EC clears first treatment for high-risk smouldering multiple myeloma

Johnson & Johnson’s Janssen-Cilag has secured European Commission approval for a new indication of its subcutaneous formulation of DARZALEX (daratumumab) – making it the first authorised treatment for patients with high-risk smouldering multiple myeloma (SMM) in the EU.

The green light follows data from the Phase 3 AQUILA trial, which showed that fixed-duration daratumumab monotherapy significantly delayed disease progression and improved overall survival compared to active monitoring.

SMM is an intermediate, asymptomatic stage of multiple myeloma. While patients may not yet show typical symptoms, such as bone pain, fractures, anaemia, or kidney damage, abnormal plasma cells are already present in the bone marrow and may silently begin to cause organ damage. Around half of high-risk patients progress to active disease within two years.

“Until now, clinicians had no approved options beyond watchful waiting for this patient population,” said Professor Meletios A Dimopoulos of the National and Kapodistrian University of Athens. “By intervening earlier in the disease course, we have a meaningful opportunity to delay or prevent progression to symptomatic disease, reduce irreversible end-organ damage and extend the window of improved patient outcomes.”

The randomised, multicentre AQUILA trial enrolled 390 patients with high-risk SMM. Results of the study demonstrated that 63.1% of those treated with daratumumab remained alive and progression-free at five years, compared to 40.8% in the active monitoring group. Median progression-free survival was not reached in the treatment arm for patients classified under Mayo 2018 high-risk criteria, versus 22.1 months for controls. Overall survival at five years was also significantly higher (93.0% vs 86.9%).

Regulatory approval of daratumumab in high-risk SMM marks a milestone for J&J’s oncology franchise, extending its therapeutic footprint across all stages of multiple myeloma. “With today’s approval, Johnson & Johnson has an innovative therapy for every stage of the disease,” said Dr Jordan Schecter, Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine.

Study results also showed that the therapy’s safety profile was consistent with prior uses of daratumumab. Grade 3/4 treatment-emergent adverse events occurred in 40.4% of patients receiving daratumumab, with a low discontinuation rate of 5.7%.

The European approval may help reset expectations in how high-risk smouldering myeloma is managed, potentially shifting standard of care away from passive monitoring. “Eligible patients no longer have to live with the uncertainty or fear of waiting for progression to occur without active treatment, instead having the option to intercept the disease with therapeutic intervention,” said Ester in ’t Groen, EMEA Therapeutic Area Head, Haematology, at Johnson & Johnson.