DRd Outperforms Rd in Newly Diagnosed Multiple Myeloma

DRd Outperforms Rd in Newly Diagnosed Multiple Myeloma

Findings from a subgroup analysis of the phase 2 MAIA trial (NCT02252172) demonstrated that daratumumab (Darzalex) plus lenalidomide (Revlimid) and dexamethasone (D-Rd) yielded superior responses over Rd alone in transplant-ineligible patients with newly diagnosed multiple myeloma–regardless of renal function or cytogenetic risk.¹

The findings, which were presented at the 2022 ASCO Annual Meeting, found that, at the median fol­low-up of 56.2 months, the median time to a very good partial response (VGPR) or better in the intention-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 D-Rd 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 D-Rd 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 Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item.¹

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 D-Rd 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 D-Rd 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 D-Rd 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 D-Rd vs RD at cycle 36, day 1 (LS mean change from baseline, –3.7 vs 3.3; P = .0035).

References

1. Facon T, Kumar S, Plesner T, et al. Time to response, duration of response, and patient-reported outcomes (PROs) with daratumumab (DARA) plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): Subgroup analysis of the phase 3 MAIA study. J Clin Oncol. 2022;40(suppl 16):8044. doi:10.1200/JCO.2022.40.16_suppl.8044
2. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596. doi:10.1016/S1470-2045(21)00466-6