New Phase 3 data for Darzalex

RARITAN, N.J.—The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the publication of data from the randomized, open-label Phase 3 MAIA study that showed Darzalex (daratumumab) plus lenalidomide and dexamethasone (Rd) resulted in a significant increase in progression-free survival (PFS) in patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT). These data were published today in The New England Journal of Medicine.

“We continue to see scientific evidence through Phase 3 studies that support the use of daratumumab in combination with standard of care regimens,” said Thierry Facon, M.D., Service des Maladies du Sang, Hôpital Claude Huriez in Lille, France, MAIA investigator and author of the study. “As multiple myeloma can become more complex at each relapse, it is important to select an optimal upfront therapy. Results from the MAIA study suggest that this daratumumab combination therapy should be considered for patients with multiple myeloma who are transplant ineligible upon diagnosis.”

Darzalex is a CD38-directed antibody. CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease. Darzalex binds to CD38 and inhibits tumor cell growth, causing myeloma cell death. The drug is being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.

According to the article, “Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population. We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation [ASCT] to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival.”

The MAIA study results demonstrated that at a median follow-up of 28 months, Darzalex in combination with Rd reduced the risk of disease progression or death by 44 percent in patients with newly diagnosed multiple myeloma who are ineligible for ASCT, compared to treatment with Rd alone. The median PFS for Darzalex-Rd has not yet been reached, compared to 31.9 months for patients who received Rd alone.

The overall response rate (ORR) was 92.9 percent in the Darzalex-Rd arm, versus 81.3 percent in the Rd arm. The addition of Darzalex resulted in near-doubling of complete response (CR), or better (47.6 percent vs. 24.9 percent). In the MAIA study, treatment with Darzalex-Rd resulted in a greater than threefold rate of minimal residual disease (MRD) negativity, compared to Rd alone (24.2 percent vs. 7.3 percent). All patients with MRD-negative status also had a response of CR or better. Patients who achieved MRD negativity demonstrated longer PFS than patients who remained MRD-positive, regardless of study treatment.

“Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among those who received lenalidomide and dexamethasone alone,” the article abstract notes. “A higher incidence of neutropenia and pneumonia was observed in the daratumumab group.”

The safety of Darzalex in combination with Rd in this patient population was consistent with previously reported studies. The most common (>10 percent) Grade 3 or 4 adverse events (AEs) in the Darzalex-Rd arm compared to Rd alone were neutropenia (50.0 percent vs. 35.3 percent), lymphopenia (15.1 percent vs. 10.7 percent), pneumonia (13.7 percent vs. 7.9 percent), anemia (11.8 vs. 19.7 percent) and leukopenia (11.0 percent vs. 4.9 percent), respectively.

AEs leading to treatment discontinuation were less frequent in the Darzalex-Rd group than with Rd alone (7.1 percent vs. 15.9 percent), despite the higher rate of neutropenia and pneumonia in the Darzalex-Rd arm. There were fewer patients who discontinued the study treatment due to infections in Darzalex-Rd versus Rd alone (0.5 percent vs. 1.4 percent). Darzalex-associated infusion-related reactions (IRR) were reported in 40.9 percent of patients (2.7 percent were Grade 3 or 4); there were no Grade 5 events. One patient discontinued treatment with Darzalex after an IRR.

“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,” said Craig Tendler, M.D., vice president, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development. “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.”