EU clears J&J's Darzalex as first therapy for smouldering multiple myeloma

Patients with smouldering multiple myeloma in Europe now have a proactive treatment option for the first time, thanks to a new approval from the European Commission. Johnson & Johnson's Darzalex (daratumumab) has been cleared as monotherapy for adults with high-risk smouldering multiple myeloma (HR-SMM), marking a possible shift from the current approach of simply monitoring the disease until it progresses.

"This new indication…is an exciting step forward in addressing a long-standing unmet clinical need," said Ester in 't Groen, the company's EMEA therapeutic area head for haematology, in a release Wednesday. "It means that eligible patients no longer have to live with the uncertainty or fear of waiting for progression to occur without active treatment."

The green light is specifically for the subcutaneous version of the CD38-directed antibody. J&J's EU filing drew on results from the Phase III AQUILA study, which compared fixed-duration Darzalex monotherapy against active monitoring in 390 patients.

At a median follow-up of 65.2 months, Darzalex reduced the risk of progression to symptomatic myeloma or death by 51%. The 60-month progression-free survival (PFS) rate was 63.1% in the Darzalex arm versus 40.8% for those under observation alone.

The study also demonstrated an overall survival benefit, with five-year survival rates of 93% for Darzalex-treated patients compared to 86.9% for those under active monitoring. Among the subset of patients retrospectively categorised as meeting current high-risk criteria, median PFS was not reached in the Darzalex group compared to 22.1 months with monitoring.

Questions over optimal strategy

"With today's approval, Johnson & Johnson has an innovative therapy for every stage of the disease," said Jordan Schecter, disease area leader for multiple myeloma at J&J. Darzalex is also under review for HR-SMM by the FDA.

However, the clinical community remains divided on optimal treatment strategies for HR-SMM patients. Rafael Alonso, a haematologist at Hospital Universitario 12 de Octubre in Madrid, told FirstWord following last December's American Society of Hematology (ASH) meeting that while the AQUILA results were intriguing, some questions remain unanswered.

"In this clinical trial, only about 20-25% of patients who progressed to active myeloma were rescued with a scheme that included daratumumab. This is a very, very low rate," Alonso said. In order to incorporate the drug into clinical practice for HR-SMM, he said "I would need to see data where first-line treatment of active myeloma is the four-drug regimen [Darzalex plus Velcade (bortezomib), Revlimid (lenalidomide), and dexamethasone] because that is standard clinical practice... But I could consider using this regimen for high-risk smouldering myeloma in frail patients or patients for whom I would not consider a more intensive regimen."

For the rest of that interview, see – KOL Views Q&A: Darzalex data intrigue but are not a home run in smouldering myeloma.