BACKGROUND: Cancer patients receiving immunotherapy often experience symptoms impacting their well-being. The present study aimed to develop and test the feasibility of a 12-week Technology-Enhanced Home Exercise and acupressure (TEHEplus) program to improve symptoms (fatigue, pain, sleep, anxiety, depression), social functioning, physical performance, and serum biomarkers (brain-derived neurotrophic factor, heat shock protein 90 levels.) METHODS: A two-phase design was employed. Phase 1 involved program development; Phase 2 was a pilot feasibility study. Participants with solid tumor cancers were recruited from cancer centers in Maryland and randomly assigned to four groups: Usual Care Control (UC), Technology-Enhanced Home Exercise (TEHE) alone, Acupressure alone (ACU), and TEHEplus. Feasibility was measured by enrollment duration, intervention adherence, and daily survey response rates. Outcomes were measured at baseline and program completion. RESULTS: In phase 1, four participants (age 56 to 82) provided feedback on online training, smartphone application, intervention duration, and outcome measures. In Phase 2, 40 participants (10 per group) were recruited over 12 months, with 43% (n = 17) completing all daily surveys. TEHEplus participants achieved 50% of exercise goals, and 78% adhered to the acupoint recommendations. TEHEplus participants showed significant improvements in fatigue (p = 0.02), pain inference (p = 0.30), and social functioning (p = 0.03); TEHE participants improved only in social functioning (p = 0.03). CONCLUSION: TEHEplus is feasible and shows promise for symptom alleviation. Preliminary findings suggest potential benefits in symptom management and functional outcomes. However, further studies with larger and more diverse samples are warranted to explore its efficacy and generalizability. Further studies with larger, more diverse populations are needed to confirm its efficacy. TEHEplus may enhance symptom management and improve functional outcomes for cancer survivors undergoing immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03576274 Trial Registration Date: 06/07/2018.

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