Daratumumab Combo Shows Durable HRQOL Improvement in NDMM

Daratumumab plus lenalidomide/dexamethasone for multiple myeloma showed improved 5-year health-related quality of life vs lenalidomide/dexamethasone alone.

The addition of daratumumab (Darzalex) to lenalidomide (Revlimid) and dexamethasone (D-Rd) improved health-related quality of life (HRQOL) outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) vs lenalidomide and dexamethasone (Rd) alone, according to a post hoc analysis of the phase 3 MAIA trial (NCT02252172) published in the European Journal of Haematology.1

Results from the trial showed that clinically meaningful improvements in global health status (GHS) scores were observed in 54.6% of patients in the D-Rd arm (n = 368) at cycle 36 vs 39.5% in the Rd arm (n = 369; OR, 1.84; 95% CI, 1.16-2.91). At cycle 60, meaningful clinical improvements were observed in 52.6% and 50.0% of each respective arm (OR, 1.11; 95% CI, 0.56-2.20). Additionally, the median time to GHS worsening was 26.8 months with D-Rd vs 21.3 months with Rd (HR, 0.9; 95% CI, 0.7-1.1).

Additionally, GHS findings were similar for the frailty subgroups (OR, 1.75; 95% CI, 0.84-3.66); across age categories; and among patients with bone lesions (OR, 1.71; 95% CI, 1.01-2.88) compared with the intent-to-treat (ITT) population. A similar improvement in GHS score occurred between treatment arms for all subgroups.

Further data revealed that patients treated with D-Rd in the ITT population experienced an approximately 15-point improvement in pain scores, with improvements observed across most patient subgroups. Particularly for patients with bone lesions, an improvement of approximately 20 points in pain scores was observed. At cycle 36, 57.0% in the D-Rd group vs 48.3% in the Rd arm had clinically meaningful improvements in pain (OR, 1.42; 95% CI, 0.84-2.39). In the respective groups, the rates were 58.9% vs 42.1% at cycle 60 (OR, 1.97; 95% CI, 0.91-4.25).

Enhanced scores on the physical functioning and fatigue subscales were also observed in the D-Rd arm vs Rd alone. At cycle 36, the threshold for minimally important change in the physical functioning subscale was met in 42.5% vs 27.7% of the respective groups (OR, 1.93: 95% CI, 1.18-3.14); at cycle 60, it was met in 45.6% vs 23.9%, respectively (OR, 2.67; 95% CI, 1.23-5.77). At cycles 36 and 60, the threshold for minimally important change in the fatigue subscale was 45.4% with D-Rd vs 29.4% Rd alone (OR, 2.00; 95% CI, 1.24-3.23) and 45.6% vs 32.6% (OR, 1.73; 95% CI, 0.85-3.55), respectively.

“The current results extend the findings from the 1-year analysis of HRQOL in the ITT population and in subgroups according to age, ECOG [performance status], and depth of treatment response,” Aurore Perrot, MD, PhD, associate professor in hematology at the University of Toulouse, France, wrote in the publication with study coinvestigators.1 “The addition of the frail subgroup in this updated analysis is clinically relevant, as frailty status takes into account patient comorbidities and ECOG [performance status] in addition to age, providing more granularity on patient status, as patient fitness is not dictated by age alone.”

Patients with transplant-ineligible NDMM and an ECOG performance status score of 0 to 2 in the phase 3 MAIA study were randomly assigned 1:1 to receive D-Rd or Rd alone. Those enrolled were stratified by International Staging System (ISS) disease stage, geographic region, and age.

In both arms, patients received 40 mg of oral or intravenous dexamethasone once weekly, reduced to 20 mg for patients older than 75 years, and 35 mg of oral lenalidomide once daily for days 1 to 21 of 28-cycles, with dose adjustments permitted for renal insufficiency. In the investigational arm, patients received 16 mg/kg of intravenous daratumumab once weekly for 8 weeks, followed by every other week for 16 weeks, and every 4 weeks starting cycle 7. Treatment was received until disease progression or unacceptable toxicity.

Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer QOL questionnaire core 30 (EORTC QLQ-C30). This assessment comprises a GHS assessment, 5 functional scales, 3 symptom scales, and 6 single items, with patients completing assessments at baseline; on day 1 of cycles 3, 6, 9, and 12; and day 1 of every sixth subsequent cycle until treatment discontinuation. Scores were transformed to a scale of 0 to 100.

The primary end point of the study was progression-free survival.2 Secondary end points included complete response rate, very good partial response rate, minimal residual disease rate, overall response rate, overall survival, and safety.

References

1. Perrot A, Facon T, Plesner T, et al. Sustained improvement in health-related quality of life in transplant-ineligible newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone: MAIA final analysis of patient-reported outcomes. Eur J Haematol. Published online February 14, 2025. doi:10.1111/ejh.14392
2. Study comparing daratumumab, lenalidomide, and dexamethasone with lenalidomide and dexamethasone in participants with previously untreated multiple myeloma. ClinicalTrials.gov. Updated February 11, 2025. Accessed February 25, 2025. https://tinyurl.com/yujwznd4