Factors that influence health-related quality of life in newly diagnosed patients with multiple myeloma aged ≥ 65 years treated with melphalan, prednisone and lenalidomide followed by lenalidomide maintenance: results of a randomized trial

Figures & data

Figure 1. (A) Design overview of trial MM-015. (B) Flow of participants in trial MM-015. ISS, International Staging System; MP, melphalan, prednisone and placebo followed by maintenance therapy with placebo; MPR, melphalan, prednisone and lenalidomide followed by maintenance therapy with placebo; MPR-R, melphalan, prednisone and lenalidomide followed by maintenance therapy with lenalidomide; PBO, placebo; po, by mouth.

Table I. Overview of determinants of HRQoL following baseline assessment in patients treated with MPR-R, MPR or MP* (statistical significance: p < 0.05).

	Global QoL (n = 394), MID + 7	Physical Functioning (n = 404), MID + 9	Fatigue (n = 398), MID − 10	Pain (n = 399), MID − 12	Disease Symptoms (n = 393), MID − 10	Side Effects of Treatment (n = 391), MID − 6
Cycle 4 vs. cycle 16	− 5.24 (p < 0.001)	− 3.74 (p = 0.001)	+ 4.54 (p < 0.001)	NS	NS	+ 2.38 (p = 0.004)
Cycle 7 vs. cycle 16	− 3.35 (p = 0.015)	NS	NS	NS	NS	+ 2.32 (p = 0.005)
Cycle 10 vs. cycle 16	NS	NS	+ 3.19 (p = 0.018)	NS	NS	+ 1.70 (p = 0.038)
Cycle 13 vs. cycle 16	NS	NS	NS	NS	NS	NS
MPR-R vs. MP	NS	NS	NS	NS	NS	NS
MPR vs. MP	NS	NS	NS	NS	NS	NS
Female vs. male	− 4.03 (p = 0.006)	− 3.61 (p = 0.022)	NS	+ 4.60 (p = 0.037)	+ 3.62 (p = 0.017)	+ 3.62 (p < 0.001)
Age, years	− 0.42 (p = 0.006)	− 0.67 (p < 0.001)	+ 0.39 (p = 0.032)	NS	NS	+ 0.27 (p = 0.010)
Baseline HRQoL score	+ 0.34 (p < 0.001)	+ 0.47 (p < 0.001)	+ 0.38 (p < 0.001)	+ 0.32 (p < 0.001)	+ 0.45 (p < 0.001)	+ 0.50 (p < 0.001)
PR vs. SD	NS	NS	NS	NS	NS	− 1.42 (p = 0.038)
VGPR or better vs. SD	+ 9.80 (p = 0.007)	+ 8.47 (p = 0.008)	− 8.58 (p = 0.021)	− 11.01 (p = 0.020)	− 6.97 (p = 0.028)	− 5.28 (p = 0.018)
Progressive disease	− 8.38 (p < 0.001)	− 7.45 (p < 0.001)	+ 7.22 (p < 0.001)	+ 8.33 (p < 0.020)	+ 3.97 (p = 0.007)	NS
Discontinued	− 5.41 (p = 0.015)	− 3.82 (p = 0.046)	NS	NS	NS	NS
Neutropenia grade 3–4	NS	NS	NS	NS	NS	NS
Anemia grade 3–4	− 11.23 (p = 0.004)	− 19.02 (p < 0.001)	+ 20.27 (p < 0.001)	NS	+ 7.72 (p = 0.020)	+ 7.58 (p = 0.001)

HRQoL, health-related quality of life; MID, minimal important difference; MP, melphalan, prednisone and placebo followed by maintenance therapy with placebo; MPR, melphalan, prednisone and lenalidomide followed by placebo maintenance therapy; MPR-R, melphalan, prednisone and lenalidomide followed by maintenance therapy with lenalidomide; NS, not significant; PR, partial response; SD, stable disease; VGPR, very good PR.

*Data show HRQoL score point changes (i.e. improvement or deterioration): increases in HRQoL score indicate improvements for Global QoL and Physical Functioning; decreases in HRQoL score indicate improvements for Fatigue, Pain, Disease Symptoms and Side Effects of Treatment. Italicized bold text means MID has been reached.

Table II. Overview of determinants of HRQoL following baseline assessment in patients aged 65–75 years treated with MPR-R, MPR or MP* (statistical significance: p < 0.05).

	Global QoL (n = 308), MID + 7	Physical Functioning (n = 316), MID + 9	Fatigue (n = 311), MID − 10	Pain (n = 312), MID − 12	Disease Symptoms (n = 307), MID − 10	Side Effects of Treatment (n = 306), MID − 6
Cycle 4 vs. cycle 16	− 5.28 (p < 0.001)	− 4.85 (p < 0.001)	+ 5.21 (p < 0.001)	NS	NS	+ 2.42 (p = 0.005)
Cycle 7 vs. cycle 16	− 3.20 (p = 0.031)	− 2.38 (p = 0.047)	+ 3.52 (p = 0.013)	NS	NS	+ 2.38 (p = 0.005)
Cycle 10 vs. cycle 16	NS	NS	+ 3.18 (p = 0.024)	NS	NS	NS
Cycle 13 vs. cycle 16	NS	NS	NS	NS	NS	NS
MPR-R vs. MP	NS	NS	NS	NS	NS	NS
MPR vs. MP	NS	NS	NS	NS	− 4.91 (p = 0.017)	NS
Female vs. male	− 5.46 (p < 0.001)	− 4.84 (p = 0.006)	+ 5.43 (p = 0.007)	+ 5.84 (p = 0.014)	+ 5.02 (p = 0.003)	+ 4.28 (p < 0.001)
Age, years	NS	− 0.80 (p = 0.004)	NS	NS	NS	NS
Baseline HRQoL score	+ 0.34 (p < 0.001)	+ 0.45 (p < 0.001)	+ 0.37 (p < 0.001)	+ 0.33 (p < 0.001)	+ 0.44 (p < 0.001)	+ 0.50 (p < 0.001)
PR vs. SD	NS	NS	NS	NS	NS	− 1.50 (p = 0.040)
VGPR or better vs. SD	+ 12.19 (p = 0.003)	+ 7.92 (p = 0.029)	− 11.29 (p = 0.008)	− 14.23 (p = 0.009)	− 9.63 (p = 0.008)	− 6.49 (p = 0.009)
Progressive disease	− 8.62 (p < 0.001)	− 7.91 (p < 0.001)	+ 7.63 (p < 0.001)	+ 8.45 (p < 0.001)	+ 4.46 (p = 0.004)	+ 2.41 (p = 0.025)
Discontinued	− 6.45 (p = 0.012)	− 6.02 (p = 0.007)	+ 5.34 (p = 0.038)	NS	NS	NS
Neutropenia grade 3–4	NS	NS	NS	NS	NS	NS
Anemia grade 3–4	NS	− 14.79 (p < 0.001)	+ 19.21 (p < 0.001)	NS	NS	NS

HRQoL, health-related quality of life; MID, minimal important difference; MP, melphalan, prednisone and placebo followed by maintenance therapy with placebo; MPR, melphalan, prednisone and lenalidomide followed by placebo maintenance therapy; MPR-R, melphalan, prednisone and lenalidomide followed by maintenance therapy with lenalidomide; NS, not significant; PR, partial response; SD, stable disease; VGPR, very good PR.

*Data show HRQoL score point changes (i.e. improvement or deterioration): increases in HRQoL score indicate improvements for Global QoL and Physical Functioning; decreases in HRQoL score indicate improvements for Fatigue, Pain, Disease Symptoms and Side Effects of Treatment. Italicized bold text means that MID has been reached.

Figure 2. Analysis outline of HRQoL assessment: comparison of during treatment versus end of treatment (PD or DC). Statistical significance was determined after applying a Bonferroni adjustment for multiple treatments. Italicized text means that the MID was achieved. DC, discontinuation (for any reason other than progressive disease); HRQoL, health-related quality of life; MID, minimal important difference; MP, melphalan, prednisone and placebo followed by maintenance therapy with placebo; MPR-R, melphalan, prednisone and lenalidomide followed by maintenance therapy with lenalidomide; PD, progressive disease.

Figure 3. Mean HRQoL scores during treatment versus end of treatment (PD) by treatment group. Mean differences in scores were added to the x-axis. Bold table entries were statistically significant after applying a Bonferonni adjustment for multiple treatments and/or were clinically meaningful. HRQoL, health-related quality of life; MID, minimal important difference; MP, melphalan, prednisone and placebo followed by maintenance therapy with placebo; MPR-R, melphalan, prednisone and lenalidomide followed by maintenance therapy with lenalidomide; PD, progressive disease.

Figure 4. Mean HRQoL scores for baseline, best during treatment and at PD according to treatment group. Increases in HRQoL score indicate improvements/better HRQoL for Global QoL and Physical Functioning; decreases in HRQoL score indicate improvements/better HRQoL for Fatigue, Pain, Disease Symptoms and Side Effects of Treatment. Symbols indicate statistical significance based on Bonferroni-adjusted p-values for comparisons of multiple treatments of best score versus baseline score (*) and best score versus PD score (+) within treatment group. HRQoL, health-related quality of life; MP, melphalan, prednisone and placebo followed by maintenance therapy with placebo; MPR, melphalan, prednisone and lenalidomide followed by maintenance therapy with placebo; MPR-R, melphalan, prednisone and lenalidomide followed by maintenance therapy with lenalidomide; PD, progressive disease.