A subgroup analysis of the phase 3 MAIA trial showed rapid, deep, and durable responses with daratumumab plus lenalidomide and dexamethasone vs standard therapy for newly diagnosed multiple myeloma across patient subgroups.
Daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) resulted in consistently deep and durable responses compared with Rd alone for patients with transplant-ineligible newly diagnosed multiple myeloma, regardless of renal function or cytogenetic risk, according to a subgroup analysis from the phase 3 MAIA trial (NCT02252172) that was presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.1
At the median follow-up of 56.2 months, the median time to a very good partial response (VGPR) or better in the intent-to-treat population was 3.8 months in the D-Rd group vs 9.4 months in the Rd group (HR, 2.08; 95% CI, 1.73-2.49; P <.0001).
Stratifying outcomes by renal function, those with baseline creatine clearance (CrCl) at or below 60 mL/min had median time to VGPR of 3.8 months with D-Rd vs 12.5 months with Rd (HR, 2.26; 95% CI, 1.69-3.02; P <.0001). In those with CrCl 60 mL/min or more, median time to VGPR was 3.8 months with DR-d vs 8.5 months with Rd (HR, 1.82; 95% CI, 1.45-2.28; P <.0001).
Those with high cytogenic risk status with a VGPR or better had a median time to response of 4.7 months with DR-d vs 14.1 months with Rd (HR, 2.50; 95% CI, 1.44-4.36; P = .0008). Those with standard-risk status had a median time to VGPR or better of 3.8 months in the D-Rd group vs 9.3 months in the Rd group (HR, 1.96; 95% CI, 1.59-2.40; P <.0001).
The MAIA trial was designed to compare D-Rd vs Rd alone for patients with transplant-ineligible newly diagnosed multiple myeloma. Investigators found that the D-Rd regimen resulted in improved progression-free survival (PFS) as well as depth and duration of response. Patients were given 25 mg of oral lenalidomide on days 1 to 21; 40 mg or oral dexamethasone once a week; and 16 mg/kg of intravenous daratumumab once weekly for cycles 1 and 2, every 2 weeks for cycles 3 to 6, and every 4 weeks following.2
For the current analysis, patients were divided into subgroups based on renal impairment, at CrCl 60 mL/min or less, and cytogenetic risk, with deletion 17p (del17[p]) or t(14;16) abnormality denoting high-risk status. The primary end point was PFS with secondary end points of time to response and duration of response. Investigators also measured patient-reported outcomes (PROs) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item.
In the subgroup, a total of 368 patients were randomized to the D-Rd group and 369 in the Rd group. Baseline CrCl above 60 mL/min was reported for 56.0% and 61.5% of the D-Rd and Rd groups, respectively. Standard cytogenetic risk was noted for 85.0% of the DR-d group and 86.4% of the Rd group.
Median time to complete response (CR) or better in the overall population was 20.8 months in the D-Rd group vs 47.9 months in the Rd group (HR, 1.72; 95% CI, 1.36-2.18; P <.0001). The median time to a CR or better for those with CrCl greater than 60 mL/min was 17.6 months for the D-Rd group vs 43.8 months for the Rd group (HR, 1.80; 95% CI, 1.34-2.41; P <.0001); corresponding medians for those with CrCl of 60 mL/min or less was 23.3 months vs 54.6 months (HR, 1.58; 95% CI, 1.07-2.23; P = .0197). Those with the standard cytogenetic risk status had a median time to CR of 20.8 months in the D-Rd group vs 42.6 months in the Rd group (HR, 1.69; 95% CI, 1.29-2.21; P <.0001). Those with high-risk disease had a median time to CR of 15.7 months vs 47.9 months with DR-d and Rd, respectively (HR, 1.74; 95% CI, 0.83-3.63; P = .1372).
At 48 months, the estimated event-free survival (EFS) rate for those with a complete response was 81.8% in the D-Rd group vs 57.8% in the Rd group (HR, 0.38; 95% CI, 0.23-0.65; P = .0002).
Duration of CR or better was improved in the D-Rd group compared with the Rd group in patients with CrCl greater than 60 mL/min (HR, 0.41; 95% CI, 0.22-0.77; P = .0043), CrCl 60 mL/min or less (HR, 0.45; 95% CI, 0.20-1.04; P = .0551), standard cytogenic risk status (HR, 0.42; 95% CI, 0.24-0.73; P = .0015), and high-risk status (HR, 0.32; 95% CI, 0.09-1.16; P = .0694). The estimated 48-month EFS rates for DR-d vs RD were 82.2% vs 55.3%, respectively, for those with CrCl greater than 60 mL/min; 81.0% vs 61.5% for CrCl 60 mL/min or less; 80.0% vs 55.1%, with standard-risk cytogenetics; and 74.7% vs not estimable for high-risk features.
In the overall study population, improvement in the duration of partial response or better was observed in the D-Rd group vs the Rd group (HR, 0.50; 95% CI, 0.39-0.64; P <.0001). By subgroups, the response was similar in those with renal function of CrCl greater than 60 mL/min (HR, 0.50; 95% CI, 0.36-0.70; P <.0001), CrCl 60 mL/min or less (HR, 0.50; 95% CI, 0.34-0.74; P = .0003), cytogenic standard risk status (HR, 0.43; 95% CI, 0.32-0.57; P <.0001), and high risk status (HR, 0.65; 95% CI, 0.35-1.19; P = .1560). Additionally, the 48-month EFS rates for each subgroup treated with D-Rd vs Rd was 69.8% vs 48.9%, respectively, for CrCl greater than 60 mL/min; 67.2% vs 44.4% for CrCl 60 mL/min or less; 72.3% vs 45.7% for standard cytogenic risk status; and 48.8% vs 29.9% for high-risk status.
PROs showed a reduction in patient symptom scores for the D-Rd group compared with the Rd group during cycle 6, day 1 for those with renal impairment (least squares (LS) mean change from baseline, –14.9 vs –7.0, respectively; P = .0241). Improvement in pain scores was also observed for patients treated in the D-Rd group across most time points, and this was consistent across cytogenetic risk group.
At cycle 24, day 1, patients in the D-Rd group had a reduction in fatigue symptom scores compared with the Rd group (LS mean change from baseline, –2.9 vs 8.1, respectively; P = .0018). Similar results were observed at cycle 30, day 1 of (–3.7 vs 4.4; P = .0258) and cycle 36, day 1 (–2.6 vs 6.5; P = .0183). Additionally, investigators noticed a reduction in nausea and vomiting scores with DR-d vs RD at cycle 36, day 1 ( LS mean change from baseline, –3.7 vs 3.3; P = .0035).