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Purpose: Multiple myeloma is a largely incurable disease. Patients suffer from the cancer, therapeutic side effects, and often psychological symptoms. Not only multiple myeloma patients but also patients with precursor diseases show high psychological distress. Today, treatment option evaluations are increasingly performed in combination with health-related quality of life (HRQoL) assessments. One factor that is positively associated with HRQoL is social support. Methods: Our recent study used questionnaires (EORTC QLQ-C30, EORTC QLQ-MY20, Illness-specific Social Support Scale) to investigate the influence of positive and negative aspects of social support on HRQoL in patients with multiple myeloma and its precursors. Results: Multiple linear regression analyses with sex, age, treatment line, hemoglobin level, and number of comorbidities as control variables show that positive social support had a significant beneficial association with emotional function (β = 0.323) and social function (β = 0.251). Detrimental interactions had a significant negative association with social function (β = − 0.209) and a significant positive association with side effects of treatment (β = 0.266). Conclusion: Therefore, screening for social support and, if needed, psycho-oncological care can be an important resource and should be implemented in routine care. Clinical trial registration: This study was registered with clinicaltrials.gov (NCT04328038). [ABSTRACT FROM AUTHOR]