The Longitudinal Relationship Between Inflammatory Markers and Patient-Reported Symptom Severity During Induction Therapy for Multiple Myeloma

Patients with multiple myeloma (MM) undergoing induction therapy experience both disease- and therapy-related symptoms. This longitudinal study investigated the association between the trajectory of symptom severity and changes in levels of inflammatory markers.

Patients with MM repeatedly rated symptoms via the M. D. Anderson Symptom Inventory (MDASI) during induction therapy. Patients contributed serum samples before start of every cycle of chemotherapy. A panel of cytokines, including interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), soluble IL-1 receptor type 1 (sIL-1R1), soluble tumor necrosis factor receptor type 2 (sTNF-R2), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1A), and IL-10, was examined by Luminex method. Ordinal regression analyses were used to describe the interaction of cytokines and symptom outcomes across time, adjusted for patient and clinical factors of age, sex, diabetes diagnosis, anemia, body mass index, co-morbidities, tumor stage, Eastern Cooperative Oncology Group performance status (ECOG PS), prior treatment status, tumor response, opioid use, and chemotherapy regimen.

Sixty-two patients were enrolled on study; of these, 89% received bortezomib-based induction therapy. During induction, the most severe patient-reported symptoms were (in order of severity): fatigue, muscle weakness, disturbed sleep, pain, drowsiness, bone aches, and numbness. Fatigue was persistently the most severe symptom, while therapy-induced neuropathy (MDASI numbness item) increased significantly from baseline (P=.01). We observed significant longitudinal associations between sIL-1R1 and distress and sadness (both P=.02); between sIL-6R and disturbed sleep (P=.001), poor appetite (P=.04), and sore mouth (P=.006); between IL-6 and pain, fatigue, nausea, and sore mouth (all P<.05); and negative associations between sTNF-R2 and pain, sleep, distress, difficulty remembering, lack of appetite, and nausea (all P<.05). MCP-1 was positively associated with numbness (P=.04). MIP-1A was negatively associated with disturbed sleep, numbness, constipation, difficulty paying attention (all P<.01), and bone aches (P=.0006). IL-10 was negatively associated with mood interference (P=.04).

Frequent assessment documented the longitudinal course of multiple symptoms during the induction period, providing an opportunity to evaluate potential changes in inflammation as one source of symptom distress. Our preliminary study suggests a network of pro- and anti-inflammatory cytokines relevant to symptom expression during induction. The results warrant further basic and translational studies to confirm the role of inflammation in the development of symptoms during treatment. Such information may suggest methods of effective symptom management and identify potential biomarkers for patients at high risk of symptom burden during treatment for multiple myeloma.

No relevant conflicts of interest to declare.