To our knowledge, this was the first report of SC investigation in MM. In this study, we identified three SCs in 174 MM patients who had been treated in the hematology day unit in our institute. The first SC was psychological SC which included symptoms of feeling nervous, worrying and feeling sad. Although the specific symptom items might be different in the cluster, psychological SC has been demonstrated as a common SC in patients with cancer, either solid tumor or hematological malignancy[5–7]. Specific psychological symptom in MM had been reported in previous studies[19]. Ramsenthaler et al. found that almost one third of MM patients claimed anxiety[10]. Our data showed that in psychological SC, the patients with severe symptom distress were younger than those with mild symptom distress. Van der Poel et al. also reported that elderly MM patients (> 65 years) had better emotional functioning than young patients(≤ 65 years)[20]. The reason for such difference was still unknown. It might be because elderly patients had better coping strategies due to more life experience than that of young patients. Furthermore, in agree with previous studies, our data suggested that more female patients reported severe symptom distress of psycological SC than the male[7, 21]. At last, the distress of psychological SC was influenced by the patients’ treatment outcome. Patients with treatment response < PR, anemia, or serum lactate dehydrogenase > 220 IU/L were likely to report severe symptom distress of psychological SC than the counterpart patients. The pain-dry mouth-difficulty sleep SC was also identified in our MM patients. Studies have shown that pain and sleep disturbance are always co-existing in a SC in cancer patients[22–24]. Krause et al. showed that sleep deprivation enhanced pain responses within the primary sensing regions in the brain, and weakened the activity in other regions that modulated pain processing[25]. Such findings provided physiology evidences of co-existence of pain and sleep disturbance in cancer patients. The symptoms of pain and sleep disturbance were reported in MM patients[26, 27]. In our study, the female patients were more likely to be bothered by pain-dry mouth-difficulty sleep SC. It’s consistent with the fingdings that the female had lower pain acceptance than male[28] and being female was significantly associated with poor sleep[29]. We also found that the patients with diabetes reported severe distress of pain-dry mouth-difficulty sleep SC. Dry-mouth symptom was commonly seen in diabetes. If the MM patients had diabetes, the dry-mouth symptom might be even worse. At last, the severity of the MM disease and the treatment outcome highly affected the distress of pain-dry mouth-difficulty sleep SC. In this study, the symptoms of feeling drowsy, difficulty concentrating, and lack of energy were categorized into the fatigue SC, which include physical and cognitive fatigue. Fatigue is the most frequent symptom reported in MM patients, with a high prevalence of 55%ཞ98.8%[11, 26, 27]. We found that the patients with a long time since diagnosis (≥ 24 months), bad treatment response (< PR), relapsed or refractory disease, and MLR ≥ P50 (0.39) tended to report severe symptom distress of fatigue SC than the counterpart patients. Mols et al. found that patients with MM complained a significant increase of fatigue from baseline to one year follow-up[30]. Previous study also observed that the fatigue were significantly higher in relapsed or refractory MM patients than the control group[31]. Furthermore, Shi et al. reported that elevated MLR (cut-offs of 0.3) predicted poor clinical outcome in MM patients[32]. In this study, we found the increased MLR was associated with severe symptom distress of fatigue SC. Therefore, the MLR may serve as a cost-effective and available predictive biomarker for fatigue SC in MM.
QOL improvement is one of the most important goals for MM management. Based on our findings, the MM patients with severe symptom distress in psychological SC, pain-dry mouth-difficulty sleep SC and fatigue SC had inferior QOL in all domains and overall scores. These results are consistent with the previous studies in other cancer[33–35]. Although no studies had assessed the correlation between SCs and QOL in MM patients, the correlations between specific symptoms and QOL had been addressed in MM. For example, symptoms of pain, fatigue, anxiety, and depression correlated with QOL in MM[9, 11]. With the determinant role of symptom distress in cancer patients’ QOL, one unique feature of MM, compared with other cancers, was that the overall survival of MM was significantly prolonged in the past decades, yet the disease was still incurable. Thus, living with cancer and experiencing multiple rounds of treatment might be more common in MM patients than patients diagnosed with other human cancers. At least for some patients, MM might be considered as a chronic disease, and QOL for those patients was as important as the outcome of cancer therapy. Targeting to the SCs rather than single symptoms allows for more thorough symptom assessment, simplified interventions and more efficient symptom managment[8]. Additionally, because individual symptoms of MM are associated with decreases in QOL[9, 10], it’s logical that clusters of symptoms may have greater impact on QOL than single symptoms. Therefore, our data provided first-hand evidence to show that the inter-correlations of the MM disease status, SC and QOL. Our data also encouraged health care givers’ attention to specific patient groups, such as young female MM patients.