Assessing safety and feasibility of targeted exercise to suppress bone disease in multiple myeloma patients.

A two-armed, single-blinded (investigators blinded to allocation) randomised and controlled (supervised exercise versus usual medical care) trial is proposed to examine the safety and feasibility of a supervised, targeted and dose-escalated exercise medicine program for multiple myeloma patients with myeloma bone disease. Exercise sessions will be conducted in a small group setting (of up to 6 persons per group) in an exercise clinic suitable for persons with chronic disease including cancer. Resistance exercises will occur through using pin-loaded weight machines, cable resistance machines, smith machines and free weights (dumbbells or barbells). Isometric exercises require body-weight only with no specific or special equipment necessary. Aerobic exercises occur through standard ergometers (such as a treadmill, stationary cycle, arm cycle, or rower). Intervention adherence and fidelity will be assessed through exercise record logbooks of prescribed versus actual completed (exercises and volume-load), as well as attendance rate to planned exercise sessions. The exercise arm (intervention) will receive an individually tailored exercise program involving isometric, resistance and aerobic exercise of moderate-to-vigorous intensity in addition to usual medical care. Participants assigned to the exercise arm will be required to participate in a modular, multi-modal exercise program for 12 weeks, including resistance exercise, aerobic exercise and isometric exercise. The program requires participants to attend three clinic-based exercise sessions per week for 60 minutes in duration, supervised by accredited exercise physiologists with experience delivering exercise to patients with advanced cancers. As multiple myeloma patients with myeloma bone disease may have stable and unstable skeletal structures dependent upon magnitude of disease infiltration, the exercise program will be individually tailored for each patient according to their clinical presentation. For stable disease-affected bones, a dose-escalation approach will be employed to graduate load from isometric to dynamic mechanical stimuli over the program through targeted muscle contraction and mild to moderate external resistance activities as tolerated. Exercise doses will be escalated if the target lesion sites are asymptomatic and exercises well-tolerated, determined in routine consultation with the participant. Unstable disease-affected bone sites will be avoided in accordance with our teams established modular exercise program used in prior studies with bone metastases. Exercise of regions unaffected by myeloma bone disease will be prescribed as normal, without modifications. Resistance exercise will incorporate repetition maximums (RM), with six different resistance exercises using major muscle groups, subject to the location and extent of skeletal lesions, at 8–12 RM for three sets per exercise to achieve a moderate intensity and volume. Aerobic exercise will be set at a heart rate (HR) with moderate-to-high intensity exercise shown to reduce circulating tumour cells in colorectal cancer patients. Accordingly, participants will engage in aerobic exercise using treadmill, cycling and rowing ergometers, performed at 60–85% HRmax for 20–30 minutes (moderate-intensity continuous training) or 4 bouts of 4 minutes per bout at 85-95% HRmax (high-intensity interval training) tracked with heart rate monitors. Isometric exercise will require particular positions to be adopted that ensure high levels of muscular contraction to hold stable body positions that ensure the joint(s) surrounding the target bone do not move while the muscle around it contracts. Flexibility exercise will involve static stretching of muscles at all joints considered important for function, and for all muscles engaged during the session, except for locations of unstable lesion sites. Stretches will involve 2–4 sets with 30–60 s hold per set.