Trajectory, Interactions, and Predictors of Higher Symptom Burden During Induction Therapy for Multiple Myeloma

Background: Patients with multiple myeloma (MM) experience disabling symptoms that are difficult to manage and may persist after induction therapy. Monitoring disease-related and induction therapy-induced symptoms and identifying patients at greater risk for high symptom burden are unmet clinical needs. The objective of this study was to examine the trajectories of symptom severity over time and identify predictors of high symptom burden during MM induction therapy.

Methodology: Eligible patients with MM rated their symptoms by completing the MD Anderson Symptom Inventory MM module repeatedly during 16 weeks of induction therapy. Group-based trajectory modeling identified patient groups with persistently high-severity (versus low-severity) symptom trajectories over time. Quality of life (QOL) and affective and physical functioning status were assessed. Predictors of high symptom burden were examined by regression analysis.

Results: Sixty-four MM patients participated. Most patients (89%) received bortezomib-based therapy. The five most-severe symptom trajectory groups were pain (59%), muscle weakness (46%), numbness (42%), disturbed sleep (41%), and fatigue (31%). Patients in the high-severity trajectory group for the five most-severe symptoms (31% of the sample) were more likely to have high-severity cognitive and affective symptoms. Patients in the high-severity trajectory groups for fatigue, muscle weakness, disturbed sleep, and bone aches were more likely to have high pain scores (all p < 0.05). Significant increases over time were observed in scores for pain (estimate: 0.026), numbness (0.051), muscle weakness (0.020), physical items (0.028), and affective items (0.014) (all p < 0.05). A higher baseline composite score of the five most-severe symptoms predicted worse QOL (- 6.24), and poor affective (0.80) and physical (1.10) statuses (all p < 0.01). Female sex predicted higher risk for being in the high-severity trajectory group for muscle weakness.

Conclusion: Almost one-third of MM patients suffer from up to 5 moderate to severe symptoms persistently, including pain, muscle weakness, numbness, disturbed sleep, and fatigue. Importantly, these results identify a group of symptoms that should be monitored and managed as part of routine patient care during MM induction therapy and suggest that pre-therapy pain management is necessary for better symptom control.