JnJ Darzalex gets European Commission nod for high-risk smouldering multiple myeloma

“Until now, the absence of approved therapies for high-risk smouldering multiple myeloma has left clinicians with limited options beyond observation, despite evidence that 50 percent of this patient population progress to active multiple myeloma within two years,” said Professor Meletios A. Dimopoulos, M.D., National and Kapodistrian University of Athens School of Medicine.* “The approval of daratumumab offers the potential to change this trajectory. 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.”

“This new indication for daratumumab SC is an exciting step forward in addressing a long-standing unmet clinical need for those diagnosed with high-risk smouldering multiple myeloma and is the first time a treatment has been approved for this patient population,” said Ester in ’t Groen, EMEA Therapeutic Area Head Haematology, Johnson & Johnson Innovative Medicine. “It means that 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.”

SMM is an asymptomatic intermediate disease state of multiple myeloma where abnormal cells can be detected in the bone marrow. Patients living with SMM tend not to show signs or symptoms typically associated with active myeloma, such as bone pain, bone fractures, kidney problems, or anaemia, however as abnormal plasma cells are present, organ damage may begin and progress asymptomatically. Approximately 15 percent of all cases of newly diagnosed multiple myeloma are classified as SMM, and half of those diagnosed with high-risk SMM are estimated to progress to active multiple myeloma within two years.

The Phase 3 AQUILA study (NCT03301220) is the largest randomised study of a well-defined high-risk SMM population, evaluating the efficacy and safety of fixed-duration, monotherapy daratumumab SC (n=194) compared with active monitoring (n=196). At a median follow-up of 65.2 months (range, 0-76.6), patients who received daratumumab SC showed statistically significant improved progression-free survival (PFS; defined as progression to active multiple myeloma, as assessed according to the International Myeloma Working Group diagnostic criteria for multiple myeloma [SLiM-CRAB], or death) compared to patients who underwent active monitoring; 63.1 percent in the daratumumab arm versus 40.8 percent in the active monitoring arm remained alive and progression-free at 60 months (hazard ratio [HR], 0.49; 95 percent confidence interval [CI], 0.36-0.67; p<0.001). Among patients who were retrospectively categorised as having high-risk SMM, per the current Mayo 2018 criteria (20/2/20), median PFS was not reached in the daratumumab arm and was 22.1 months in the active monitoring arm (HR, 0.36; 95 percent CI, 0.23-0.58). Overall survival was also extended with daratumumab SC, with 5-year survival rates of 93.0 percent vs 86.9 percent for active monitoring (HR, 0.52; 95 percent CI, 0.27-0.98).

Additionally, patients who received daratumumab SC saw a higher overall response rate of 63.4 percent compared to 2.0 percent with active monitoring (p<0.001). Median time to first-line multiple myeloma treatment was not reached for patients receiving daratumumab SC compared to 50.2 months with active monitoring (HR, 0.46; 95 percent CI, 0.33-0.62; nominal p<0.0001).

Daratumumab demonstrated a safety profile consistent with previous studies of daratumumab in other indications, with a low rate of treatment discontinuation due to treatment-emergent adverse events (TEAEs). Grade 3/4 TEAEs occurred in 40.4 percent of patients treated with daratumumab SC and 30.1 percent of patients actively monitored. The most common (≥5 percent in either group) Grade 3/4 TEAE was hypertension (5.7 percent vs 4.6 percent, respectively). The frequency of TEAEs leading to discontinuation of daratumumab SC was low (5.7 percent), as was the incidence of fatal TEAEs in both groups (1.0 percent vs 2.0 percent, respectively).

“Until now, there have been no approved treatment options for patients diagnosed with high-risk smouldering multiple myeloma,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. “With this approval, Johnson & Johnson has an innovative therapy for every stage of the disease. We can now offer physicians and patients the option to treat with daratumumab earlier, significantly delaying progression and the need for more intensive, continuous therapy, as well as extending overall survival. We remain steadfast in our mission to get in front of cancer.”