Combination therapy of daratumumab, lenalidomide, and dexamethasone (D-Rd) led to clinical response in frail patients with newly diagnosed multiple myeloma.
A team, led by Aurore Perrot, MD, PhD, Center Hospitalier Universitaire de Toulouse, Department of Hematology, evaluated patient-reported outcomes in frail patients in data presented at the 2022 annual meeting of the American Society of Hematology (ASH).
MAIA trial
In a previous analysis of the MAIA trial, researchers found that daratumumab, lenalidomide, and dexamethasone (D-Rd) improved progression-free survival (PFS) in non-transplant-eligible patients with multiple myeloma newly diagnosed (NDMM) versus Revlimid and dexamethasone (Rd).
This benefit continued through longer follow-up with a median of 56.2 months, showing overall survival benefit, deeper response and significant improvements in patient-reported outcomes.
The median age of patients was 73 years and 43.6% of the patient population was at least 75 years old.
The study also included a subgroup analysis of frailty with a median age of 77 years. Here, investigators found that D-Rd showed deeper responses and PFS benefit compared to Rd (not achieved [NR] versus 30.4 months; HR, 0.62; P = 0.003) in frail patients at a median follow-up of 36.4 months.
However, little is known about health-related quality of life outcomes in elderly and frail patients.
In the study, researchers randomized 737 patients to D-Rd or Rd until disease progression or unacceptable toxicity and assessed frailty using age, Charlson Comorbidity Index, and baseline score. Eastern Cooperative Oncology Group performance status.
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 30-item baseline questionnaire on the quality of life (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 researchers defined significant thresholds for improvement and worsening as a priori based on the published literature (change ≥ 10 points) and assessed the treatment effect by a mixed-effects model for repeated measures.
Subgroup analysis
Overall, there were patients in the fragile group (D-Rd, n=172; Rd, n=169,) with a median follow-up of 64.5 months. Patients in the fragile group treated with D-Rd reported greater improvements from baseline compared to the Rd-to-Rd group in EORTC QLQ-C30 Global Health Status (GHS) scores and physical functioning (mean change LS versus initially for D-Rd at Cyc 12, 12.7 versus Rd, 9.8) at several points.
Additionally, 39% of D-Rd-treated patients remained on treatment with patient-reported outcome assessment at cycle 48, compared to 17% in the Rd group.
Additionally, patients treated with D-Rd showed particularly large reductions (≥20 point change) in pain symptoms over time and greater than those seen in patients treated with Rd.
Investigators observed significant changes from baseline in fatigue symptoms for either treatment group.
Results for emotional functioning, social functioning, and nausea and vomiting also numerically favored D-Rd at several time points.
Additionally, median time to first improvement was numerically shorter with D-Rd compared to Rd for SGH (D-Rd, 2.38 months vs. Rd, 4.67 months), physical functioning (2 .60 months versus 4.65 months), pain (2.07 months versus 2.83 months). months) and symptoms of fatigue (2.04 months versus 3.09 months).
Median time to first worsening was longest for physical functioning (D-Rd, 68.14 months versus 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 SGH (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 scales, including emotional, social, role, and symptom, including nausea and vomiting, numerically favored D-Rd vs Rd, with the exception of cognitive functioning. and fatigue.
“D-Rd demonstrates clinical benefit in all patients, including frail patients,” the authors wrote. “Additionally, frail patients treated with D-Rd reported long-lasting improvements in overall health (overall HRQoL) and physical functioning, with a notable reduction in pain over the course of treatment. Additionally, a higher percentage of frail patients continued on D-Rd vs. Rd. The D-Rd regimen is not only clinically effective, but also results in sustained HRQoL improvement for TIE frail patients with NDMM. »
The study, “Health-related quality of life in frail transplant-ineligible patients with newly diagnosed multiple myeloma treated with daratumumab, lenalidomide, and dexamethasone: subgroup analysis of the MAIA trial” , was published online by CASH 2022.
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