Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression: a prospective, open-label, multicenter, randomized, phase 3 study

Abstract

Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after three and nine induction cycles and six and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in HRQoL reporting. Patients reported clinically relevant improvement in global quality of life (QoL), future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size. In general, improvement occurred after 6-12 months of maintenance only and was independent of the World Health Organisation performance at baseline. Patients treated with MPR-R reported clinically relevant worsening of diarrhea, and patients treated with MPT-T reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least three months reported clinically meaningful improvement in global QoL and role functioning at six months, remaining stable thereafter. There were no clinically meaningful deteriorations, but patients on thalidomide reported clinically relevant worsening in neuropathy. In general, HRQoL improves both during induction and maintenance therapy with immunomodulatory drugs. The side effect profile of treatment did not negatively affect global QoL, but it was, however, clinically relevant for the patients. (Clinicaltrials.gov identifier: NTR1630).

Figure 1.

Consort diagram. Consort diagram of the number of patients participating in the health-related quality of life (HRQoL) study, the number of answered questionnaires and the number of patients off protocol and reason for treatment discontinuation.

Figure 2.

Responders. The percentage of patients reaching a clinically relevant change in health-related quality of life (HRQoL), e.g. reaching the minimal important difference (MID) threshold for within group change during the induction phase (T2) and induction and maintenance phase together (T4). A significant difference between the arms with respect to the percentage of patients improving or deteriorating by more than the MID was observed for diarrhoea and peripheral neuropathy at T2 and for peripheral neuropathy at T4.

Figure 3.

Health-related quality of life change over time. Estimated change in health-related quality of life (HRQoL) score from baseline with corresponding 95% confidence intervals (CI) and P-values for the five scales with a statistically significant difference in change over time between treatment arms. Time points with clinically meaningful difference between arms (minimal important difference [MID] >5 points) are marked with *. The dotted horizontal line represents the calculated threshold for minimal important difference, the black for melphalan-prednisone-thalidomide induction and thalidomide maintenance therapy (MPT-T) and the blue for the melphalan-prednisone-lenalidomide induction and lenalidomide maintenance therapy (MPR-R) treatment. The green arrows indicate the direction of improvement in functional scales or reduction in symptom scales. The red arrows indicate the direction of deterioration in functional scales or worsening of symptom scales.

Figure 4.

Effect modification of global quality of life by World Health Organisation status. Mean global quality of life (QoL) course over time with corresponding 95% confidence intervals (CI) for each time point for (A) melphalan-prednisone-thalidomide induction and thalidomide maintenance therapy (MPT-T) and (B) patients treated with melphalan-prednisone-lenalidomide induction and lenalidomide maintenance therapy (MPR-R), differentiated by baseline World health organisation (WHO) performance status 0 versus 1 versus 2/3. The black curve represents patients with baseline WHO status 0, the blue curve the patients with WHO status 1 and the pink curve the patients with WHO status 2/3. The green arrows indicate the direction of improvement in functional scales and reduction in symptom scales.

Figure 5.

Patient- versus investigator-reported peripheral neuropathy. Patient-reported peripheral neuropathy compared to investigator-reported peripheral neuropaty assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The surface of the circles reflects the absolute number of patients plus investigators.