Effects of a Resistance Physical Exercise Program in Multiple Myeloma Patients

The primary outcome measure will be health related quality of life. Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Specifically, the EORTC QLQ-C30 will be used, which is widely used to assess quality of life in cancer patients [X]. This instrument consists of 30 items, 24 of which are grouped into five functional domains: physical, role, emotional, cognitive, and social. It also includes three symptom scales-fatigue, pain, and nausea/vomiting-and an overall health status scale. Six other items assess additional symptoms such as dyspnoea, loss of appetite, insomnia, constipation, diarrhoea, and financial difficulties. Responses are recorded on a four-point scale ('none,' 'a little,' 'quite a bit,' 'a lot'), except for the general health and quality of life scales, which use a seven-point format. On the functional and overall health scales, higher scores indicate better health, while on the

Frailty will be assessed using the Short Physical Performance Battery (SPPB) scale [X], which comprises three components: a balance test, a gait speed test, and a chair rise test. The maximum possible score is 12 points, with higher scores reflecting a better level of physical function.

The presence of anxiety and depression will be assessed using the Hospital Anxiety and Depression Scale (HADS), a validated questionnaire widely used in different populations [X]. The scale consists of 14 items: seven corresponding to the anxiety subscale (HADS-A) and seven to the depression subscale (HADS-D). Each item is scored from 0 to 3, with separate scores obtained for both emotional dimensions.

Fatigue will be measured using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) subscale [X], a self-reported instrument designed to assess the severity of fatigue in cancer patients [X,X]. This widely used tool combines the 27 items of the FACT-General with 13 additional fatigue-specific items, generating a total score range between 0 and 160. Higher scores indicate lower perceived fatigue levels.

Sleep quality will be assessed using the Athens Insomnia Scale (AIS), an eight-item self-administered scale developed by Soldatos [X] and validated for use in the Spanish population [X]. The first five items assess sleep disturbances-sleep onset, night-time awakenings, early awakening, total sleep duration, and overall quality-corresponding to criterion 'A' for the diagnosis of insomnia according to the ICD-10 classification. The remaining three items assess daytime consequences (well-being, physical and mental functioning, and daytime sleepiness), aligned with criterion 'C' of the same classification.

Each item is scored on a Likert scale from 0 ('no problem') to 3 ('significant problem'), yielding a total range of 0 to 24. Higher scores indicate greater sleep disturbance, and values equal to or greater than 6 are considered indicative of clinically relevant insomnia [X].

The overall level of physical activity will be determined using the Spanish version of the International Physical Activity Questionnaire (IPAQ) [X]. This questionnaire consists of seven questions that assess the duration and frequency of physical activities of varying intensity:

• Light activity (<600 MET-minutes/week), such as walking at home, at work or during leisure time.
• Moderate activity (600-3000 MET-minutes/week), such as cycling, playing tennis or carrying light objects.
• Vigorous activity (>3000 MET-minutes/week), which includes intense exercises such as aerobics, digging or weightlifting.

The IPAQ also records the amount of time spent being inactive during the past week, providing a comprehensive overview of the participant's activity levels. The total physical activity score is calculated by adding up the vigorous, moderate and light activities expressed in MET-minutes/week [X].

Various variables related to the participants' body composition will be collected. Height will be measured using a height gauge, and the rest of the parameters will be obtained by electrical bioimpedance, using the TANITA BC-418® device. The variables will include total body weight and appendicular muscle mass (ASM), defined as the sum of the muscle mass of the limbs. To calculate the appendicular muscle mass index (ASMI), the height-adjusted formula (AMM/height²) will be applied [X].

Parameters such as visceral fat, body fat percentage (BF%), and body mass index (BMI) will also be assessed. To ensure the accuracy of the measurements, all participants will be weighed wearing minimal clothing and barefoot, thus reducing variability and ensuring that the results reliably reflect actual body composition [X].

The strength of the upper and lower limbs will be assessed using different procedures. For handgrip strength, the Jamar® hydraulic dynamometer (J00105, Lafayette Instrument Company, USA) will be used, which is considered the gold standard for this type of measurement [X]. Both hands will be assessed following the Southampton Protocol [X]. The participant will sit in a chair with a backrest, with the shoulder adducted and in neutral rotation, the elbow flexed at 90°, the forearm in a neutral position and the wrist in slight extension (0°-30°).

Three consecutive measurements will be taken on each hand, with 5-second contractions and 10-second breaks between them. During the test, the participant will be encouraged to exert maximum effort. The second position of the dynamometer will be used in all cases, except for small hands, where the first position will be used (duly recorded). The same evaluator will perform all measurements, and the average or maximum value for each hand will be co

In addition to the SPPB, physical performance will be assessed using the four-metre walk test (4MWT), a complementary indicator of frailty. The participant will begin walking one metre before the starting line, where the stopwatch will be started, and will continue at their usual speed until four metres beyond the finish line. The test will be repeated three times and the best time achieved will be recorded