Monthly theme | An introduction to patient reported outcomes (PROs) and quality of life (QoL) assessments in multiple myeloma 

Disparity between clinician- and patient-reported outcomes

It has been shown in MM that physicians can underestimate the symptom-burden of their patients and that there is a lack of correlation between symptomatic adverse events (AEs) reported by physicians, and symptoms reported by patients. For example, Lene Kongsgaard Nielsen and colleagues showed that patient-reported and clinician-reported AEs were poorly correlated when completing a series of three HRQoL questionnaires during treatment with clarithromycin, bortezomib, cyclophosphamide and dexamethasone. In fact, in this study the authors concluded there was “clear underreporting of toxicities by clinicians”.⁹

This is significant as the understanding of efficacy and safety of a treatment is based on adherence to a treatment regimen. If patients do not adhere to therapy in order to avoid unpleasant AEs, this impacts the study conclusions. Additionally, if conclusions are drawn based on restricted or limited data, this will not translate into the real-world setting.¹

Therefore, it is important to monitor the patient’s symptom burden and HRQoL, particularly in the outpatient setting, where oral therapies are increasingly utilized to promote patient independence. Using self-reported QoL measures may help identify treatment compliance issues, allowing earlier intervention.¹

Examples of studies on QoL in MM

In a study by Christina Ramsenthaler and colleagues, published in BMC Cancer in 2016, it was shown that patients with MM have a high symptom burden and low HRQoL in both early and advanced stages of disease. The mean number of symptoms per patient (N= 557) was 7.2 out of a potential 15, the most common of which were pain (72%), fatigue (88%) and breathlessness (61%). Patients with RRMM had the highest mean number of symptoms. Factors associated with high palliative care concerns were identified to be; a high symptom level, pain, anxiety, low physical function, a younger age, and advanced stage of disease. The authors of this study concluded that the identification of patients who require supportive care should be done using PROs and be complementary to traditional biomarker assessment.¹⁰

In July 2019, Professor Graham Jackson and colleagues, published the results of an analysis of productivity losses in patients with NDMM following ASCT in the European Journal of Haematology. The study analyzed patients prior to diagnosis and post-ASCT to evaluate the impact of transplant on productivity, employment and work. It subsequently analyzed whether maintenance therapy with lenalidomide could reduce this productivity loss, as lenalidomide maintenance has previously been shown to increase overall survival (OS), PFS and HRQoL.¹¹

• Patients (N= 115) were recruited from five European countries (UK, France, Germany, Italy and Spain, EU5) and asked to complete an online survey
• 76.5% of patients were economically active at diagnosis
• 39.1% were economically active post-ASCT
• Proportion of patients in full-time employment: 46% (at diagnosis) vs 17% (post-ASCT)
• Productivity loss was highest in patients aged 50–65 years compared to those < 50 years old
• Most productivity losses observed were due to patients retiring or not returning to work
• Estimated productivity loss per ASCT patient (over a 20-year period): €290,601
• Maintenance with lenalidomide reduced this loss by ~10%

This study evaluated patient-reported survey data. Patients prioritized a desire to lead an active life over the financial aspect of working, and 80% of overall productivity loss was contributed to an inability to return to work due to a lack of fitness to carry out routine tasks.¹¹

In summary, most patients highlighted that returning to work was a factor affecting their QoL, though unfortunately most are unable to, post-ASCT. Extending remission periods and encouraging engagement in a productive life can have a positive impact on the patient as well as the wider society.¹¹

Studies such as that by Graham Jackson and colleagues highlight the need to support patients with NDMM, post-ASCT, who wish to return to employment, as well as noting the impact of ASCT on productivity.

Conclusion

There are many different factors to consider when determining the appropriate treatment for a patient with MM. In addition to the current standard-of-care treatments authorized within each country, physicians must consider whether a clinical trial involving a novel therapy or new combination is suitable, and combine this with information about the patient’s cytogenetics and baseline characteristics. Since myeloma is a disease characterized by frequent relapses with a long treatment pathway, maintaining patients QoL throughout must be a significant consideration within complex treatment decision-making. Using PROs in clinical trials will enable pharmaceutical companies and physicians to develop treatments that maintain QoL, leading to better adherence and ultimately, outcomes and experiences.