Darzalex Combos Might Be More Efficient When Used Early in Myeloma

Patients with relapsed or treatment-resistant multiple myeloma, who have undergone several earlier treatment rounds, have a much poorer response to combination treatments including Darzalex (daratumumab) than what has been reported in clinical trials, according to an analysis by the Mayo Clinic.

Nevertheless, the research team underscored that Darzalex-containing combination treatments are effective in heavily pre-treated patients who are largely ineligible for clinical trials, and whom physicians are likely to encounter in their daily practice.

But earlier use of the treatment approach might turn out to be even more effective, they said.

The study, “Efficacy of daratumumab-based therapies in patients with relapsed, refractory multiple myeloma treated outside of clinical trials,” was published in the American Journal of Hematology.

Patients who have failed numerous earlier treatments often are not eligible for clinical trials. Because their treatment outcomes might differ from that reported in studies, the research team analyzed data from 126 patients who received one or more cycles of any Darzalex-containing combination treatment.

Darzalex is approved for the treatment of relapsed or refractory myeloma in combination with Revlimid (lenalidomide), Velcade (bortezomib), Pomalyst (pomalidomide), and dexamethasone.

The patient group had a median age of 67 years, but ages ranged from 43-93 years. One-third of them had high-risk type cancer. The median number of previous treatments was four, but some patients had received up to 14 treatments.

Although the median time to Darzalex combination therapy was 4.3 years, some patients received it within a year, while others waited 13 years.

The most common combination was Darzalex with Pomalyst and dexamethasone, followed by Revlimid and dexamethasone, and Velcade plus dexamethasone. Among them, 13 percent were refractory to Darzalex when used on its own.

Researchers followed the group for a median of 5.5 months, and analyses showed that 47 percent responded to the treatment.

Although progression-free survival was a median of 5.5 months for the entire group, the study demonstrated that the time it took for patients to progress was heavily influenced by their treatment history.

Patients refractory to five earlier treatments had the worst progression-free survival of only 2.2 months, followed by those refractory to four earlier therapies, who lived for 3.1 months before progressing.

Those who did not respond to treatment with one or more of the drugs in the combination treatments had a progression-free survival of 4.9 months, while those who did not have such resistance issues lived for a median of 8.9 months before their disease progressed.

Patients who received fewer than two earlier therapies had the best outcomes, with median progression-free survival not reached during the study.

The findings indicate that Darzalex-based combinations in multiple myeloma might be more beneficial if used early on in the disease course.

Clinical trials exploring Darzalex combinations as a first-line treatment in multiple myeloma patients who had not received previous cancer therapy are ongoing, and may provide evidence that changes treatment practice in myeloma, researchers said.