Adding Darzalex to Standard Treatment for High-Risk Multiple Myeloma May Delay Disease Progression

Adding the targeted drug Darzalex (daratumumab) to standard treatment regimens for high-risk multiple myeloma may delay the time from the start of therapy until disease worsens, a study found.

Previous research had demonstrated that adding Darzalex to various “backbone regimens” for the treatment of myeloma — such as the steroid dexamethasone with either the immunomodulatory drug Revlimid (lenalidomide) or the proteasome inhibitor Kyprolis (carfilzomib) — delayed disease worsening. The recent study — a meta-analysis of previous research findings — was launched to assess whether the same principle holds true specifically in patients with high-risk disease.

The global team of researchers who collaborated on the review noted that it is unusual, yet useful, to study the effects of treatments in specific biological subgroups of patients with myeloma. They added that, because previous studies demonstrated mixed results, there was “reasonable concern that daratumumab may not improve outcomes among patients with high-risk multiple myeloma, particularly in the context of newly diagnosed disease. Given the additional toxic effects and costs associated with daratumumab, we sought to clarify its role among patients with high-risk multiple myeloma.”

The researchers concluded that adding Darzalex may delay disease progression in patients with high-risk myeloma that is recurrent, has stopped responding to previous treatments or is newly diagnosed.

Myeloma is a cancer that occurs when plasma cells in the bone marrow become abnormal and grow out of control, crowding out normal blood-forming cells. High-risk myeloma has specific genetic abnormalities: a switching of genetic material between chromosomes 4 and 14; a switching of genetic material between chromosomes 14 and 16; or the deletion of genetic material from chromosome 17. These abnormalities are associated with a worse prognosis.

Darzalex (daratumumab) is a monoclonal antibody that inhibits the activity of the protein CD38, which is present on the surface of myeloma cells; this directly kills the cancer cells or stimulates the immune system to do so.

To conduct the meta-analysis, the researchers, led by Dr. Smith Giri at the University of Alabama at Birmingham, considered the results of six phase 3 trials that compared patient health outcomes when a backbone regimen was administered with or without Darzalex. Three of the trials focused on patients with newly diagnosed myeloma (2,528 patients, 358 of them with high-risk disease) and three included patients with recurrent or treatment-resistant disease (1,533 patients, 222 of them with high-risk myeloma).

Among patients with newly diagnosed disease, those who received Darzalex with their treatment regimen experienced a 33% improvement in the time until disease progression compared with patients who received a backbone regimen without Darzalex. Those results were not considered statistically significant. In the three trials focused on patients with recurrent or resistant disease, those who received treatment including Darzalex experienced a 55% improvement in the time until disease progression compared with those treated without the study drug; results from two out of the three trials in this population were considered statistically significant. In all six trials, patients with standard-risk myeloma experienced significantly improved time until disease progression.

Based on those findings, the researchers determined that the addition of Darzalex is associated with a longer delay in disease progression in patients with high-risk multiple myeloma.

“The findings from this systematic review and meta-analysis suggest that incorporating daratumumab into backbone myeloma regimens is associated with significantly improved progression-free survival for patients with newly diagnosed high-risk multiple myeloma or relapsed or refractory high-risk multiple myeloma,” the authors wrote. “Furthermore, the benefit appears to be consistent irrespective of the backbone anti-myeloma regimen. These findings are of direct clinical relevance and may help clinicians choose an optimal anti-myeloma regimen for patients with high-risk cytogenetic factors.”

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