ALBERT

Description: Introduction: Multiple myeloma (MM) is a disease of aging. The prognosis of older adults with MM is influenced by the presence of geriatric syndromes, including dependence in daily activities and comorbidities. Falls, another common geriatric syndrome, are associated with greater risk for severe toxicity of chemotherapy and survival in older adults with solid tumors. Among older adults with MM, the prevalence of falls and factors predictive of falls are yet unknown. Thus, we sought to determine the prevalence of falls in a cohort of older adults with newly diagnosed MM and examine associations between falls and functional status, comorbidities and self-reported health. Methods: Using data from the linkage of the Surveillance, Epidemiology, and End Results (SEER) national cancer registry with the Medicare Health Outcomes Survey (MHOS), we identified unique patients with a diagnosis of MM in the SEER registry who participated in the MHOS survey, which includes individuals who are enrolled in Medicare Advantage organizations. An item inquiring about falls was present in the MHOS survey starting in 2006. For this analysis, participants (pts) were included if they completed the MHOS baseline survey within 1 year of their diagnosis of MM. Baseline characteristics were examined with descriptive statistics. Associations between falls and patient-reported data on function, comorbidities and self-rated health were examined using Student's t-test, Pearson Chi-square or Fisher's exact test, as appropriate. We identified 1327 unique patients, of whom 376 completed their baseline MHOS survey within 1 year of diagnosis. Of these, 190 provided responses to the item regarding falls and are included in this analysis. Results: The median age of the cohort was 77 years (range 47-97). The cohort was diverse, with 58.9% white race, 19.5% Asian/Pacific Islander, 11.6% Hispanic/Latino and 10.0% black race. Half (50.0%) were male, 48.4% female, and 1.6% unknown gender. Over one-quarter (25.2%) of pts reported a fall within the prior 12 months. Fallers were more likely to report a history of congestive heart failure than nonfallers (22.7% vs 7.9%, p=0.012); the remaining comorbidities examined (coronary artery disease, stroke, chronic obstructive pulmonary disease and diabetes) were not associated with falls. Of those who reported 2 or more weeks of depression in the past year, 41.4% reported a fall, compared with only 20.1% of those who did not report depression (p=0.004). Fallers were more likely to report limitations in moderate activities (81.2% vs 62.1%, p=0.015) and in climbing several flights of stairs (89.1% vs 64.9%, p=0.001). Pts who reported numbness in their feet some, most or all of the time were numerically but not statistically more likely to report a fall (35% vs 21.9%, p=0.070). Compared with nonfallers, fallers reported more days in the past 30 days when their physical health was not good (15.8 vs 10.0 days, p=0.024), more days in the past 30 days when their mental health was not good (10.7 days vs 4.1 days, p=0.002) and more days in the past 30 days when their health interfered with their daily activities (14.3 vs 7.0 days, p=0.001). Pts who had fallen were more likely to report that their health was fair or poor than those who had not fallen (67.4% vs 33.8%, p

Description: Introduction The incidence of multiple myeloma (MM) increases with age, yet some cytogenetic changes are actually more common in younger patients with MM (Avet-Loiseau J Clin Oncol 2013).  This suggests that a mechanism other than chromosomal changes underlies the increased incidence with age.  Senescent cells secrete a number of proinflammatory cytokines, chemokines, growth factors and proteases resulting in the senescence-associated secretory phenotype (SASP), which can promote tumor growth.  Preclinical data suggests that myeloma bone marrow stromal cells express the SASP (Andre PLOS ONE 2013). We hypothesized that SASP factors correlate with age in patients with MM. Methods Peripheral blood serum and matched bone marrow aspirate plasma from patients with multiple myeloma were evaluated for selected factors associated with the SASP using quantitative multiplex immunoassay (Rules Based Medicine, Austin TX USA).  SASP factors with a known role in MM [interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-15 (IL-15), granulocyte-macrophage colony-stimulating factor (GMCSF), intercellular adhesion molecule 1(ICAM1), osteoprotegerin (OPG), hepatocyte growth factor (HGF), insulin-like growth factor-binding protein(IGFBP-1), interleukin-1 beta (IL1b), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1 alpha(MIP-1a), angiogenin, leptin,  vascular endothelial growth factor receptor 1(VEGFR1) and stem cell factor(SCF)] were selected. The relationship between age and SASP factors were analyzed using Kendall tau rank correlation coefficient. Results Samples from 25 patients (each with peripheral blood serum and matched bone marrow aspirate plasma) were analyzed.  The median age was 62 (range 47 - 74). Disease states were as follows: 36% newly diagnosed/untreated, 24% pretransplant and 40% relapsed.  ISS stage included 40% stage I, 28% stage II and 32% stage III.  Three of the selected SASP factors in the peripheral blood correlated   with age:  IL-8 (Kendall Tau 0.334, p=0.027), OPG (Kendall Tau 0.289, p=0.046) and MCP-1 (Kendall Tau 0.332, p=0.022).  No SASP factors tested in the bone marrow plasma were significantly correlated with age. Conclusions We demonstrated age-associated differences in the SASP factors IL-8, OPG and MCP-1 in the peripheral blood of myeloma patients.  Future research will examine differences between patients with myeloma and age-matched controls without cancer. Disclosures: Vij: Celgene : Honoraria, Research Funding, Speakers Bureau; Millennium: Honoraria, Speakers Bureau; Onyx: Honoraria, Research Funding, Speakers Bureau. Stockerl-Goldstein:Celgene : Speakers Bureau; Celgene : Speakers Bureau; Millennium: Speakers Bureau; Millennium: Speakers Bureau.

Description: Background: Over the past two decades, peripheral blood stem cells (PBSC) have surpassed bone marrow as the preferred graft source for adult allogeneic transplantation due to its more rapid engraftment and potentially better graft-vs-tumor effects, and because PBSC collection is much less invasive for the donor. The optimal CD34+ PBSC dose is ≥ 4.0x106cells/kg, but doses ≥ 8.0x106cells/kg are suggested by some for reduced-intensity conditioning and haploidentical transplants. There is no established minimum CD34+ PBSC dose, but doses below 2.0x106cells/kg have been associated with a higher risk of engraftment delay and failure. There is significant inter-donor variability in the ability to mobilize PBSCs. Several factors have been identified as predictors of PBSC mobilization in healthy donors including: gender, age, weight, body mass index (BMI), and blood counts before and after mobilization. The impact of the donor’s comorbidities on mobilization is currently unknown. Patients/Methods: We performed retrospective chart review of 488 consecutive adult patients who underwent apheresis for allogeneic stem cell donation at Washington University School of Medicine from 2006 through 2013. Patients who received any collection regimen other than 10mcg/kg of G-CSF daily with 20 liters (+/-10%) apheresis on Day 5 were excluded. Patients who had undergone a previous apheresis for stem cell donation were excluded. Univariate analysis was performed to identify predictors of CD34+ PBSC collection in a single apheresis. Variables analyzed were: gender; age; weight; BMI; donor-to-recipient weight ratio; pre and post-mobilization blood counts (white blood count [WBC], hematocrit, platelets, neutrophils, lymphocytes, and monocytes); pre-mobilization glucose and triglyceride levels; post-mobilization peripheral blood (PB) CD34+count; and medical history significant for hypertension, hyperlipidemia, or diabetes mellitus. Subsequently, a linear regression multivariate analysis was performed with all variables found to be significant in the univariate analysis. 2-tailed tests for significance were used throughout the analysis. Results: 304 patients met the eligibility criteria for analysis. The median age was 53 years (range 18-76), 90% were Caucasian, and 50% were male. The median number of CD34+ cells collected was 7.4 x106/kg (range 0.8-27.1). 97% (295) collected ≥ 2.0x106 CD34+cells/kg, 81% (247) collected ≥ 4.0x106 CD34+cells/kg, and 44% (134) collected ≥ 8.0x106 CD34+ cells/kg. Post-mobilization PB CD34+ count (r= 0.841, p

Description: Introduction: Survival rates continue to improve after allogeneic HCT (Gooley et al, NEJM, 2013). Population-based studies also indicate overall improvement in survival of older (60-80 years old) AML patients (pts) (Bower, Blood Cancer Journal, 2016). Yet, only a small minority (6%-8%) of them receive HCT (Medeiros, Ann Hematol. 2015). Given these potentially incongruent findings and the changing face of survival in AML, we designed the first prospective multi-center longitudinal study dating from first presentation of adults with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We compared survival according to whether or not pts received HCT at later time points. Methods: We enrolled 695 pts (Table 1). Data on demographics, AML status, cytogenetic risks per European Leukemia Network (ELN), and response; age; comorbidities per the HCT-comorbidity index (CI); function including activities of daily living (ADL); frailty; geriatric assessment including cognition; QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale, ENRICHD Social Support Instrument, Social Activity Log, and Patient Health Questionnaire 9-item Depression Scale (PHQ-9) were collected at enrollment and at 1, 3, 6, 9, 12, 18, and 24 months thereafter. We used time-dependent Cox regression analyses to identify baseline and time-dependent risk factors associated with mortality in the overall population. The factors identified as significantly associated with mortality (p

Description: Background: Black patients with multiple myeloma (MM) have poorer outcomes than their white counterparts. This has largely been attributed to reduced access to health care; however, little data exists comparing the disease and overall health status at MM presentation between the two races. More severe disease burden, symptom burden, or comorbidities could also explain the differences in outcome. Objective: To compare disease burden, symptom burden, and comorbidities between black and white patients with MM. Methods: Two datasets were analyzed: 1) the Multiple Myeloma Research Foundation (MMRF) CoMMpass study interim analysis 6, and 2) the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) 2015 dataset (SEER years 1973-2011; MHOS years 1998-2013). The CoMMpass dataset included 625 patients who completed the EORTC QLQ-C30 and QLQ-MY20 at MM diagnosis. The SEER-MHOS dataset included 377 patients who completed the HOS survey the year of or year prior to MM diagnosis. All patients identified as a race other than white or black/African American were excluded. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with the Mann-Whitney U test. Results: CoMMpass: 585 patients were eligible for analysis. 477 (82%) were white, 108 (19%) were black. Whites and blacks were similar in median age, but a significantly higher percentage of white patients were female (p=0.027). Overall, black patients were more likely to be stage III (p=0.041), have higher LDH (p=0.006) and creatinine (p=0.001), and lower hemoglobin (p

Description: Background: The clinical presentation of multiple myeloma (MM) varies greatly but often includes bone pain, anemia, renal dysfunction, hypercalcaemia, and/or constitutional symptoms. There are no signs or symptoms that are disease specific. The earliest staging system for MM, the Durie-Salmon (DS), associated disease and symptom burden with prognosis; however, it has been largely replaced by the International Staging System (ISS), which is easier to compute and better identifies patients with the poorest prognosis. It is unclear if ISS stage, like DS, is associated with disease or symptom burden. Objective: To compare disease and symptom burden of patients with newly diagnosed MM by ISS Stage. Methods: Data was extracted from the open-access Multiple Myeloma Research Foundation (MMRF) Researcher Gateway corresponding with interim analysis 6 from the CoMMpass study. The CoMMpass study is enrolling 1000 newly diagnosed MM patients who will be tracked longitudinally for 5 years. CoMMpass collects relevant clinical data and patient reported quality of life (EORTC QLQ-C30 and QLQ-MY20), as well as sequential tissue samples. Eligibility requirements for CoMMpass include: symptomatic MM with measureable disease by SPEP (≥1.0g/dL), UPEP (≥200mg/24 hours), or SFLC (≥10mg/dL); receiving an immunomodulator and/or a proteasome inhibitor for initial MM treatment; and no prior malignancies in the past 5 years. All clinical data was reported by trained data analysts at the enrolling center with the exception of flow cytometry which was performed centrally; raw lab values for beta-2 microglobulin and albumin were entered and stage was subsequently calculated by the analysts for this study according to the ISS (Greipp et al, JCO 2005). Twenty-six patients with unknown ISS were excluded from the analysis. Data was analyzed using SPSS 21. Categorical variables were compared using χ2, continuous with one-way ANOVA tests. Results: 599 patients were eligible for analysis. Sex, race, and heavy and light chain isotypes were all evenly distributed among the ISS stages; however, median age for ISS stage III was 67, 65 for stage II and 62 for stage I (p

Description: Background: The need to repeat peripheral blood stem cell (PBSC) mobilization and collection arises infrequently in healthy donors, but may be required due to insufficient initial collection, graft failure, or relapse of the recipient’s disease. Currently no published data exists on the efficacy of remobilization of healthy PBSC donors. Studies of remobilization in patients undergoing autologous transplantation (ASCT) have largely focused on the use of alternative mobilization agents such as chemotherapy or plerixafor. Boeve et al (Bone Marrow Transplant, 2004) reported that remobilization with G-CSF in patients undergoing ASCT who failed initial mobilization with G-CSF, resulted in higher numbers of CD34+ cells collected than the initial collection, though this required a doubling of the dose of G-CSF. Patients/Methods: We performed retrospective chart review of 977 consecutive adult (〉18 yrs) donors who underwent apheresis for PBSC donation at Washington University School of Medicine from 1995 through 2013. We identified 66 donors who had undergone more than one mobilization. Two cohorts of donors were identified for analysis: Group 1 included donors mobilized initially and again subsequently with G-CSF (10 ug/kg/day), or GM-CSF (5 ug/kg/day) + G-CSF (10 ug/kg/day). Group 2 consisted of donors mobilized with a CXCR4 antagonist, plerixafor (240-320 ug/kg) or POL6326 (1000-2500 ug/kg), and subsequently were remobilized with G-CSF (10 ug/kg/day). Statistical Analysis: Spearman correlations were performed to analyze the relationship between peak peripheral blood (PB) CD34+/uL level; the number of CD34+ cells collected per kg (recipient weight); and the number of CD34+ cells per L of apheresis collected during initial mobilization (MOB1) and remobilization (MOB2); and the interval (days) between MOB1 and MOB2. One-way ANOVA with repeated measures analyses were performed to determine the relationship of PB CD34+/uL, CD34+/kg and CD34+/L during MOB1 and MOB2. Results: Group 1 included 30 donors. The median age was 49 years (range 18-75) and 15 were male. The median number of days between MOB1 and MOB2 was 140 (range 26-2238). All 30 donors were remobilized due to graft failure or relapse of the recipient’s disease. PB CD34+/uL, CD34+/kg and CD34+/L all correlated between MOB1 and MOB2. The mean PB CD34/uL at MOB1 was 69 compared to 37 at MOB2 (p= 0.029); the mean CD34/kg collected at MOB1 was 5.6x106 compared to 3.3x106 at MOB2 (p= 0.002); and the mean CD34/L collected at MOB1 was 24.0x106 compared to 17.6x106at MOB2 (p= 0.023). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 1. Group 2 included 32 donors. The median age was 51 years (range 21-67) and 18 were male. The median number of days between MOB1 and MOB2 was 20 (range 4-1123). 18 donors were remobilized due to mobilization failure, while 14 were remobilized due to graft failure or relapse of the recipient’s disease. The mean PB CD34/uL at MOB1 was 15 compared to 68 at MOB2 (p〈 0.001); the mean CD34/kg collected at MOB1 was 2.5x106 compared to 7.1x106 at MOB2 (p〈 0.001); and the mean CD34/L collected at MOB1 was 10.6x106 compared to 30.1x106at MOB2 (p〈 0.001). The interval between MOB1 and MOB2 did not correlate with any of the MOB2 variables. Results from the analysis are summarized in Table 2. Conclusion: Remobilization with G-CSF or GM-CSF and G-CSF after initial successful mobilization with the same regimen results in poorer mobilization while remobilization with G-CSF after initial mobilization with a CXCR4 antagonist results in dramatically improved mobilization. The reason for this remains unclear, but in this study the interval between collections was not associated with successful remobilization. Abstract 850. Table 1 Group 1 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 69 (13-417) 37 (1-115) F(1.0, 29.0) = 5.26, p= 0.029 r= 0.615, p〈 0.001 CD34/kg (x106) 5.6 (0.8-13.8) 3.3 (0.3-10.6) F(1.0, 29.0) = 11.77, p= 0.002 r= 0.483, p= 0.007 CD34/L (x106) 24.0 (4.5-72.0) 17.6 (2.8-41.3) F(1.0, 29.0) = 5.74, p= 0.023 r= 0.566, p〈 0.001 Abstract 850. Table 2 Group 2 MOB 1 MOB 2 One-way ANOVA Spearman Correlation PB CD34/ul 15 (2-54) 68 (14-358) F(1.0, 31.0) = 23.16, p〈 0.001 r= 0.433, p= 0.013 CD34/kg (x106) 2.5 (0.2-19.7) 7.1 (1.7-42.4) F(1.0, 31.0) = 33.84, p〈 0.001 r= 0.769, p〈 0.001 CD34/L (x106) 10.6 (1.4-67.1) 30.1 (6.0-165.0) F(1.0, 31.0) = 34.70, p〈 0.001 r= 0.774, p〈 0.001 Disclosures No relevant conflicts of interest to declare.

Description: Background: Bone lesions and extramedullary plasmacytomas, present in ~70% and ~15% of multiple myeloma (MM) patients at diagnosis, respectively, are a major source of morbidity. Extensive bone or extramedullary disease is often associated with severe pain, fracture, or spinal cord compression requiring immediate medical attention. Palliative radiation to the afflicted area(s) can provide relief or reduction of the associated symptoms. The presence of bone lesions or extramedullary plasmacytomas at MM diagnosis have been linked to poorer prognosis, but to date, the prognosis of patients with extensive bone or extramedullary disease requiring radiotherapy during front-line treatment is unclear. In a single institution retrospective study of 162 newly diagnosed MM patient’s, including 87 who received front-line radiotherapy, Yaneva, et al (J Buon, 2006) found no survival difference between patients who received radiotherapy during front-line treatment and those who did not. Methods: Using the SEERStat software, we extracted the case listings of 85,115 patients diagnosed with MM from 1973 through 2010 in Surveillance Epidemiology and End Results (SEER)-18 registries database based on the November 2012 submission. Children (under 18 years old) were excluded. Autopsy or death certificate only cases were excluded. As non-black minorities have been historically underrepresented in the SEER databases, patients identified as any race other than white or black were excluded. Patients were followed for OS through December 2011. Disease-specific-survival was defined as death from myeloma. Patients were classified as having radiotherapy during front-line treatment or not. Patients who refused radiotherapy (n = 184) or for whom radiotherapy status was unknown (n = 973) were excluded. Results: 77,714 patients were eligible for analysis. The median age at diagnosis was 70 years (range 18-85+); 54% were male; 19% were black. The median follow-up was 22 months (range 0-441). 25% (n = 19,295) of patients received radiotherapy during front-line treatment. Radiotherapy during front-line treatment was more common among patients under the age of 60 at diagnosis (30.9% vs 21.4%; p 〈 0.001), white patients (25.5% vs 21.8%; p 〈 0.001), and male patients (26.2% vs 23.2%; p 〈 0.001). The frequency of radiotherapy during front-line treatment decreased in the most recent decade (22.8% vs 27.3%; p 〈 0.001). Patients who received radiotherapy during front-line treatment had an estimated median disease-specific-survival of 38 months compared to 46 months for patients without (p 〈 0.001). In a multivariate cox regression model of age, race, sex, and radiotherapy during front-line treatment, all four variables were independently significant (Table 1). Radiotherapy was associated with a 17% (95% CI 15-20) increase in disease-specific mortality. The impact of radiotherapy was relatively stable over the time frame studied (Table 2). Conclusions: Radiotherapy during front-line treatment, a surrogate for extensive bone or extramedullary disease at MM diagnosis, is independently associated with increased disease-specific mortality. It has remained a relatively stable predictor of poorer prognosis throughout the timeframe tested, suggesting that MM treatment advances have not overcome the poor prognosis associated with extensive bone lesions or extramedullary disease at MM diagnosis. Table 1 Multivariate Overall Survival Analysis Overall Age HR1 (95% CI) p value

Description: Background: The use of autologous stem cell transplants (ASCT) for multiple myeloma (MM) has greatly improved overall survival (OS), however, not all patients have benefited equally. Several studies have indicated that patients over the age of 65 or 70 at diagnosis had no immediate improvement in OS following the use of ASCT for MM, which is intuitive as ASCT was not covered by Medicare until 2001 and today is still often reserved for patients under 70. In addition, Waxman, et al (Blood, 2010) reported that ASCT for MM, resulted in nearly a two-fold improvement in OS in white patients compared to black patients. This suggests that white patients had better access to ASCT as retrospective studies of MM patients who undergo ASCT have failed to show an OS difference between the two races. Disparities in the OS benefit of ASCT among patients of different socioeconomic groups have not been reported on to date. It is also unclear if these disproportional improvements in outcomes have continued following the approvals of bortezomib and lenalidomide. Methods: Using the SEERStat software, we extracted the case listings of 85,115 patients diagnosed with MM from 1973 through 2010 in Surveillance Epidemiology and End Results (SEER)-18 registries database based on the November 2012 submission. Children (under 18 years old) were excluded. Autopsy or death certificate only cases were excluded. Patients identified as any race other than white or black were excluded. Patients were followed for OS through December 2011. Patients were divided into three cohorts based on the year of diagnosis, era 1 those diagnosed from 1973 to 1994, era 2 those diagnosed from 1995-2002 (to coincide with ASCT), and era 3 those diagnosed from 2003-2010 (to coincide with bortezomib’s approval). Socioeconomic status (SES) was approximated by median household income (MHI) of each patient’s county of residence from the 1990 US census; patients were divided into tertiles within their era of diagnosis based on MHI and classified as low-SES, middle-SES, or high-SES. Results: 78,681 patients were eligible for analysis. The median age at diagnosis was 70 years (range 18-85+); 54% were male; 18% were black. The median follow-up was 22 months (range 0-441). The OS of white patients increased from 23 months in the era 1 to 27 months in era 2, to 36 months in the era 3 (p