Longitudinal relationship between inflammatory markers and patient-reported symptom severity during induction therapy for multiple myeloma.

Abstract

9083 Background: Multiple myeloma (MM) patients undergoing induction therapy experience both disease- and therapy-related symptoms. We investigated the association between the trajectory of symptom severity and changes in levels of inflammatory markers. Methods: MM patients (N=62) rated symptoms via the M. D. Anderson Symptom Inventory (MDASI) twice a week during induction therapy. Patients contributed serum samples before the start of every chemotherapy cycle. A panel of pro- and anti-inflammatory cytokines and markers was evaluated by Luminex. Ordinal regression analyses were used to describe the relationship between cytokines and symptom outcomes across time. These analyses were adjusted for patient and clinical factors (age, sex, diabetes diagnosis, anemia, BMI, comorbidity, staging, ECOG PS, prior treatment status, tumor response, opioid use, and chemo regimen). Results: Bortezomib-based induction therapy was received by 89% of the sample. Fatigue was persistently the most severe symptom during induction therapy, followed by disturbed sleep, muscle weakness, pain, drowsiness, and bone aches. Numbness, which is representative of chemotherapy-induced peripheral neuropathy, significantly worsened from baseline (p=0.01). We observed significant longitudinal associations between sIL-1R1 and distress and sadness (both p=0.02); between sIL-6R and disturbed sleep (p=0.001), poor appetite (p=0.04), and sore mouth (p=0.006). IL-6 was significantly associated with pain, fatigue, nausea, and sore mouth (all p<.05). A negative association between sTNF-RII and pain, sleep, distress, remembering, poor appetite, and nausea (all p<0.05) was also observed. MCP-1 was positively associated with numbness (p=0.04); while MIP-1α was negatively associated with sleep, numbness, constipation, poor attention (all p<0.01), and bone aches (p=0.0006). IL-10 was negatively associated with mood interference (p=0.04). Conclusions: Frequent assessment can document the longitudinal course of multiple symptoms during induction and provides opportunity to evaluate systemic inflammation as a potential source of symptom burden during induction therapy for MM.