ALBERT

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: Patients who undergo allogeneic BMT experience a rapid increase in multiple symptoms, including pain, fatigue, poor appetite, drowsiness, dry mouth, and disturbed sleep, from pre-BMT to nadir of white blood cell count. The objective of this study was to prospectively evaluate baseline levels of serum inflammatory cytokines and other factors related to symptom development from pre-BMT to nadir. Methods: Repeated multiple-symptom assessments with the M. D. Anderson Symptom Inventory (MDASI) were completed for 30 patients with AML/MDS at day of hospital admission (baseline), day of conditioning, day of BMT, day of nadir, and day 11 of BMT. A panel of serum inflammatory cytokines (IL-1ra, IL-6, IL-8, IL-10, IL-12, TNF-a) was assayed at baseline, conditioning, day of BMT, day after BMT, and at nadir. Results: Patients self reported multiple symptoms that peaked 3 days after nadir. We adjusted for potential confounding factors, including age, sex, race, disease status pre-BMT, infusion dose of CD34+, and conditioning regimen, that could have affected symptom outcomes in the mixed effect models for symptom severity. Race was the only significant factor affecting the severity of the baseline symptom cluster (pain, fatigue, poor appetite, disturbed sleep, drowsiness, and dry mouth) and the change in symptom severity from baseline to peak (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 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

Description: Objectives: In cancer patients undergoing intensive therapy such as stem cell transplant, functional recovery is an important but challenging outcome to measure. This prospective, longitudinal study aimed to demonstrate how a patient-reported outcome (PRO) could predict patient-performed testing (PPT) for measuring functional impairment after autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM). Methods: A secondary analysis was conducted using data from a randomized controlled trial of 2 stem cell doses for MM patients undergoing ASCT. Symptom interference on walking (a PRO) was measured by the MD Anderson Symptom Inventory (MDASI), on a 0-10 scale, with a higher score referring to a greater interference. The PPT outcome was assessed via distance walked on the six-minute walk test (6MWT). MDASI and 6MWT were administrated before ASCT, and on days 0, 3, 5, 7, 14, 21 and 28 from ASCT. Mixed effects modeling was used to examine 1) the longitudinal relationship between MDASI-walking symptom interference score and 6MWT walking distance and 2) the MDASI-walking symptom interference scores between patients who completed 6WMT and those who did complete the test. Results: Seventy-nine patients were included in the study. Of note, no significant clinical, functional or symptom differences were detected between the 2 doses of stem cells (Shah et al, BBMT 2015); thus the entire study population was considered in the same cohort. The average pre-ASCT walking distance was 452±185 feet and MDASI-walking score was 2.1±2.6. From day of transplant, the 6MWT decreased until day 5 (329±140, P=0.04, compared to pre-ASCT) and then recovered to pre-ASCT level at day 28 (408±131, p=0.176, compared to pre-ASCT). MDASI-walking interference symptom score worsened until day 7 (4.7±3.2, P

Description: Abstract 603 Background and Objectives: Cancer or aggressive cancer therapy induced cognitive dysfunction is receiving increased attention as a survivorship issue due to its potential to impact occupational, social, and scholastic activities. Neuropsychological functioning has been investigated previously in patients with hematological malignancies undergoing Autologous Hematopoietic Stem Cell Transplantation (AuHSCT); however, only a couple of studies have had samples that included patients specifically with multiple myeloma (MM). The objectives of this study were to: 1) report the incidence of cognitive deficits in patients with MM post-induction (pre- AuHSCT) and post-AuHSCT; 2) present changes in deficits based on patients' performance on a battery of key cognitive tests 1 month and 3 months post-AuHSCT; 3) identify sub-groups of patients that may be vulnerable to cognitive decline, and 4) present a comparative evaluation of patient's objective performance with their subjective self-appraisal of cognitive function pre- and post-AuHSCT. Methods: Patients were recruited from the University of Texas MD Anderson Cancer Center, Houston, Texas if they: 1) had a confirmed diagnosis of MM; 2) were ≥ 18 years old, and 3) had received induction therapy and been approved to receive AuHSCT. Neuropsychological tests designed to measure multiple cognitive domains were administered pre-AuHSCT and at 1 and 3 months post-AuHSCT. Tests included the evaluation of attention, psychomotor speed, learning and memory, language, and executive function. Patients' symptoms were assessed using the MD Anderson Symptom Inventory Multiple Myeloma Module (MDASI-MM). Results: Approximately 46% of patients exhibited cognitive impairment post induction (pre-AuHSCT) (n =48), 37.8% at 1 month post-AuHSCT (n =37), and 32.4% at 3 months post-AuHSCT (n = 34). Pre-AuHSCT, impairments were higher in learning and memory, language, and executive function relative to other domains. Older patients, minorities, those with less education, and those with more comorbidities were significantly more likely to have cognitive deficits (all P's

Description: Abstract 1393 Poster Board I-415 Chronic lymphocytic leukemia (CLL) is the most prevalent form of adult leukemia. Patients with CLL have a long life expectancy and little attention has been paid to the symptom burden that accompanies this disease. We, therefore, wanted to explore the reliability and validity of the M. D. Anderson Symptom Inventory (MDASI) in measuring the symptom burden of patients with CLL. The MDASI is an established, reliable and validated tool for assessing cancer-related symptoms regardless of therapy or specific cancer diagnosis.1 The MDASI measures the most common symptoms across most cancer types and treatments: 13 items assess symptom severity at its worst in the last 24 hours and 6 items assess symptom-related interference in the last 24 hours, all rated on a 0–10 numeric scale. These 19 symptom and interference items comprise the “core” MDASI. We enrolled 126 consecutive patients with CLL being followed at our outpatient center. Patients eligible for this study were required to be speak English and have a pathological diagnosis of CLL. A clinical nurse conducted interviews, had patients complete self-administered MDASI, and collected information from patients' medical record. Sixty-three % of the patients were male, 95% were white non-Hispanic, the mean age was 59 years (range 29-79) with 27% of them age 65 years or older. Eighty-three % of the patients had Rai stage 0-2, and 56% were untreated. Factor analysis of the MDASI items resulted in a three-factor solution (physical symptoms, psychological symptoms, and gastrointestinal symptoms), which satisfied criteria for interpretability and model fit in a confirmatory setting. Cronbach coefficient alphas for the MDASI were 0.89 for the symptom severity subscale and 0.94 for the interference subscale. Convergent validity showed that the two MDASI subscales were significantly correlated with similar subscales of the SF-12 (12-Item Short-Form Health Survey). The most severe patient-reported MDASI symptoms were fatigue, disturbed sleep, drowsiness, distress, and difficulty remembering. Patients with poorer performance status (ECOG PS 2 vs. 1 vs. 0) reported significantly higher severity for both core MDASI and total interferences (all P 〈 .001). Patients with higher Rai staging [3-4 vs 0-2] reported significantly higher severity on core symptoms and interferences (P

Description: Symptom burden is the combined impact of all disease-related and therapy-related symptoms on one’s ability to function as one did before onset of disease or therapy. Lack of understanding of symptoms may result in failure to address symptoms and return patients to optimum functioning. This is critical for patients with chronic diseases who are receiving continuing therapy, such as patients with chronic myeloid leukemia (CML). Additionally patient-reported outcome measures are becoming primary endpoints in clinical trials to test results such as reduction in symptom burden that establish treatment benefits from the patient’s perspective. No patient-reported outcome measure for CML currently exists, and there is little understanding or knowledge of the symptom burden of CML and its treatment. The purpose of this study was to initially explore the symptom burden of CML. Methods: Retrospective analysis of 29 patients with CML who participated in two larger cross-sectional studies exploring cancer-related symptoms. Patients used 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. Results: Patient/treatment characteristics are summarized in Table 1. Table 1: Patient/Treatment Characteristics N=29 Mean SD Age 53.9 14.6 Highest Grade Completed 14.45 2.08 n % Sex–Male 17 58.6% Race–White, non-Hispanic 27 93.1% Employment Status–Employed or Homemaker 13 44.8% ECOG Performance Status–〈 2 21 72.4% Treatment Type Interferon-Based Therapy 9 31.0% Tyrosine Kinase Inhibitor 10 34.5% Mean global symptom severity was 1.86 (SD 1.76) and mean global interference was 1.79 (SD 2.05). Cronbach alpha for the symptom scores was 0.916 and for the interference scores was 0.922, indicating that the MDASI is reliable in this sample. The 6 most severe symptoms (mean severity score 〉 2.5) were fatigue, drowsiness, lack of appetite, disturbed sleep, difficulty remembering things, and dry mouth. Symptoms interfered most with work and general activities. Mean symptom severity scores and standard deviations for the top most severe symptoms and most bothersome interference items are reported in Table 2. Table 2: Symptom and Interference Means and SD There was no significant difference in mean symptom severity or interference between patients receiving interferon-based therapies and patients receiving tyrosine kinase inhibitors. There were significant differences in mean symptom severity (p = .001) and interference (p 〈 .001) scores between patients with good (0 or 1) and poor (≥ 2) ECOG performance status. Preliminary analysis has encouraged us to investigate further relationships among the 13 symptom items, the 6 interference items, and demographic, disease, and treatment related factors. This further, more-detailed analysis will be presented. n Minimum Maximum Mean SD Symptom Item Fatigue 29 0 9 4.62 2.691 Drowsiness 29 0 10 3.00 3.151 Lack of Appetite 29 0 8 2.83 2.916 Sleep disturbance 29 0 10 2.66 2.595 Difficulty Remembering 29 0 7 2.62 2.162 Dry mouth 29 0 10 2.52 2.681 Interference Item Work 28 0 9 3.14 3.003 Activity 28 0 10 3.11 2.897 Conclusion: Methods for patients with CML to report symptom burden to clinicians and researchers are needed. Based on preliminary results, the MDASI is a reliable instrument that captures many symptoms of CML and differentiates between levels of severity of illness. Further work is ongoing to identify and add symptom items to the MDASI that will capture CML-specific and treatment-specific symptoms.