ALBERT

Description: Key Points The MD Anderson Symptom Inventory for CML can be used to collect patient-reported symptoms for research and clinical practice. Thirty percent of patients in chronic-phase CML and on TKIs experience moderate symptoms that interfere with daily functioning.

Description: Abstract 2953 Multiple myeloma (MM) is an incurable cancer characterized by the clonal proliferation of plasma cells within the bone marrow. Current treatment for most patients with newly diagnosed MM includes induction therapy (typically dexamethasone plus thalidomide or bortezomib for patients eligible for autologous stem cell transplantation [AuSCT], melphalan and prednisone, with or without thalidomide, for those ineligible for transplantation), followed by consolidation with high-dose melphalan and AuSCT for transplant-eligible patients, and finally maintenance therapy. Intensive induction therapy and AuSCT produce superior outcomes in younger patients (

Description: Abstract 4734 Background: Disease progression in multiple myeloma (MM) is highly related to cytokines, particularly interleukin (IL)-6, which promotes the growth of MM and is essential for the proliferation of malignant plasma cells. However, there are few reports delineating the relationship between levels of circulating cytokines and the severity of symptoms that patients experience during induction therapy. Methods: Thirty-four patients with MM were enrolled in this ongoing study before or within 2 cycles of induction therapy (with majority of bortezomib based and few thalidomide based). Multiple symptoms were measured by M. D. Anderson Symptom Inventory – MM module (MDASI-MM) twice a week during induction therapy. Sera were collected at baseline and during every cycle of induction therapy to measure cytokines by Luminex Multiplex Bead Array assay. Using ordinal regression models, we examined the hypothesis that concentration of serum inflammatory cytokines would be associated with symptom burden in patients with MM during induction therapy, especially therapy induced symptoms. The modeling was adjusted for time from induction therapy, age, sex, staging, Eastern Cooperative Oncology Group performance status (PS), opioid use, and body mass index (BMI). Symptom severity ratings were treated as ordinal responses. A log scale of cytokine concentrations was used for modeling. Results: From longitudinal symptom profile modeling, in general, female patients and patients with poor PS (PS ≥ 2) reported significantly higher level of symptoms than male patients and those with good PS. Overall, the most severe symptoms included fatigue, muscle weakness, sleep disturbance, pain, drowsiness, numbness and bone aches during the induction period. Several sickness symptoms show a trend, although not statistically significant, of decrease during the first cycle of induction therapy. By the end of the first cycle of induction therapy, we observed significant increases in therapy induced symptoms which included numbness, muscle weakness, difficulty remembering, poor attention and diarrhea (all P

Description: Abstract 1396 Poster Board I-418 Introduction: Hematopoietic stem cell transplantation (HSCT) is an intensive therapy that may cure or control a variety of hematological malignancies. Although the toxicities associated with HSCT are well-described, patient report of symptom burden is rarely addressed. Lack of understanding of symptoms may result in failure to address symptoms and return patients to optimum functioning. Differences in the pattern of symptom burden between autologous (auto) and allogeneic (allo) HSCT and the special needs for symptom management that each type of therapy may require has not been addressed. The purpose of this study was to compare the symptom burden of patients undergoing allo- and auto-HSCT. Patients and Methods: Retrospective analysis of a combined data set of 155 patients from 3 longitudinal studies exploring the symptom burden of HSCT. Patients used modified versions of the M. D. Anderson Symptom Inventory (MDASI) to rate the severity of their symptoms (13 items) and the degree to which their symptoms interfered with daily living (6 items) on a 0–10 scale. Patients completed the MDASI at baseline, during conditioning therapy, on day of transplant, twice weekly for 4 weeks, and 1 to 2 times weekly for another 10 weeks. Symptom burden was measured as the area under the curve (AUC) of the mean MDASI symptom severity from baseline to 14 weeks post-HSCT. Results: Average age of the allo-HSCT patients was 52.9 years, whereas the auto-HSCT patients averaged 53.2 years. The allo- and auto-HSCT patients were 57% and 69% male, respectively, and 73% and 82% Caucasian, respectively. All allo-HSCT patients were being treated for acute myelogenous leukemia/myelodyspalastic syndrome; 66% of the auto-HSCT patients had multiple myeloma and 26% had non-Hodgkin's lymphoma. All allo-HSCT patients received short-course methotrexate as part of their graft-versus-host disease (GVHD) prophylaxis. Symptom severity peaked during the Week 1 post-HSCT for the auto-HSCT patients and Week 2 for the allo-HSCT patients. Three of the most severe symptoms experienced by both groups were lack of appetite, fatigue, and physical weakness. Other most severe symptoms experienced by the auto-HSCT patients were feeling physically sick and nausea. The other most severe symptoms reported by the allo-HSCT patients were pain and difficulty sleeping. Figure 1 shows the symptom burden of the 7 most severe symptoms combined for the two groups. Peak symptom severity was highest for the auto-HSCT group, but the overall AUC and symptom burden was greater for the allo-HSCT group because they remained more symptomatic throughout the 14 weeks of the study, whereas the auto-HSCT patients had returned to baseline levels by the end of 8 weeks. Although sore mouth was not one of the most severe symptoms, the auto-HSCT patients reported significantly more sore mouth during Week 1 post-HSCT (p ≤ 0.002), whereas the allo-HSCT patients reported significantly more sore mouth the second week (p ≤ 0.001). During Week 2, pain severity was significantly greater for the allo-HSCT patients than for the auto-HSCT patients (p ≤ 0.001), while diarrhea was significantly more severe for the auto-HSCT patients than for the allo-HSCT patients (p ≤ 0.001). Conclusions: Although patients undergoing auto-HSCT experience more severe acute symptoms from the conditioning regimen, they return to baseline symptom levels several weeks after HSCT. Allo-HSCT patients experience a slightly later peak in symptoms, mostly likely due to the effects of GVHD methotrexate prophylaxis, and continue to experience increased symptom burden up to 3 months post-HSCT, likely due to the development of GVHD and infection complications. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4920 Background: 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. Methods: 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. Results: 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

Description: Abstract 256 Background: Pain is not a symptom generally associated with thalassemia. However, healthcare providers have anecdotally noted increasing patient reports of chronic pain over the last decade creating an impetus for the TCRN to conduct this prospective, observational assessment of pain in patients with thalassemia over the age of 12. Study goals include assessment of pain prevalence, severity and sites and whether these factors are impacted by age, gender or diagnosis. Methods: Pain was assessed quarterly using the Brief Pain Inventory (BPI). Two hundred fifty-one thalassemia patients ranging in age from 12 to 71 (average age of 28.75) receiving care at one of 12 thalassemia centers across the US and Canada participated in the study. Fifty-four percent of participants were female. Diagnoses included: Beta Thalassemia (80%), E Beta thalassemia (11%), Hemoglobin H and H Constant Spring (6%) and other thalassemia conditions (3%). Eighty percent of participants were chronically transfused, 6% intermittently transfused and 14% had never been transfused. This report reviews baseline findings. Results: At study entry, 64% of the 251 participants reported experiencing pain over the last four weeks, of whom 21% reported pain on a daily basis. In comparison, 26% of the American public, 20 years and older, reported pain over a one month period according to National Center for Health Statistics data, 2006. Ordinal regression analysis of participant ratings of worst, least, and average pain over the last seven days demonstrated significant (p

Description: BACKGROUND: Most cancer patients with bone metastases report significant pain and substantial impairment in their ability to function. In particular, patients with MM are susceptible to bone pain because of bone damage. Patient-reported outcomes such as a general health outcome measure and a legacy pain instrument may provide valuable information in determining the impact of this condition. The goal of this study was to provide a descriptive profile of health status for cancer patients using the EQ-5D-3L (EQ-5D), a commonly used tool to measure health utility scores. Another goal is to evaluate the predictive information provided by the Brief Pain Inventory (BPI), a self-report pain assessment tool designed to capture pain severity and interference in patients. These information may be useful in estimating the health status of patients where the EQ-5D was not administered. METHODS: Data was pooled across three denosumab registrational trials '20050136', '20050103', and '20050244'. Patients completed the EQ-5D and the BPI at baseline. Eligible patients had histologically confirmed advanced cancers, radiographic evidence of at least one bone metastasis (or lytic bone lesion from multiple myeloma), ECOG of 2 or better and adequate organ function. Using data from patients with MM (N=168), descriptive statistics were used to present summary information on health-related quality of life states and utility scores. Linear regressions were used to examine how BPI severity and interference subscale scores relate with EQ-5D utility scores. Ordinal regressions were used to evaluate how well BPI items predict EQ-5D individual items. Bonferroni adjustments were made when evaluating the relationships of BPI items to individual EQ-5D items. These analyses were repeated using data across several groups of cancer patients to determine if similar results can be obtained (breast cancer, N=2,044, prostate cancer, N=1,819 and others, N=1,509). RESULTS: About 9% of MM patients reported perfect health compared with 11% of all cancer patients. Of the 5 dimensions measured by the EQ-5D, the MM cohort rated pain (80%) the highest with moderate to extreme problems. This was followed by usual activities (68%), mobility (63%), anxiety/depression (49%), and self-care (36%). Similar order was observed across all cancer groups, but with slightly lower percentages for most items: pain (78%), usual activities (58%), mobility (55%), anxiety/depression (57%), and self-care (26%). Although pain interference subscale score explained more of the variability in the EQ-5D utility scores compared with pain severity items in the MM cohort (39% vs 31%) and for all patients (41% vs 34%), model fit was less than ideal (mean squared error=0.23 - 0.25). Hence, BPI items were fitted into individual EQ-5D items. Ordinal regression models fitting BPI items into individual EQ-5D items for the MM cohort showed good predictive power as measured by the concordance index c for mobility (86%), self-care (80%), usual activities (83%), pain (90%) and anxiety/depression (78%). For all patients, similar model fit were obtained for mobility (83%), self-care (78%), usual activities (81%), pain (90%) and anxiety/depression (72%). Further examination of the ordinal regression models across all groups showed that three BPI pain severity items, 'pain at its worst', 'average pain' and 'pain now' in addition to interference with activity and interference with work significantly predicted the EQ-5D pain item. Five interference items, activity, walking ability, work, sleep and enjoyment of life significantly predicted the EQ-5D usual activities item. Finally, 'pain now' and four interference items, relationship with others, enjoyment of life, mood, and activity significantly predicted the EQ-5D anxiety/depression item. CONCLUSIONS: Patients with MM reported several functional limitations on the EQ-5D. Majority of the patients reported moderate to extreme problems in all EQ-5D dimensions except self-care. Model fit of ordinal regression models relating BPI items with EQ-5D items are reasonable underscoring the benefit of using the BPI for planning patient care and health status evaluation. This consistency was also found across cancer groups that primarily include breast and prostate. The resultant model demonstrates the significant contribution of pain severity and interference in determining health status in this patient population. Disclosures Mendoza: Amgen Inc.: Consultancy. Shi:Amgen Inc.: Consultancy. Ma:Amgen Inc.: Employment. Zhang:Amgen Inc.: Employment. Qian:Amgen Inc.: Employment. Cleeland:Amgen Inc.: Consultancy.

Description: Abstract 3838 Background: Symptom burden is the combined impact of symptoms from disease and treatment on daily functioning. Lack of symptom recognition may result in failure to address symptoms and maximize patient functioning. Patient-reported outcomes (PROs) can be endpoints in clinical trials to establish treatment benefits. The purposes of this study are to develop a short, easily understood, valid, and reliable patient questionnaire for measuring Philadelphia-chromosome-positive chronic myeloid leukemia (CML) symptom burden and to describe the symptom burden. This abstract reports preliminary results. Methods: The 13 core symptom items and 6 interference items of the M. D. Anderson Symptom Inventory (MDASI), rated on a 0-to-10 scale, are the base for the MDASI-CML. In addition, 6 CML-specific symptom items were generated from interviews with patients and the ratings of an expert panel. 160 patients with CML will complete the MDASI-CML every 2 weeks for one year using interactive voice response (IVR) technology. Information on performance status and quality of life will be collected every 3 months. Psychometric analyses will reduce the number of items to the optimal set describing symptom burden; determine predictive, construct, and concurrent validity; and establish internal consistency and test-retest reliability. The feasibility of collecting symptom data from this population of chronic disease patients using IVR technology will be assessed. The symptom burden of CML will be described through descriptive, correlational, cluster, and factor analyses. Results: As of June 30, 2010, data was available on 71 patients. Average age at study enrollment is 51.6 years, 62% are male, 97.2% are in the chronic phase of CML, 91.5% are receiving kinase inhibitor (KI) therapy, and all patients have a clinician-rated ECOG performance status of 1 or less. Four patients have dropped out of the study because of time required to complete assessments. 70.5% (249/353) of IVR calls have been completed as planned, and 66% of patients have responded to at least 80% of planned calls. The reliability index (Cronbach alpha) for the 13 core symptom items is 0.90, for the 6 CML-specific items is 0.75, and for the 6 interference items is 0.93. Thirty-five patients on KI therapy reported symptoms for at least 3 months. An exploratory analysis of the area under the curve of the most severe symptoms and interference for the 3 groups over the initial 3 months of the study is shown in Table 1. Fatigue was the most severe symptom reported by patients regardless of type of KI therapy. While the sample size is too small to determine significant differences, there is a trend toward lower symptom burden in nilotinib patients. Large effect sizes (〉0.5) were found between mean AUCs for fatigue, disturbed sleep, pain, muscle soreness and cramping, and swelling in nilotinib patients and both imatinib and dasatinib patients. In addition, there were large effect sizes between mean interference AUCs for work, walking, general activity, and mood in nilotinib patients and both imatinib and dasatinib patients. Implications: Collecting symptom assessments at regular intervals using an IVR system is feasible and useful in patients with CML receiving KI therapy, as patients may experience significant symptom burden, especially fatigue. Different KI drugs may influence the level of symptom burden. The results of this preliminary analysis warrant further investigation of the symptom burden of KI therapies. Data collection for this study is ongoing. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 677FN2 Background: It is well recognized that patients with multiple myeloma (MM) who undergo induction chemotherapy experience treatment-induced numbness and tingling, indicating the development of peripheral neuropathy (PN) that can be a dose-limiting side effect. There is need to identify which patients are more at risk for this side effect, to understand its association with the development of other symptoms, and to explore possible biomarkers associated with its development. Inflammation has been proposed as one mechanism underlying PN. Methods: Patients with MM who were scheduled to receive bortezomib-based chemotherapy with or without lenalidomide before evaluation for autologous stem cell transplantation were enrolled on study. Enrollment generally occurred before induction therapy, but no later than two cycles of induction. Patients with pre-existing PN were excluded, but patients with diabetes were not. Patients repeatedly rated numbness/tingling, pain, and other symptoms via the M. D. Anderson Symptom Inventory (MDASI) during induction therapy (twice a week for 12 weeks, then weekly up to 16 weeks). Patients contributed a serum sample before start of every chemotherapy cycle. A panel of cytokines was examined by Luminex method. Mixed regression analysis was used to describe the trajectory of numbness/tingling over time and to examine the relationship of numbness to other symptoms during this period. Group-based trajectory modeling was used to identify a group of patients who developed more-severe numbness during induction, to determine baseline risk factors for numbness development, and to compare serum cytokine profiles between high-numbness and low-numbness groups. Results: Sixty-four patients were enrolled. During induction, numbness/tingling persistently worsened from baseline (P=.011). A diagnosis of diabetes without PN (10/64) was the only baseline clinical predictor of high numbness development (P=.01). Increasing numbness over time was significantly associated with pain (P=.005), disturbed sleep (P