Short summary

Physical exercise in patients with hematological cancer is a relevant complementary treatment, including in patients with multiple myeloma, but the evidence is sparse. The overall aim is to examine whether early initiated, individualized exercise training in patients newly diagnosed with multiple myeloma, irrespective of age and current performance status, will be beneficial for the patients´ physical function, level of physical activity and quality of life, pain and bone disease. The study is a randomized controlled trial examining the effect of supervised in-hospital exercise training sessions combined with home-based exercise training, initiated at time of diagnosis.

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Rationale

Physical exercise in patients with hematological cancer is a relevant complementary treatment, including in patients with multiple myeloma (MM). In hematological cancer, exercise is feasible, safe and beneficial in numerous aspects (aerobic capacity,muscle strength, quality of life (QOL), fatigue, psychosocial well-being, treatment-related symptoms and body composition) before, during and after stem cell transplantation. Still the evidence for the value of exercise in hematological diseases is sparse, in general and to specific diagnoses. Patients with MM may differ from other hematological diseases, by poorer functional status due to skeletal related pain, affected QOL and immune function, but also in return to work and in risk of disability pension.

Furthermore physical performance and the time of being physical active is diminished throughout the treatment course and patients do not meet physical activity guidelines. Hence, there is a need to examine the effect of exercise to be able to give evidence based recommendations on exercise in patients with MM.

The overall aim is to examine whether early initiated, individualized exercise training in patients newly diagnosed with multiple myeloma, irrespective of age and current performance status, will be beneficial for the patients´ physical function, level of physical activity and quality of life, pain and bone disease.

We will examine the effect of supervised in-hospital exercise training sessions combined with home-based exercise training, initiated at time of diagnosis. The outcomes of interest are physical function, level of physical activity, quality of life (QOL), pain and bone disease.

Furthermore, to describe the disease in patients with newly diagnosed MM in relation to physical function, level of physical activity, QOL, pain and bone condition at time of diagnosis.

The study is a two center randomized controlled trial. In total 88 patients will be included in the study. The patients will be randomized in to two groups. One group will receive usual care consisting of information about physical activity, exercise and transfer techniques. The other group will in addition receive individualized exercise training. The training consists of 8 physical training sessions supervised by a physiotherapist in a period of 10 weeks, combined with home-based training 2 times weekly and physical activity 4 times weekly. The training embodies strengthening exercise, aerobic exercise and stretching, and the patient´s bone involvement will be taken into consideration when planning the individualized exercise program.

To measure the effect of the physical exercise the patient will undergo different strength tests and 6 minute walking test. Furthermore the level of physical activity will be measured by an activity sensor. Pain and quality of life will be examined by questionnaires. Bone markers will be investigated by blood tests, and DEXA scans will be performed to examine body mass and bone mineral density. Finally, the patients will keep physical training logs.

These tests and examination will be performed at baseline and after 11 weeks, 6 months and 12 months. The level of physical activity will also be examined after 4 weeks and 7 weeks.

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Description of the cohort

All patients with newly diagnosed MM at Zealand University Hospital, Roskilde and Odense University Hospital will be screened for eligibility on the basis of inclusion and exclusion criteria at time of diagnosis.

Inclusion criteria: Adult patients >18 years newly diagnosed with MM requiring treatment. The patient must be able to speak and understand Danish and be able to give his/her informed consent.

Exclusion criteria: Patients with spinal cord compression, unstable vertebral fracture (SINS score >12), untreated cardiac failure and untreated cardiac arrytmia, severe chronic cardiac failure (NYHA 3-4), other severe comorbidity that will not allow physical training, e.g. neurological or uncompensated liver failure and psychologic or psychiatric disorder that will not allow compliance in physical training.

Data and biological material

Knee extension strength measured by a static strength test by using hand-held dynamometer.

Grip strength and Sit-to-Stand test.

Submaximal aerobic capacity measured by 6 Minute Walking Test.

QOL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core Questionnaire (EORTC QLQ-C30) and The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Multiple Myeloma Module (EORTC QLQ-MY20).

Pain measured by Brief Pain Inventory (BPI) in the Danish short version, reported by patients.

Level of physical activity will be measured by accelerometer (ActivPal) for a period of 5 days.

Bone disease will be measured in two ways; 1. Osteoblast and osteoclast activity measured by dynamic markers (PINP and CTX-1) of bone metabolism in serum. 2. Bone mineral density (BMD) measured by DEXA scans of whole body, lumbar spine and hip, and lean body mass will be measured too.

Furthermore demographic and medical data will be collected and patients will keep physical training logs.

Collaborating researchers and departments

The Haematological Research Unit, Department of Clinical Research, University of Southern Denmark and Department of Haematology, Odense University Hospital

• Professor and Consultant Niels Abildgaard

Hospitals Center for Health Research, Copenhagen University Hospital

• Senior Researcher Mary Jarden, PhD

Department of Rehabilitation, Odense University Hospital

• Lisbeth Rosenbek Minet, PhD

Department of Haematology, University Hospital Roskilde

• Consultant Ulf Christian Frølund

Department of Clinical Biochemistry, University Hospital Roskilde

Department of Medicine, Section of Endocrinology, University Hospital Køge

Department of Endocrinology, Odense University Hospital