Prospective longitudinal study on quality of life in relapsed/refractory multiple myeloma patients receiving second- or third-line lenalidomide or bortezomib treatment

Treatment advances for multiple myeloma (MM) that have prolonged survival emphasise the importance of measuring patients’ health-related quality of life (HRQoL) in clinical studies.

HRQoL/functioning and symptoms of patients with relapsed/refractory MM (RRMM) receiving second- or third-line lenalidomide or bortezomib treatment were measured in a prospective European

multicentre, observational study at different time points. At baseline, patients in the lenalidomide cohort were frailer than in the bortezomib cohort with more rapid disease progression at

study entry (more patients with Eastern Cooperative Oncology Group performance status >2, shorter time from diagnosis, more chronic heart failure, higher serum creatinine levels, more

patients with dialysis required). About 40% of the patients receiving lenalidomide discontinued the study in 1 g/dl immunoglobulin G M-protein or >0.5 g/dl immunoglobulin A) and, where

applicable, urine light-chain excretion of ⩾200 mg/24 h + presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (that is, magnetic

resonance imaging, computed tomographic scan) or a quantifiable plasma cell infiltration of the bone marrow as determined by bone marrow biopsy. Patients who were planned to receive a

stem-cell transplant as part of the second-line treatment for MM and patients who were treated with a cytotoxic drug in combination with lenalidomide or bortezomib were excluded from the

study.

This study was conducted in compliance with the Declaration of Helsinki and all current national regulations. In accordance to local requirements, the study protocol was reviewed and

approved by the Independent Ethics Committee prior to the inclusion of patients into the study. All patients gave written informed consent prior to their inclusion.

This was a European, prospective, multicentre, observational, longitudinal study conducted in six countries (Belgium, France, Germany, Ireland, Italy and United Kingdom). Patients were

identified by their physician either through a prescreening and/or during the course of routine patient visits. Recruited patients were followed up for a maximum of 6 months. Physicians were

asked to specify the reason for any patients not completing the study: disease progression, discontinuation of treatment, or any other reasons, including death, withdrawn consent or lost to

follow-up.

Socio-demographic and clinical data were collected at baseline by the recruiting physicians. HRQoL was assessed using patient-completed questionnaires at baseline, 3 months and 6 months

following treatment initiation and/or at study discontinuation.

HRQoL was assessed using three questionnaires, the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Core (QLQ-C30),20, 21 QLQ-Multiple Myeloma (QLQ-MY20)22,

23 and QLQ-Chemotherapy-Induced Peripheral Neuropathy (QLQ-CIPN20)24 instruments. The QLQ-C30 includes 30 items distributed across six Functional domains (Cognitive, Emotional, Physical,

Role and social functioning, Global health status/QoL) and nine Symptom domains (Appetite loss, Constipation, Diarrhoea, Dyspnoea, Fatigue, Financial difficulties, Nausea and vomiting, Pain,

Insomnia). The QLQ-MY20 includes 20 items distributed across two Functional domains (Body image, Future perspective) and two Symptom domains (Disease symptoms, Side effects of treatment).

The QLQ-CIPN20 includes 20 items distributed across three symptom domains (Autonomic scale, Motor scale, Sensory scale). For all questionnaires, all items were answered on a four-point

Likert scale ranging from ‘not at all’ to ‘very much’, except items 29 and 30 of QLQ-C30 that are answered on a seven-point Likert scale ranging from ‘very poor’ to ‘excellent’. Scores were

converted to a range from 0 to 100; for Functional domains, higher scores indicate better functioning; for Symptom domains, higher scores indicate greater symptom.

Descriptive statistics were applied to describe the population, the individual components of the EORTC questionnaire and the change in EORTC questionnaire scores from baseline to month 3,

month 6 or study discontinuation. Changes in EORTC scores were calculated only for patients who were able to complete the questionnaires at both baseline and the time point of interest.

Minimal important difference (MID), defined as the smallest change in a quality of life score considered important to patients, was estimated within the study to provide support for the

interpretation of changes in scores.25 MID was calculated as 0.5 × SDbas, with SDbas the s.d. of the score at baseline, for single-item domains, and as the s.e.m., defined as SDbas ×

(1−r)1/2 with r the Cronbach’s alpha reliability coefficient, for multi-item domains.26

Patients in the bortezomib cohort were described by standard- or low-dose treatment: bortezomib treatment was considered as standard dose if ⩾6 vials and as low dose if 2 was slightly higher

in the lenalidomide cohort (6.2%) vs the bortezomib cohort (3.1%). Time since MM diagnosis was longer by >1 year in the bortezomib cohort (3.9±3.0 years) compared with the lenalidomide

cohort (2.8±2.5 years); also the upper quartile of time from diagnosis in the bortezomib cohort was 4.9–20.5 years vs 3.4–12.4 years in the lenalidomide cohort (Table 1). The ad hoc

statistical analysis showed that age and time since diagnosis were significantly different across the two cohorts (P