Updated results from MM-003 clinical trial: Health-related Quality of Life

The MM-003 trial compared pomalidomide treatment on a background of either low- or high- dose dexamethasone (POM+LoDEX or POM+HiDEX), for the treatment of relapsed and refractory Multiple Myeloma (RRMM) patients, that did not respond to their last line of treatment. The success of POM+LoDEX in this trial saw pomalidomide licensed for use in patients that have received at least two prior regimens, including lenalidomide and bortezomib. In a Letter to the Editor of Haematologica (the Journal for the European Hematology Association, EHA) K.W. Song and colleagues report an extended analysis of the MM-003 trial, in which they assessed health-related quality of life (HrQoL) and showed a significant benefit for the POM+LoDEX regimen. The design of the MM-003 trial is described in a previous MMHub article.

Key Findings:

• All patients (pts) were included, except those progressing on HiDEX that received POM in a companion trial (MM-003C)
• Three HRQoL instruments were used to assess non-progressing patients: European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-MY20, and EQ-5D
• Eight domains with EQ-5D utility index were used: five from EORTC QLQ-C30 (Global Health Status, Physical Functioning, Emotional Functioning, Fatigue, and Pain), two from EORTC QLQ-MY20 (Disease Symptoms, Side Effects of Treatment), and the EQ-5D Health Utility value (mapped to a scale of 1 = best health state and 0 = death using a time trade-off methodology)
• HRQoL questionnaires were completed on day 1 of each treatment cycle, and at discontinuation
• HRQoL scores were calculated from baseline through to cycle (C) 10 in the cross-sectional analyses; later cycles were limited by patients number, so all ITT pts with ≥1 HRQoL measurement were included in the analyses
• Cross-sectional descriptive and comparative analyses used domain scores analyzed as continuous variables
• Longitudinal analyses used a ‘repeated measure mixed effects model’ to estimate treatment effect on HRQoL over time and between treatment arms
• 433 pts were included in the HRQoL analysis (POM+LoDEX n=289; POM+HiDEX n=144)
• Median age = 64
• Prior treatment: >94% had received > 2 prior therapies; 82% were refractory to LEN and BORT
• Median follow-up = 10 months
• Data available at C10 POM+LoDEX vs POM+ HiDEX:                                                                         EORTC QLQ-C30 and QLQ-MY20 = 17.6% vs 5.5%                                                                         EQ-5D = 17.3% vs 4.8%
• Compliance rates up to C10 = ≥77.8%, although patient numbers dropped due to discontinuation and was higher in the HiDEX group

Results:

• Cross-sectional analysis: mean score improved significantly from baseline (P<0.05, paired t-test) in the POM+LoDEX arm for the Health Utility domain, and deteriorated significantly from baseline for Side Effects of Treatment
• In the HiDEX arm, no domains showed improvement; 5 showed deterioration from baseline: Physical Functioning, Health Utility, Fatigue, Disease Symptoms, and Side Effects of Treatment
• Between treatment groups, analysis favored POM+LoDEX in 5/8 domains: Physical Functioning, Emotional Functioning, Health Utility, Fatigue, and Side Effects of Treatment) at specific treatment cycles (P<0.05, unpaired t-test)
• Trends (P<0.1, unpaired t-test) also favored POM+LoDEX at specific time points for the Health Utility, Fatigue, and Disease Symptoms domains
• HiDEX treatment was inferior to POM+LoDEX across all domains
• Subgroup analyses in patients > 75 years or ≤75 years were consistent with overall findings
• Longitudinal analyses revealed significant (P<0.05) overall treatment differences between POM+LoDEX and HiDEX in all clinically relevant domains (except Disease Symptoms): Global Health Status (P=0.0451), Physical Functioning (P<0.0001), Emotional Functioning (P=0.0003), Health Utility (P=0.005), Fatigue (P=0.0008), Pain (P=0.0049), and Side Effects of Treatment (P=0.0253)
• Comparisons of adjusted means of score differences from baseline between treatment arms at each cycle confirmed superiority of POM+LoDEX in these seven domains

Following the success of the MM-003 clinical trial and improved clinical outcome with POM+LoDEX, this has become the standard of care treatment for relapsing patients who have previously received lenalidomide and bortezomib. This study concludes that POM+LoDEX leads to significant HRQoL improvements over time, often compromised in this patient set at this stage of their treatment journey, but an important factor nonetheless.