Patients at high risk for developing multiple myeloma who received the drug daratumumab for up to three years saw a 51% reduction in their risk of disease progression compared with similar patients who were actively monitored but not treated.

“Compared with active monitoring, single-agent treatment with daratumumab had an acceptable safety profile and showed a clinically meaningful benefit in preventing or delaying progression to active multiple myeloma in high-risk patients,” said principal investigator Meletios A. Dimopoulos, MD, professor and chairman of the department of clinical therapeutics at the National and Kapodistrian University of Athens School of Medicine. “These results represent a new option for high-risk patients and their physicians to consider when weighing the pros and cons of treatment versus active monitoring.”

Patients enrolled in the AQUILA study, a randomised phase III clinical trial conducted in 24 countries, had been diagnosed with high-risk smouldering multiple myeloma, a precancerous condition with features that put them at more than 50% risk of developing active cancer within two years. The decision to treat these patients or not is controversial among haematologists. Active monitoring, in which patients are closely evaluated by their doctors for any signs that their condition is getting worse, is currently the standard of care.

A total of 390 patients were enrolled. Patients’ median age was 64 and 48% were men. Patients were randomly assigned to receive either subcutaneous daratumumab every 28 days or active monitoring for up to 36 months or until their condition progressed to multiple myeloma, whichever came first.

The study’s primary endpoint was the elapsed time between randomisation to treatment and a multiple myeloma diagnosis. Disease progression was assessed by an independent review committee using internationally accepted diagnostic criteria. Secondary endpoints included patients’ overall response rate, progression free survival on first-line treatment, and overall survival.

After a median follow-up of 65.2 months (about five and a half years), Dimopoulos and his colleagues estimated that 63.1% of the patients assigned to daratumumab had not progressed to active multiple myeloma at five years, compared with 40.8% of those assigned to active monitoring. For patients who received active monitoring, the median time to a multiple myeloma diagnosis was 41.5 months (about three and a half years).

The overall response rate was 63.4% among patients receiving daratumumab, compared with 2.0% for those being actively monitored. In the daratumumab group, 33% of patients began treatment for active multiple myeloma, compared with 52% of those in the active monitoring group.

Adverse events requiring treatment occurred in 40.4% of patients who received daratumumab, compared with 30.1% of those who were actively monitored. In both groups, the most common moderate-to-severe adverse effect was high blood pressure. A total of 41 patients died, 15 (7.7%) of those treated with daratumumab, compared with 26 (13%) who received active monitoring. This difference was statistically significant.

“This is the first study to show improved outcomes with an agent that is not chemotherapy in patients with a myeloma-related condition. Furthermore, the observed benefit in the overall survival of the daratumumab-treated patients is very encouraging,” Dr. Dimopoulos said.

Daratumumab is a biologic therapy made from living cells that works by attaching to proteins found on the surface of cancer cells. It both kills cancer cells directly and stimulates cells from the patient’s immune system to multiply and kill cancer cells. Daratumumab is approved by the U.S. Food and Drug Administration for use either alone or in combination with standard-of-care drug regimens for patients with newly diagnosed multiple myeloma or myeloma that has come back or not responded to other treatments.

Dr. Dimopoulos cautioned that the findings apply only to patients whose smouldering multiple myeloma has specific features that place them at the highest risk for developing active cancer. Future studies should test whether using daratumumab in combination with other agents can further improve outcomes for these patients, he said.

This study was funded by Janssen Research & Development, LLC, a sister company of Janssen Biotech, Inc., which manufactures daratumumab. Both companies are subsidiaries of Johnson & Johnson.

The study was simultaneously published in the New England Journal of Medicine.

Source: ASH