Daratumumab, Lenalidomide and Dexamethasone Clinically Beneficial for Frail Patients With Multiple Myeloma

Aurore Perrot, MD, PhD

A combination therapy of daratumumab, lenalidomide and dexamethasone (D-Rd) led to a clinical response for frail patients with newly diagnosed multiple myeloma.

A team, led by Aurore Perrot, MD, PhD, Centre Hospitalier Universitaire de Toulouse, Service d'Hématologie, assessed patient-reported outcomes in frail patients in data presented during the 2022 American Society of Hematology (ASH) Annual Meeting.

MAIA Trial

In a previous analysis of the MAIA trial, investigators found daratumumab, lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) compared to just Revlimid and dexamethasone (Rd).

This benefit continued throughout a longer follow-up with a median of 56.2 months, showing an overall survival benefit, deeper response, and meaningful improvements in patient-reported outcomes.

The median age of patients was 73 years and 43.6% of the patient population was aged at least 75 years.

The study also included a frailty subgroup analysis with a median age of 77 years. Here, the investigators found D-Rd showed deeper responses and PFS benefit comparted to Rd (not reached [NR] vs 30.4 months; HR, 0.62; P = 0.003) in frail patients at a median follow-up of 36.4 months.

However, there is little known about health-related quality of life outcomes in elderly, frail patients.

In the study, the investigators randomized 737 patients to D-Rd or Rd until disease progression or unacceptable toxicity and assessed frailty using age, Charlson Comorbidity Index, and baseline Eastern Cooperative Oncology Group performance status score.

They then categorized the patients into frail or non-frail subgroups and assessed patient-reported outcomes using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30).

Each participant completed the questionnaires at baseline, on day 1 of cycles 3, 6, 9, and 12 for year 1, and every 6 months until disease progression.

The investigators defined meaningful thresholds for improvement and worsening as a priori based on published literature (≥10-point change) and assessed treatment effect by a mixed-effects model for repeated measures.

Subgroup Analysis

Overall, there were patients in the frail group (D-Rd, n = 172; Rd, n = 169,) with a median follow-up of 64.5 months. Patients in the frail group treated with D-Rd reported greater improvements from baseline compared to the Rd group in Rd in EORTC QLQ-C30 Global Health Status (GHS) scores and physical functioning (LS mean change from baseline for D-Rd at Cyc 12, 12.7 vs Rd, 9.8) at several time points.

In addition, 39% of patients treated with D-Rd stayed on treatment with patient-reported outcome assessment at cycle 48 compared to 17% in the Rd group.

Additionally, patients treated with D-Rd had notably large reductions (≥20-point change) in pain symptoms over time and larger than that seen in patients treated with Rd.

The investigators did observe meaningful changes from baseline in fatigue symptoms for either treatment group.

The results for emotional functioning, social functioning, and nausea and vomiting also numerically favored D-Rd at several time points.

Moreover, the median time to first improvement was numerically shorter with D-Rd compared to Rd for GHS (D-Rd, 2.38 months vs Rd, 4.67 months), physical functioning (2.60 months vs 4.65 months), pain (2.07 months vs 2.83 months), and fatigue symptoms (2.04 months vs 3.09 months).

The median time to first worsening was longest for physical functioning (D-Rd, 68.14 month vs Rd, 39.62 months; HR, 0.66; 95%CI, 0.45–0.95; P = 0.023) and pain symptoms (D-Rd: NR vs Rd, 60.48 months; HR, 0.66; 95% CI, 0.44–1.00; P = 0.045), while the median time to first worsening was longer with D-Rd vs Rd for GHS (D-Rd: 29.31 months vs Rd: 21.62 months; HR, 0.91; 95% CI, 0.65–1.26).

Finally, the median time to first worsening for the other functional, including emotional, social, role and symptom, including nausea and vomiting, scales numerically favored D-Rd vs Rd, except cognitive functioning and fatigue.

“D-Rd demonstrates clinical benefit in all patients, including frail patients,” the authors wrote. “In addition, frail patients treated with D-Rd reported sustained improvements in global health (overall HRQoL) and physical functioning, with notable reduction in pain through the duration of therapy. Additionally, higher percentage of frail patients continued on D-Rd vs Rd. D-Rd regimen is not only clinically effective but also results in a sustained improvement in HRQoL for TIE frail pts with NDMM.”

The study, “Health-Related Quality of Life for Frail Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Daratumumab, Lenalidomide and Dexamethasone: Subgroup Analysis of MAIA Trial,” was published online by ASH 2022.