Annual Meeting Proceedings Part 1 - American Society of Clinical ...

9081 General Poster Session (Board #43D), Sat, 8:00 AM-12:00 PM
Inflammatory markers and symptom burden in patients with multiple
myeloma undergoing autologous stem cell transplantation. Presenting
Author: Loretta A. Williams, University of Texas M. D. Anderson Cancer
Center, Houston, TX
Background: We explored the association between activation of inflammatory
networks and development of severe symptoms during mobilization
and the acute phase of autologous hematopoietic stem cell transplantation
(ASCT) for multiple myeloma (MM). Methods: From mobilization through
the first 3 months after ASCT, multiple symptoms were measured repeatedly
via the myeloma module of the M. D. Anderson Symptom Inventory
(MDASI-MM). Serum levels of interleukin (IL)-6, IL-10, tumor necrosis
factor (TNF)-a, soluble TNF receptors 1 and 2 (sTNF-R1, sTNF-R2), IL-1
receptor antagonist (IL-1RA), vascular endothelial growth factor (VEGF),
macrophage inflammatory protein-1 (MIP-1a), monocyte chemoattractant
protein (MCP)-1 and C-reactive protein (CRP) were collected up to 11 times
per patient and assayed by Luminex. Ordinal regression modeling was used
to analyze repeated-measures data. Results: Among50 MM patients, the
most severe symptoms reported by werefatigue, pain, muscle weakness,
disturbed sleep, drowsiness, numbness, poor appetite, and bone aches.
Symptoms worsened rapidly from conditioning therapy and peaked at WBC
nadir. Over time, controlling for age, sex, and MM stage, increased serum
IL-6 (P�.0007) and MCP-1 (P�.0005) were significantly associated with
worsening of the most severe symptoms; MIP-1a (P�.005) and VEGF
(P�.002) were inversely associated with these symptoms. Increased CRP
was significantly associated with worsening pain (P�.01), fatigue (P�.007),
and bone aches (P�.006). Conclusions: This longitudinal study indicates a
strong association between dynamic changes in circulating inflammatory
molecules and the most severe symptoms in MM patients during the acute
phase of ASCT. This observation, similar to IL-6-related multisymptom
development around WBC nadir of allogeneic SCT (Wang et al, 2008),
provides evidence of potential inflammation-induced behavioral changes in
humans. Testing of anti-inflammatory interventions is warranted to further
confirm the role of inflammation in the development of symptoms and
identify effective mechanism-driven symptom management during ASCT.
9083 General Poster Session (Board #43F), Sat, 8:00 AM-12:00 PM
Longitudinal relationship between inflammatory markers and patientreported
symptom severity during induction therapy for multiple myeloma.
Presenting Author: Mary H. Sailors, University of Texas M. D. Anderson
Cancer Center, Houston, TX
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 antiinflammatory
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: Bortezomibbased
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-1� 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.
Patient and Survivor Care
587s
9082 General Poster Session (Board #43E), Sat, 8:00 AM-12:00 PM
Baseline subclinical sensory deficits and the development of pain and
numbness in patients with multiple myeloma (MM) being treated with
chemotherapy. Presenting Author: Elisabeth G. Vichaya, University of
Texas M. D. Anderson Cancer Center, Houston, TX
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a
dose-limiting toxicity experienced by patients with MM. Patients may
develop painful and non-painful (e.g., numbness) symptoms that impair
function and often persist after therapy is terminated. This study examined
the predictive value of baseline subclinical sensory deficits on the development
of treatment-related pain and numbness. Methods: Patients (N�56)
who had two or fewer cycles of induction therapy and no obvious
neuropathy were assessed for sensory deficits using quantitative sensory
testing (QST). Patients reported the severity of pain and numbness (on a
0-10 scale) at least weekly via the MD Anderson Symptom Inventory during
induction (up to 16 weeks); 15 of 56 patients provided data for up to 16
additional weeks of maintenance therapy. These values correlate to patient
reported pain and numbness in the hands/feet. Based on data collected
from healthy controls, patients were classified as being with or without a
sensory deficit at baseline on each QST domain. We fit linear mixed models
for pain and numbness with each sensory deficit and time, controlling for
cumulative cycles, diabetes, age, and treatment agent. Data is shown as
mean � standard deviation. Results: Patients who showed baseline deficits
in sharpness detection (20%) reported significantly lower levels of pain
(1.2�1.9 vs 3.1�2.9, p�.004) and numbness (0.4�0.8 vs 2.4�2.6,
p�.001) during induction therapy and less numbness (0.0 vs 3.5�2.8,
p�.001) during maintenance therapy. Further, those who showed deficits
in warmth detection (40%) reported higher levels of pain (5.2�2.8 vs
1.7�2.3, p�.001) and numbness (5.8�2.2 vs 1.6�1.8, p�.001) during
maintenance therapy. Finally, those with lower skin temperature (47%)
reported higher levels of pain (4.5�2.3 vs 1.7�2.9, p�.005) during
maintenance therapy. Conclusions: Our results suggest that subclinical
sensory deficits may be useful in determining a patient’s risk for developing
CIPN prior to initiation of induction therapy. This information could be used
to provide patients with more-personalized chemotherapy plans that take
into account their neuropathy risk.
9084 General Poster Session (Board #43G), Sat, 8:00 AM-12:00 PM
Randomized trial of a physical activity intervention in patients with
metastatic breast cancer. Presenting Author: Jennifer A. Ligibel, Dana-
Farber Cancer Institute, Boston, MA
Background: Physical activity (PA) interventions improve fitness, functional
capacity, and quality of life in patients with early-stage breast cancer.
There are almost no data regarding the feasibility or potential benefits of PA
in women with metastatic breast cancer (MBC). Our study evaluated the
impact of a moderate-intensity PA intervention upon functional measures
in patients with MBC. Methods: Participants were randomized 1:1 to a
16-week PA intervention or usual care control group. Eligibility included
diagnosis of MBC, ECOG 0-1, and no active brain metastases. The
intervention consisted of 4 weekly meetings with an exercise physiologist,
followed by monthly in-person and weekly telephone-based meetings. The
PA goal was 150 minutes per week. Baseline and 16-week evaluation
included: modified Bruce treadmill test, 7-Day Physical Activity Recall
Interview, and EORTC QLQ C-30 questionnaire. Results: 101 women
enrolled between 9/06 and 3/11. Median age was 49 years, median time
since diagnosis of MBC was 1.1 years, 48% of participants were on
hormonal therapy and 42% on chemotherapy/biologic therapy. 69%
completed all study measures (an additional 9% all but the final treadmill
test). Attrition was higher in the intervention arm (30% vs. 16%, p�0.15).
Outcome measures are shown in table below. Both groups experienced
improvements in treadmill times. Intervention participants also reported
improvements in physical functioning and increased minutes of weekly PA,
with a trend toward significant differences between groups. Conclusions:
Women with MBC participating in a PA intervention experienced consistent,
but non-significant, trends toward improvements in functional measures.
Our sample size was small, limiting power to evaluate the potential
benefits of PA in women with MBC. Additional work is warranted,
particularly since PA interventions appear feasible in this patient population.
Baseline Change over 16 weeks
Exercise Control Exercise Control p value
Treadmill (min)* 5.6 � 1.8 5.3 � 1.7 .61 � .19** .37 � .16** .35
Physical functioning* 84.2 � 14.4 83.9 � 13.2 4.79 � 2.40** .93 � 2.07 .23
Exercise min/wk* 86.3 � 217.8 74.7 � 80.6 71.8 � 185.6** 53.8 � 183.7 .14
*Data presented as means � SD. **Within-group comparison �0.05.
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