Short summary

The project will provide an essential insight into the quality of life of the general population of myeloma patients in all stages of the disease. The project includes analyses of quality of life in relation to symptom burden, complications of the cancer, side effects to treatment and functional capacity of a social, emotional and physical character. The project will clarify previously unknown knowledge of elderly, frail patients' quality of life, since knowledge of quality of life predominantly stems from clinical trials, wherefrom these patients are excluded. 

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Rationale

Multiple myeloma is a cancer of the bone marrow and the second most common type of blood cancer. In Denmark, about 320 patients are diagnosed annually with multiple myeloma. The cancer often affects older people with a median age of 69 years at diagnosis. At the end of 2013, 1611 patients were living within multiple myeloma in Denmark, of which 30 % were of working age.

Until the middle of the 1990s, the median overall survival of patients diagnosed with multiple myeloma in clinical trials was only three years. In due to improved treatment options and supportive care, the prognosis has improved markedly over the last two decades and the median survival for Danish patients under the age of 70 at time of diagnosis is now above 6-7 years. In addition, the prognosis is expected to improve further as we welcome new agents in the coming years.

Multiple myeloma is still an incurable and chronic cancer associated with severe symptoms caused by bone destruction/bone fractures, renal dysfunction, high infection rates and potential physical disability. In combination with coexistent diseases (for example lung- or heart diseases), some myeloma patients are frail, and the risk of early death among elderly patients is high.

The concept, quality of life, has been defined in many ways over the years and must be considered complex, subjective and dynamic. Health-related quality of life must be considered as a sub-element of the broader concept, quality of life, which also includes patient perceived functional capacity in everyday life. Health-related quality of life includes symptoms and complications of the disease. In the trajectory of life threatening diseases, most patients go through changes of a psychological character and adjustment reactions to the disease, a so called response shift. Response shifts can be divided into three components: Recalibration, reprioritizing and reconceptualization. These aspects should be reflected in the interpretation of quality of life studies, where change over time is monitored by patient-reported outcomes.

Systematic monitoring of quality of life over time for myeloma patients outside clinical trials has not been performed yet. In Denmark, one cross-sectional survey of health-related quality of life for patients with different types of blood cancers has been published. Only 11 % (N=54) of the participants were diagnosed with multiple myeloma, and they had the most symptoms and problems and the highest degree of severe symptoms in the survey. International cross-sectional surveys with the same outcome have been published.

Quality of life measurement is now standard in clinical trials and it typically shows improvements of quality of life during effective primary treatments for both elderly and younger patients. However, the same improvements cannot be documented in clinical trials of relapsed myeloma patients. Patients included in clinical trials are not representative of the general multiple myeloma population, whereas the cohort often is younger, has better performance status and typically a lesser degree of coexistent diseases. Quality of life for unselected myeloma patients is, for the most part, unknown. Also, there has been very little focus on the patients' quality of life in the periods off cancer treatment, leaving the time after anti-myeloma treatment understudied.

The primary aim of the project is a description of changes in quality of life over time using patient-reported outcomes measurement for the general population of multiple myeloma patients in Denmark. The description will include quality of life in relation to anti-myeloma treatment, disease- and personal characteristics. In addition, a pilot study of the prerequisites for using patient-reported outcomes measurement changes over time, so called recalibration response shift (psychological processes), will be carried out.

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Description of the cohort

Recruitment will take place in all of the 12 local hematological departments and sub-departments in Denmark. All myeloma patients requiring anti-myeloma treatment will be invited to participate in the project. The exclusion criterion is inability to read and understand the Danish language, or a psyche or mental illness, which prevents the patient of answering the questions in the questionnaires. 400 previous untreated and 400 patients at relapse patients will be included.

Data and biological material

At inclusion, demographic data will be obtained from the patient; age, gender, marital status, alcohol and tobacco consumption, level of education and work ability before and after diagnosis. To calculate MM frailty score and Freiburger comorbidity index, the patient must provide information according to Activity of Daily Living, Instrumental Activity of Daily Living and Charlson comorbidity index.

Three validated questionnaires will be used for PROM at baseline, every 4th week for the first 6 months and thereafter every 3 months until 24 months. The patients will complete the same set of questionnaires at every time point containing 82 questions in total;

• EORTC QLQ-C30 and MY20 (cancer specific)
• EORTC QLQ-CIPN20 (sensory, motoric and autonomic neuropathy)
• SF12v2-4-week-recall (generic)

For retrospective data collecting, three well established Danish registers will be used;

• Danish National Multiple Myeloma Registry; contains MM specific data on every myeloma patient diagnosed in Denmark.
• Danish Register for Evaluation of Marginalization; contains status on working capability and information on disability pension granted for every Danish citizen.
• National Patient Register; has records of the anti-myeloma treatments administered to every patient at hospitals in Denmark.

In order to clarify the impact of a recalibration response shift (psychological processes) the first 56 newly diagnosed patients entering the survey will be asked to participate in a thentest. The project manager will carry out the thentest by interviewing the patients 9 month after inclusion. The patient will answer the same 82 questions as in the set of questionnaires, but will be asked to give the answers retrospectively by thinking back at the time of inclusion. Also the patient will retrospectively give information on functional capacity of everyday living, and a new frailty score will be calculated based on the patients' self-reported conditions.

Collaborating researchers and departments

Department of Haematology, Copenhagen University Hospital

• Professor, MSc, PhD Mary Jarden
• Professor, MD, PhD Christen Lykkegaard Andersen
• Professor, MD, PhD Henrik Frederiksen
• Professor, MD, dr.med. Niels Abildgaard

Publications associated with the project

Nielsen, L.K., King, M., Möller, S. et al. Strategies to improve patient-reported outcome completion rates in longitudinal studies. Qual Life Res 29, 335-346 (2020). https://doi.org/10.1007/s11136-019-02304-8

Redder L, Möller S, Johnsen AT, Jarden M, Andersen CL, Jensen BA, Frederiksen H, Gregersen H, Klostergaard A, Steffensen MS, Pedersen PT, Hinge M, Frederiksen M, Helleberg C, Mylin AK, Abildgaard N, Nielsen LK. Quality of Life in Danish Patients with Multiple Myeloma during the COVID-19 Pandemic. COVID. 2021; 1(1):303-314. https://doi.org/10.3390/covid1010024