Darzalex Extends Time to Disease Progression, Death Among Newly Diagnosed Multiple Myeloma Patients, Phase 3 Trial Shows

Multiple myeloma patients who are not eligible for high-dose chemotherapy and stem cell transplant significantly benefit from the addition of Darzalex (daratumumab) to the standard first-line treatment of Revlimid (lenalidomide) plus dexamethasone, a Phase 3 trial shows.

The triple combination reduced the risk of disease progression or death by 45% compared to standard of care alone, and doubled the number of patients achieving a complete response to treatment.

Results from the MAIA study (NCT02252172) will be presented during the upcoming American Society of Hematology (ASH) 2018 Annual Meeting, in San Diego, California. The oral presentation, “LBA-2 Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA),” will be part of the Late-Breaking Abstracts Session on Dec. 4.

“We are extremely pleased that this new data from the important MAIA study has been chosen for presentation at the prestigious ASH annual meeting, as it will provide ASH attendees the opportunity to learn more about the transformative role of daratumumab in the treatment of newly diagnosed patients with multiple myeloma,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release.

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.

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

MAIA was designed to determine whether this combination could also improve the outcomes of previously untreated myeloma patients who were unable to receive a stem cell transplant. It included 737 patients across more than 210 centers in North America, Europe, Australia, and Israel, who received Revlimid and dexamethasone alone or in combination with Darzalex.

The ongoing study primarily aims to determine whether the Darzalex add-on extends the time patients live without experiencing signs of disease progression. Secondary measures include duration of response, complete responses, overall survival, and quality of life assessments.

Last month, Genmab announced that MAIA had met its primary endpoint, with the Darzalex combination causing a 45% reduction in the risk of disease worsening or death, compared to Revlimid and dexamethasone.

The most recent data now show that after a median follow-up of 28 months, more than half the patients receiving the Darzalex combination were still alive and progression free, while the median time patients in the control group lived without disease progression was 31.9 months.

Responses were also better in the Darzalex group, with 79.3% of patients achieving a very good partial response or better, compared to 53.1% in the standard of care group. Complete responses also doubled with Darzalex treatment, from 24.7% to 47.6%.

To date, 19% of patients have died. While the findings have not yet reached statistical significance, Darzalex seems to reduce the risk of death by 22%.

More patients receiving the triple combination experienced severe or life-threatening pneumonia, low neutrophil levels, and low levels of white blood cells. Nonetheless, its safety profile is consistent with prior Darzalex studies, and “there are no new safety signals using [Darzalex] plus [Revlimid and dexamethasone] in [newly diagnosed multiple myeloma],” researchers stated.

“These data together with the phase 3 ALCYONE study support the addition of [Darzalex] to standard of care combinations in patients with NDMM ineligible for transplant,” they concluded.