previous treatments, including a proteasome inhibitor and an immunomodulatory medicine. Response to treatment was measured by the disappearance of, or at least a 50% reduction in, protein produced by multiple myeloma cells. 

In the first study, around 29% of the patients who received daratumumab responded to treatment. In the second study, 36% of patients responded. In these studies, daratumumab was not compared with any other treatment. 

Full Indications

The CHMP highlighted that the full indications for Darzalex solution for injection for will now be:

For multiple myeloma:

• In combination with lenalidomide and dexamethasone or with bortezomib, melphalan, and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant
• In combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma
• In combination with bortezomib, thalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant
• In combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
• In combination with pomalidomide and dexamethasone for the treatment of adult patients with multiple 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
• As monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy

For smoldering multiple myeloma:

• As monotherapy for the treatment of adult patients with smoldering multiple myeloma at high risk of developing multiple myeloma

For light chain (AL) amyloidosis:

• In combination with cyclophosphamide, bortezomib, and dexamethasone for the treatment of adult patients with newly diagnosed systemic light chain amyloidosis

The indications for Darzalex concentrate for solution for infusion remained unchanged, the CHMP said.

Rob Hicks is a retired UK National Health Service doctor. A well-known TV and radio broadcaster, he has written several books and has regularly contributed to national newspapers, magazines, and online publications.