Researchers from the M.D. Anderson Cancer Center, Houston, TX, have investigated the association between molecular inflammatory markers in multiple myeloma and patient outcomes in 2 recent studies. In the first study, the researchers have correlated the expression of inflammatory markers and the occurrence of disease- or treatment-related complications in patients with myeloma. In the second study, the researchers focused on inflammatory markers that may be predictive of the development of symptom burden during aggressive treatments, such as autologous stem-cell transplant (ASCT). Such data could help predict which patients are likely to have disease- or treatment-related complications.
Inflammatory Markers Mirror Disease- or Treatment-Related Complications
The first study included 59 patients with myeloma; of these, 37% patients were treatment-naïve (Sailors MH, et al. J Clin Oncol. 2012;30[15S]:Abstract 9083). The patients were asked to rate their symptoms twice weekly during induction therapy (89% received bortezomib). Symptoms were assessed 8 days before induction therapy and up to 112 days after the start of treatment. The investigators adjusted the analysis for age, sex, body mass index (BMI), staging, and tumor response.
Patients contributed serum samples before the start of every chemotherapy cycle, which were then evaluated for proinflammatory and anti-inflammatory cytokines. The presence of cytokines was correlated with symptom expression, which was adjusted according to patient and clinical factors.
“Fatigue was persistently the most severe symptom during induction therapy, followed by disturbed sleep, muscle weakness, pain, drowsiness, and bone aches,” reported Mary H. Sailors, PhD, Supervisor and Data Analyst at M.D. Anderson Cancer Center. Chemotherapy-induced peripheral neuropathy also significantly worsened from baseline.
Over the induction period, tumor necrosis factor–receptor (TNF-R) I and TNF-RII serum levels were significantly associated with self-reported pain, drowsiness, and numbness over the induction therapy period, and interleukin-6 was associated with drowsiness and numbness.
“Cytokine fluctuations during induction therapy in patients with multiple myeloma may be part of the underlying biological mechanism that drives symptom burden,” Dr Sailors suggested. “Frequent assessment can document the longitudinal course of multiple symptoms during induction and provide an opportunity to evaluate systemic inflammation as a potential source of symptom burden during induction therapy,” Dr Sailors added.
Inflammatory Markers Associated with Worsening Symptoms
In the second study, researchers looked at inflammatory markers that might be predictive for the development of symptom burden during aggressive treatments, such as ASCT (Williams LA, et al. J Clin Oncol. 2012;30[15S]:Abstract 9081). The study enrolled 50 patients scheduled for transplant, from whom serum samples were collected up to 12 times per patient. Symptoms were evaluated twice weekly, from stem-cell mobilization through the first month after transplant.
The most severe symptoms were fatigue, pain, muscle weakness, disturbed sleep, drowsiness, numbness, poor appetite, and bone aches. Symptoms worsened rapidly from mobilization and peaked at white blood cell nadir.
Inflammatory markers were significantly associated with worsening of the symptoms over time, in an analysis that controlled for age, sex, BMI, and disease stage.
“Our longitudinal study indicated a strong association between dynamic changes in circulating inflammatory molecules and the most severe symptoms among myeloma patients during the acute phase of transplant,” reported Loretta A. Williams, PhD, MSN, RN, Instructor, Department of Symptom Research at M.D. Anderson Cancer Center and an advanced oncology-certified nurse.
She said that testing of anti-inflammatory interventions is warranted to further confirm the role of inflammation in the development of symptoms and to identify effective mechanism-driven symptom management during ASCT.