Effects of Controlled Breathing Added to Therapeutic Exercise in Multiple Myeloma

Randomized, parallel, double-blind, controlled clinical trial in which two groups of participants will be included and randomly assigned to one of the two intervention arms:

Therapeutic exercise + initial educational session on proper breathing.

Therapeutic exercise + initial educational session on proper breathing + home-based controlled breathing exercise protocol.

The therapeutic exercise and controlled breathing program will last 6 weeks. During this period, participants will:

Perform three weekly sessions of mobility and muscle-strengthening exercises (two on-site and one home-based) for 6 weeks. The on-site sessions will last between 30 and 40 minutes and will take place at the Rehabilitation Department of Hospital 12 de Octubre in Madrid (a total of 12 on-site sessions-two per week). The home-based exercise program will consist of completing, once per week during the 6-week intervention, a structured session that replicates the logic and technique of the on-site program.

Walk a minimum of 7,000 steps/day or 50 minutes/day, three days per week.

Perform a controlled breathing protocol twice per day at home during the 6-week study period, following the recommendations of the principal investigator. The goal is to integrate slow, gentle, diaphragmatic, nasal breathing into daily life.

The variables to be assessed will include: somatic symptom questionnaire, quality of life, sleep quality, fatigue, anxiety and depression symptoms.

These variables will be evaluated at baseline, at the end of the 6-week intervention period, and again 4 weeks after completing the intervention.

Inclusion criteria

• Age ≥ 18 years.
• Confirmed diagnosis of multiple myeloma, currently undergoing active treatment with daratumumab, and under clinical follow-up by the Hematology Department of HU12O.
• Explicit medical indication for supervised physical activity issued by the responsible hematologist and documented in the medical record.
• No scheduled hematopoietic stem cell transplantation within the 60 days following the planned start date of the intervention (verified through medical record review).
• Functional status of ECOG 0-2 (Eastern Cooperative Oncology Group), assessed by a healthcare professional from the Hematology Department, ensuring the ability to perform at least basic and light instrumental activities of daily living, including independent ambulation.
• Access to a smartphone with stable internet connection, required for monitoring and recording adherence to the intervention.
• Ability to provide written informed consent, demonstrating understanding of the study's nature, purpose, and procedures.

Exclusion criteria

• Medical risk contraindicating exercise or breathing techniques:

+Clinically significant cardiovascular disease, including: decompensated heart failure, acute myocardial infarction within the past 3 months, clinically uncontrolled arrhythmias, unstable angina, acute-phase deep vein thrombosis or pulmonary embolism, pacemakers or cardiac devices whose monitoring parameters contraindicate supervised exercise according to cardiology.

• Severe decompensated respiratory disease, such as acute exacerbation of COPD, severe respiratory insufficiency, or persistently low resting oxygen saturation < 90% (not correctable).
• High musculoskeletal or bone risk:

• Extensive lytic bone lesions, high risk of pathological fracture, or unstable vertebral fracture, documented by imaging or based on the assessment of the Hematology/Traumatology specialist.
• Uncontrolled pain that prevents safe participation in an exercise program.
• Hematologic or systemic conditions contraindicating exercise:

• Severe anemia: hemoglobin < 9 g/dL in women or < 8 g/dL in men (latest laboratory test ≤ 14 days).
• Active systemic infection contraindicating exercise, fever ≥ 38 °C, or neutropenia < 0.5 × 10⁹/L.
• Severe cytopenias that, in the opinion of the hematologist, preclude moderate exercise.
• Functional or procedural limitations:

• Inability to remain in the supine position for ≥ 5 minutes, required for part of the breathing intervention.
• Confirmed pregnancy or reasonable suspicion of pregnancy.
• Severe cognitive impairment, major psychiatric disorders, or neurological diseases that limit understanding of the procedures or safe participation.
• Significant difficulty understanding the language (spoken or written) that prevents following essential instructions or completing validated questionnaires.