Darzalex Combo Extends Survival in Newly Diagnosed Myeloma Patients, Phase 3 Trial Shows

Adding Darzalex (daratumumab) to the standard first-line treatment of Revlimid (lenalidomide) plus dexamethasone improves treatment and survival outcomes in multiple myeloma patients who are not eligible for an autologous stem cell transplant, a Phase 3 clinical trial shows.

Findings from the MAIA trial (NCT02252172) were published in The New England Journal of Medicine in the study, “Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma.”

It was funded in part by Janssen Pharmaceutical Companies of Johnson & Johnson, which manufactures Darzalex.

Darzalex, initially discovered by Genmab and later licensed to Janssen Biotech, is an antibody that targets CD38, a surface molecule widely produced by myeloma cells. By binding to this protein, Darzalex can stop myeloma cells from growing and kill them.

The treatment is already approved for four multiple myeloma indications, including in combination with the immunomodulatory agent Revlimid and the corticosteroid dexamethasone for patients who have received at least one prior therapy.

It is also approved as an initial treatment for myeloma patients in combination with other therapeutics, but so far, those do not include Revlimid and dexamethasone.

MAIA included 737 multiple myeloma patients recruited at more than 210 centers across North America, Europe, Australia, and Israel. The participants were newly diagnosed, had never been treated, and were not eligible for a stem cell transplant using their own stem cells.

In the trial, patients were assigned to one of two groups. Those in the control group were given Revlimid and dexamethasone, a current mainstay of myeloma treatment, while the experimental group received these two medications plus Darzalex.

After a median follow-up of 28 months, the researchers observed that 73.6% of patients receiving Darzalex remained alive and without disease worsening, compared with 61.2% in the control group. In other words, the addition of Darzalex reduced the risk of death or disease progression by 44%.

Darzalex nearly doubled the number of patients achieving a complete response — 47.6% versus 24.9% in the control group — and more than tripled those who achieved minimal residual disease negativity — 24.2% versus 7.3%. Minimal residual disease is the small number of myeloma cells that remain after treatment and may cause disease relapse.

“The MAIA study findings demonstrate a consistent and clinically meaningful treatment effect when Darzalex is incorporated into standard backbone regimens, such as lenalidomide and dexamethasone, for the initial treatment of patients with multiple myeloma who are transplant ineligible,” Craig Tendler, MD, vice president of clinical development and global medical affairs, oncology, at Janssen Research & Development, said in a press release.

Consistent with previous studies, the addition of Darzalex did increase the rates of some adverse effects, compared with the control group, most notably involving abnormally low numbers of different types of blood and immune cells, including neutrophils, lymphocytes, leukocytes, and red blood cells.

Despite this, fewer people in the Darzalex group discontinued treatment due to adverse reactions — 7.1% compared with 15.9% in the control group.

This therapeutic combination will now undergo reviews by regulatory bodies: “We have submitted applications to global health authorities in support of the MAIA data and look forward to working with regulators in the hope of bringing a new combination regimen to patients diagnosed with multiple myeloma,” Tendler said.