Relapsed/refractory patients

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.

References
  1. Song KW. et al. Health-related quality of life from the MM-003 trial of pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed and/or refractory multiple myeloma. Haematologica. 2015 Feb;100(2):e63-7. DOI: 10.3324/haematol.2014.112557. Epub 2014 Nov 25.
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