In patients with newly diagnosed multiple myeloma (MM) who were ineligible for autologous hematopoietic cell transplantation (AHCT), adding daratumumab to a regimen of lenalidomide and dexamethasone (Rd) reduced the risk of disease progression or death by 44%, compared with Rd alone. This is according to results from the phase III MAIA trial published in the New England Journal of Medicine.
However, lead author Thierry Facon, MD, from the University of Lille and Centre Hospitalier Universitaire in France, and researchers noted that patients treated with daratumumab also had a higher incidence of neutropenia and pneumonia than those who received Rd alone. (Editor’s note: Results from the phase III MAIA trial recently supported the U.S. Food and Drug Administration’s approval of daratumumab plus lenalidomide and dexamethasone for the treatment of patients with newly diagnosed, transplant-ineligible MM.)
The randomized, open-label phase III MAIA trial enrolled 737 adults with previously untreated MM who were considered ineligible for high-dose chemotherapy with AHCT – primarily due to age (≥65 years) or comorbidities.
Participants were stratified according to disease stage (per International Staging System [ISS] stage), region, and age <75 vs. ≥75 years), then randomized 1:1 to receive either:
- Rd: lenalidomide 25 mg daily on days 1-21 and dexamethasone 40 mg weekly in 28-day treatment cycles (n=369)
- Rd plus daratumumab
- 16 mg/kg weekly (n=368)
The researchers noted that demographic and clinical characteristics were well balanced between the groups: Median age was 73 years (range = 45-90 years), and 14.3% of patients had a high-risk cytogenetic profile. The median time since MM diagnosis was 0.9 months (range = 0-14.5 months).
At the time of the clinical data cutoff for the primary analysis (September 24, 2018), approximately one-third of patients in the daratumumab group (n=118; 32.4%) and more than half of patients in the control group (n=207; 56.7%) had discontinued treatment. Discontinuations were most commonly related to progressive disease (14.6% in the daratumumab group and 23.8% in the control group), followed by adverse events (AEs; 7.4% and 16.2%, respectively).
“These findings can be added to those from a growing list of trials that support the use of daratumumab-based regimens.”
—Thierry Facon, MD
The median duration of treatment was 25.3 months (range = 0.1-40.4 months) in the daratumumab group and 21.3 months (range = 0.03-40.6 months) in the control group.
The most common AEs (occurring in >30% of patients in either group) were infections, diarrhea, neutropenia, constipation, and fatigue. Infusion-related reactions also were most common in the daratumumab group (n=149; 40.9%).
Common grade 3/4 AEs included:
- neutropenia (50.0% in the daratumumab group and 35.3% in the control group)
- anemia (11.8% and 19.7%)
- lymphopenia (15.1% and 10.7%)
- pneumonia (13.7% and 7.9%)
- leukopenia (11.0% and 4.9%)
After a median follow-up of 28 months (range = 0-41.4 months), the 30-month progression-free survival (PFS) rate was 70.6% in the daratumumab group and 55.6% in the control group. This translated to a 44% reduction in the risk of disease progression or death with daratumumab (hazard ratio [HR] = 0.56; 95% CI 0.43-0.73; p<0.001). The median PFS was not reached with daratumumab, compared with 31.9 months in the control group (ranges not provided).
Prespecified subgroup analyses confirmed the benefits with daratumumab across all subgroups, except for patients who had hepatic impairment at baseline. The authors highlighted the PFS benefit seen among patients older than 75 years (HR=0.63; 95% CI 0.44-0.92; p value not provided).
Daratumumab also was associated with higher overall and complete response rates than Rd alone: 92.9% versus 81.3% and 47.6% versus 24.9% (p<0.001 for both comparisons; TABLE). The percentage of patients who achieved measurable residual disease negativity (to a threshold of 1×10-5 cells) was more than three times higher in the daratumumab group than the control group, the authors added.
“We anticipate that responses in individual patients, including negative status for [measurable] residual disease, will deepen over time, as has been observed with other daratumumab-containing regimens,” they added.
Taken together, “these findings can be added to those from a growing list of trials that support the use of daratumumab-based regimens across patient populations with MM,” the researchers concluded.
As a potential limitation of this analysis, the researchers noted that daratumumab-treated patients had a longer treatment duration and received less lenalidomide than the control group, “possibly owing to a higher incidence of AEs that led to dose discontinuations or dose modifications in this group,” which could have potentially affected results from the efficacy analysis.
The authors report relationships with Janssen, which sponsored the trial.
Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380:2104-15.