Meta-Analytic Summary of the Burden of Pain and Fatigue in Multiple Myeloma

Aims:

Multiple myeloma (MM) is a hematologic malignancy of plasma cells. Bone disease is a characteristic symptom of MM, and pain is one of its most distressing features. Anemia is also a common symptom and is manifested as fatigue and tiredness among MM patients. We conducted a systematic review and meta-analysis of the EORTC QLQ-C30 pain and fatigue scales in two clinical MM populations (one with newly-diagnosed MM and a second undergoing medical management with re-emergent or advanced myeloma) to more precisely quantify the burden of pain and fatigue in MM.

Methods:

Studies assessing pain and fatigue in MM were identified through a search of specific terms in the medical-subject headings and keywords in PubMed. Inclusion criteria were English-language studies published between January 1, 1996, and July 1, 2014; diagnosis of MM; and availability of data on pain and/or fatigue as measured by the EORTC QLQ-C30. Full-text articles from germane abstracts were retrieved for eligibility assessment, and 27 articles were selected for inclusion in the analysis. Two groups of peer-reviewed articles were created: one consisting of publications that focused on newly-diagnosed MM and the other consisting of articles involving MM patients with advanced conditions, including those who had a disease recurrence or were receiving autologous bone marrow transplantation.

The mean values and standard deviations (SDs) were recorded across all publications irrespective of sex, age, and stage of illness. Of the 27 studies, 17 did not report standard error (SE) or SD values associated with EORTC QLQ-C30 pain and fatigue scales. These missing values were estimated using the overall average of SDs for that scale observed across all studies within the publication group (either newly-diagnosed or recurrent/advanced disease). A sensitivity analysis was conducted to compare the pooled mean and SEs associated with results obtained with and without the SD imputation procedure.

The means and SDs from the two sets of publications were entered into Comprehensive Meta-analysis^™ with both scales (pain or fatigue) and existing or imputed SDs as grouping variables. The summary means and confidence intervals for each scale by clinical group were computed by weighting the individual studies by sample size and were statistically summarized based on a fixed-effect model.

Results:

The EORTC QLQ-C30 fatigue and pain scales range from 0-100 with higher scores indicating greater symptoms (i.e., more fatigue and pain). The overall mean across the 27 publications was 47.1 for fatigue and 48.2 for pain for MM patients compared to scores of 25.0 and 16.9 for a general population. The results of the sensitivity analysis indicated that estimation of the SDs for those studies missing the statistic did not have a significant effect on the summary mean estimate. In most cases, the inclusion of additional means with estimated SDs reduced the summary SE estimate associated with the summary mean. Overall, the scores for fatigue and pain across research articles involving newly-diagnosed patients (fatigue=48.5 and pain=49.1) were statistically higher (indicating worse pain and fatigue) than among patients who were recurrent or receiving more aggressive treatments (fatigue=39.9 and pain=38.7).

Conclusions:

The burden of pain and fatigue in MM is substantial and is different between newly-diagnosed and more advanced MM patients. Pain and fatigue can be easily quantified using standardized health-related quality of life instruments. Pivotal clinical trials in MM need to assess the impact of novel treatments on pain and fatigue.