The Phase 3 MAIA study's updated analyses reported progression-free survival, minimal residual disease negativity, overall response and overall survival across patient types, regardless of age or cytogenetic risk.

These findings were presented in oral and poster presentations at the American Society of Hematology (ASH) 2022 Annual Meeting, and strengthened previous data from the MAIA study across clinically relevant study endpoints and patient populations.

“Initial data from the MAIA study were instrumental in establishing the D-Rd regimen as a standard of care for the treatment of patients with newly diagnosed, transplant-ineligible multiple myeloma,” said study author, Shaji Kumar, M.D., Consultant, Division of Hematology, Department of Internal Medicine, Mayo Clinic. “These updated findings continue to reinforce the overall survival benefit with the D-Rd regimen and provide important insights across key patient populations at varying ages and levels of cytogenetic risk.”

An updated efficacy analysis from the MAIA study reports data after 64.5 and 73.6 months of median follow-up on the primary study endpoint, PFS, and the secondary endpoints of MRD negativity, ORR, and OS (Abstract #4559). Additional new post hoc efficacy analyses report on critical subgroups, including by age (Abstract #4553) and by cytogenetic risk factors, including Gain(1q21) and Amp(1q21) (Abstract #3245).

“Daratumumab-based combination regimens are foundational in the treatment of newly diagnosed multiple myeloma, and the data presented at ASH provide further insight into the treatment of transplant-ineligible patients with the D-Rd regimen in the frontline setting,” said Mark Wildgust, Ph.D., Vice President, Global Medical Affairs, Janssen Research & Development, LLC. “Building on Janssen’s deep legacy in the treatment of multiple myeloma, we remain committed to evaluating the full potential of daratumumab in combination with lenalidomide and dexamethasone to meet the unique needs of various patient populations.”

The median age of the 737 patients enrolled in the MAIA trial was 73 (range: 45 to 90) years, with 44 percent of participants over the age of 75 years. Findings from the post-hoc subgroup analysis were consistent with previously reported data from the MAIA study on age and showed D-Rd improved OS, PFS, MRD-negativity, and ORR compared to Rd alone in all three age groups examined, including patients under 70 years of age, between 70 and 75 years of age, and under the age of 75.

In patients under 75 years (D-Rd, n=208; Rd, n=208) who were treated with D-Rd, median PFS was not reached vs. 37.5 months in the Rd arm [hazard ratio (HR): 0.52, 95 percent confidence interval (CI), 0.39-0.68]. MRD-negativity was 36.1 percent vs. 12.0 percent [odds ratio (OR), 4.13; 95 percent CI, 2.49-6.84]. The ORR was 95.2 percent vs. 81.7 percent.

In patients under 70 years of age (D-Rd, n=78; Rd, n=77) who were treated with D-Rd, median PFS was not reached vs. 39.2 months in the Rd arm (HR, 0.35; 95 percent CI, 0.21-0.56). MRD-negativity was 35.9 percent vs. 11.7 percent (OR, 4.23; 95 percent CI, 1.84-9.75). The ORR was 93.6 percent vs. 80.5 percent.

Lastly, in patients ages 70 through 75 (D-Rd, n=130; Rd, n=131), who were treated with D-Rd, median PFS was reached at 61.9 months vs. 37.5 months in the Rd arm (HR, 0.64; 95 percent CI, 0.45-0.89; P = 0.0079). MRD-negativity was 36.2 percent vs. 12.2 percent (OR, 4.07; 95 percent CI, 2.16-7.67). The ORR was 96.2 percent vs. 82.4 percent.

A second analysis in key clinical subgroups (Abstract #3245) reported increased PFS, MRD-negativity and ORR following treatment with D-Rd in patients 75 or older, with International Staging System (ISS) stage III disease, with high cytogenetic risk, with renal insufficiency, and with extramedullary plasmacytomas. Key highlights include:

Patients with high cytogenetic risk, defined as having one or more of the abnormalities t[4;14], t[14;16] or del17p, had a median PFS of 45.3 months following treatment with D-Rd vs. 29.6 months with Rd alone (HR, 0.57; 95 percent CI, 0.34-0.96) (D-Rd, n=48; Rd, n=44).  MRD-negativity was 25.0 percent compared to 2.3 percent (OR, 14.33, 95 percent CI, 1.78-115.59) and the ORR was 91.7 percent vs. 75 percent (OR, 3.67, 95 percent CI, 1.07-12.55).

Patients with Gain(1q21) or Amp(1q21) had a median PFS of 53.2 months following treatment with D-Rd vs. 32.3 months with Rd alone (HR, 0.63; 95 percent CI, 0.46-0.88) (D-Rd, n=127; Rd, n=120). MRD-negativity was 33.1 percent compared to 11.7 percent (OR, 3.74, 95 percent CI, 1.92-7.30) and the ORR was 95.3 percent vs. 85 percent (OR, 3.56, 95 percent CI,1.36-9.30).

The rates of Grade 3/4 and serious treatment-emergent adverse events (TEAEs) were similar in both treatment groups for patients 75 years of age or older, with a lower rate of discontinuation due to TEAEs for patients treated with D-Rd compared to Rd alone.

In a fourth analysis presented from the MAIA study, patient-reported outcomes (PRO) data were highlighted in an oral presentation, and showed sustained improvements in HRQoL and physical functioning among a subgroup of frail patients treated with D-Rd compared to Rd, with a notable reduction in pain throughout the duration of treatment (Abstract #472). A higher percentage of patients continued treatment with D-Rd, compared to those receiving Rd alone.

Source: Janssen