The MAIA trial was a clinical study investigating a therapy combination for multiple myeloma, a blood cancer that forms in plasma cells. The study focused on newly diagnosed patients who were not candidates for intensive treatments, such as a stem cell transplant. Its purpose was to determine if a new treatment approach could offer better results than the existing standard of care for this patient population.
Purpose and Design of the Study
The MAIA trial was designed to evaluate a new treatment regimen for patients with newly diagnosed multiple myeloma (NDMM) who were considered ineligible for high-dose chemotherapy and an autologous stem cell transplant. This ineligibility is often due to age, typically 65 years or older, or other health conditions that would make the procedure too risky. The goal was to see if adding a new drug to the standard two-drug therapy could lead to more effective disease control.
This international Phase 3 study was randomized and open-label, meaning patients were randomly assigned to one of two treatment groups, and both patients and doctors knew which treatment was being administered. One group received the standard treatment of lenalidomide and dexamethasone (Rd). The other group received the same Rd combination plus a third drug, daratumumab (D-Rd).
Daratumumab is a monoclonal antibody that works by targeting a specific protein called CD38 on the surface of myeloma cells. Lenalidomide is an immunomodulatory agent that helps the patient’s own immune system fight the cancer, while dexamethasone is a corticosteroid with anti-myeloma effects. The study enrolled 737 patients who were randomly assigned to either the D-Rd or Rd treatment arm.
Key Findings and Results
The trial’s primary endpoint was Progression-Free Survival (PFS), which measures the length of time a patient lives with the disease without it worsening. The results demonstrated a substantial benefit for the three-drug combination. At a median follow-up of 56.2 months, the median PFS for patients taking daratumumab, lenalidomide, and dexamethasone (D-Rd) had not yet been reached, while the median PFS for the group receiving only lenalidomide and dexamethasone (Rd) was 34.4 months.
This translated to a 47% lower risk of disease progression or death for patients in the D-Rd group. The study also examined Overall Survival (OS), which is the total time patients live after starting treatment. The five-year OS rate was significantly higher in the D-Rd group at 66.3% compared to 53.1% in the Rd group.
Beyond these measures, the trial showed that the D-Rd regimen led to deeper responses. The rate of achieving a complete response or better was 51.1% in the D-Rd group, compared to 30.1% in the Rd group. The rate of minimal residual disease (MRD) negativity, an indicator of a deep response where no cancer cells are detected with sensitive tests, was nearly three times higher in the D-Rd arm at 32.1% versus 11.1%.
Safety and Side Effects
While the three-drug regimen showed increased effectiveness, it also came with a higher incidence of certain side effects. The most common grade 3 or 4 adverse events were reported more frequently in the daratumumab, lenalidomide, and dexamethasone (D-Rd) group. Specifically, neutropenia, a condition with a low count of a type of white blood cell, was the most common, occurring in 54.1% of patients in the D-Rd arm versus 37.0% in the Rd arm.
Infections were also more common in the investigational arm, with grade 3/4 infections occurring in 42.6% of patients receiving D-Rd compared to 29.6% of those receiving Rd. Pneumonia was the most frequently reported serious infection. Other notable grade 3/4 side effects included anemia (17.0% in D-Rd vs. 21.6% in Rd) and lymphopenia (16.5% in D-Rd vs. 11.2% in Rd).
Because daratumumab is administered as an intravenous infusion, infusion-related reactions are a known side effect. These reactions, including symptoms like chills or fever, occurred in the D-Rd group but were generally manageable. The overall safety profile was considered consistent with the known profiles of the individual drugs, and no new safety concerns were identified with long-term follow-up.
Impact on Multiple Myeloma Treatment
The results of the MAIA trial had a direct influence on the standard of care for this patient population. The improvement in both progression-free survival and overall survival provided strong evidence for the superiority of the three-drug combination over the two-drug standard, prompting action from regulatory bodies.
Based on the MAIA data, the U.S. Food and Drug Administration (FDA) and other international health authorities approved the combination of daratumumab, lenalidomide, and dexamethasone (D-Rd). This approval applied to the frontline treatment of newly diagnosed patients ineligible for an autologous stem cell transplant.
This regulatory endorsement established D-Rd as a new standard of care for this group. Clinicians had a regimen proven to be more effective than the previous standard, offering patients a better chance at longer disease control and improved survival. The trial redefined the initial treatment strategy for this segment of the myeloma community.