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: CD34+-selected peripheral blood stem cell infusions without conditioning have recently been utilized for poor graft function (PGF) with promising results. Unfortunately, many patients have been unable to receive the boost infusion as their donors were unwilling or unable to undergo an additional stem cell collection. Therefore, we conducted this pilot trial utilizing either fresh or cryopreserved peripheral blood stem cell products to create CD34+-selected peripheral blood stem cell infusions for the treatment of PGF. Additionally, to explore relationship of CD34+ dose and response we included a cohort of donors mobilized with plerixafor in addition to the standard G-CSF. Methods: Poor graft function (PGF) was defined as ANC 〈 0.5k/μL, platelets 〈 30k/μL, or platelet or RBC transfusion dependence despite full donor chimerism and in the absence of GVHD more than 60 days following allogeneic stem cell transplant (allo-SCT). Three different donor products were used for CD34+ selection: (1) fresh mobilized product using G-CSF only (SC at a dose of 10 μg/kg daily for 5 days), (2) fresh mobilized products using G-CSF (SC at a dose of 10 μg/kg daily for 5 days, days-4 through day 0) and plerixafor (IV at a dose of 320 μg/kg on day 0), and (3) cryopreserved cells mobilized with G-CSF (SC at a dose of 10 μg/kg daily for 5 days). Seventeen donor-recipient pairs were enrolled onto this prospective study. The original allo-SCT donor either underwent an additional peripheral blood stem cell (PBSC) mobilization and collection with G-CSF only (n=5) or G-CSF plus plerixafor (n=9) or a cryopreserved product (n=3) from a previous collection (using G-CSF only) was used to create the CD34+ cells for infusion. CD34+ cell selection was performed using a CliniMACS. The infusion was not preceded by administration of any chemotherapy or conditioning regimen. Neutrophil improvement was defined as neutrophil count 〉 500/μl without growth factor support for 〉7 days; platelet improvement was defined as platelet count ≥ 50,000/µl without platelet transfusion support for 〉 7 days; and RBC improvement was defined as hemoglobin 〉 9 g/dL and transfusion independence. Complete response was defined as improvement of all involved cells lines; partial response was defined as improvement of platelets and/or neutrophils with continuing RBC transfusion dependence. Results: The mean post-selection CD34+ count per kg of recipient weight was 3.7x106, 12x106, and 1.7x106 for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively. Mean CD34+ yields (defined as the number of CD34+ cells after selection/CD34+ cells prior to CD34 selection) was 58%, 67%, and 31% for G-CSF only, G-CSF plus plerixafor, and cryopreserved products, respectively (Table 1 and Figure 1). The mean number of CD3+ T cells/kg infused in each product was 0.004 x 106, 0.032 x 106, and 0.015 x 106 for G-CSF only, G-CSF plus plerixafore and cryopreserved groups respectively (Table 1). Following the CD34+-selected stem cell infusion, 12 of the 17 recipients (71%) had a complete response including all 3 who received cryopreserved products; 3 had a partial response (17%) and 2 patients (12%) did not respond. One year relapse-free and overall survival was 71% and 65%. There was no treatment related toxicity reported other than graft-versus-host-disease (GVHD); three (18%) developed acute GVHD (1 grade I localized to the skin, 2 grade II with gut involvement), 6 chronic GVHD (2 limited and 4 extensive) (Table 1). Conclusion: Cryopreserved products seem to be a viable alternative to create CD34+ -selected peripheral blood stem cell infusions for the treatment of PGF. When collecting fresh products is an option, the addition of plerixafor increases CD34+ yield over G-CSF alone. Disclosures Abboud: Teva Phamaceutical: Research Funding. Uy:Novartis: Research Funding.

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: Performance Status (PS) is often used to assess the functional status of cancer patients. One of the most commonly used scales is the Eastern Cooperative Oncology Group (ECOG) PS. Using the ECOG PS scale, the oncologist assigns a score ranging from 0 (Fully active, able to carry on all pre-disease performance without restriction) to 4 (completely disabled; cannot carry on any selfcare; totally confined to bed or chair). In multiple myeloma (MM), a PS 〉 2 has been associated with a 35% increased risk of death following autologous stem cell transplant (ASCT) (Turesson et al, Br J Haematol, 1999), and therefore a PS ≤ 2 is generally required for ASCT and for eligibility in clinical trials. PS is often seen as a surrogate for health-related quality of life (HRQOL), which are patient reported measure(s) of well-being; however, they are separate constructs. While poorer PS has been associated with a decrease in HRQOL, it is unclear how much of the variance in HRQOL is explained by PS. Objectives: 1) To determine the association between PS and HRQOL; 2) to determine how much variance in HRQOL is explained by PS. 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 dataset included 562 patients who completed the EORTC QLQ-C30 and EORTC QLQ-MY20 at MM diagnosis. The range of scores for these HRQOL measures is 0-100, with higher scores indicating higher values. Data was analyzed using SPSS 21. The association between PS and HRQOL was assessed by one-way ANOVA tests; the amount of variance in HRQOL explained by PS was assessed by linear regression modeling. Results: PS was associated with all 9 HRQOL scales analyzed (p

Description: Background: Multiple myeloma (MM) is a disease of older adults, with a median age of diagnosis in the late 60s. While treatment advances have prolonged overall survival (OS) in MM, improvements have been modest among older MM patients. Symptom burden and quality of life are concerns for older patients, as they are more susceptible to treatment intolerance and dose reduction or treatment cessation. Older patients are often under-represented in clinical trials, and less information is available regarding their presenting clinical characteristics and treatment course. The Multiple Myeloma Research Foundation (MMRF) CoMMpass study, is a multicenter study in newly diagnosed multiple myeloma. It collects clinical-molecular data and patient reported health-related quality of life measures (EORTC QLQ-C30 and EORTC QLQ-MY20). In this study, we analyzed data from the CoMMpass study and compared presenting clinical characteristics, symptom burden and genetic features of newly diagnosed MM patients ≥ 75 years of age and those 〈 75 years of age. An additional analysis of t(4;14) was performed among those aged 75 years to confirm prior observations that the incidence of t(4;14) decreases with age (Avet-Loiseau et al. 2013). Methods: Clinical data from the interim analysis 6 of the CoMMpass study was extracted via the MMRF Researcher Gateway. CoMMpass eligibility requirements 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.Enrollment began in July 2011. Clinical data is recorded at enrolling centers by data analysts. Analysis was with STATA 12.0. Categorical variables were compared withχ2; continuous variables were compared with student's t-tests and Wilcoxon rank-sum tests. Results: 625 patients were eligible for analysis. 92 patients were ≥ 75 years of age, and 533 were 〈 75 years of age. Median ages were 80 years (range 75-93) and 63 years (range 27-74). Distribution of sex and race were evenly divided. Older patients had higher rates of International staging system (ISS), stage III disease at presentation. Baseline measurements of creatinine, platelet counts and hemoglobin were worse for older patients. On symptom and quality of life assessment, older patients were more likely to have difficulties with physical functioning, and were less likely to have difficulties with emotional functioning or finances. Subset analysis of those aged 〈 65 years, 65-75 years and 〉 75 years showed a trend towards decreasing rates of t(4;14).Results are summarized in Table 1. Conclusion: Older patients in this study had higher ISS stage at diagnosis and worse ECOG performance status scores. Baseline labs showed inferior renal function and lower platelet and hemoglobin levels. Emotional and financial status was rated higher than younger patients, while physical functioning was worse. A trend towards decreased incidence of t(4;14) was appreciated by age. Table 1. Clinical Characteristics ≥ 75 years (n=92) 〈 75 years (n=533) P Demographics Median age in years 80 63 Sex % NS Male 63 60 Female 37 40 Race % NS White 81 79 Black 19 18 Other 0 3 Heavy Chain % NS IgG 83 77 IgA 17 23 Light Chain % NS Kappa 65 62 Lambda 33 37 Biclonal 2 1 Disease Burden ISS Stage % 75 years 65-75 years

Description: Background: Tbo-filgrastim, biosimilar to filgrastim, was approved by the FDA in 2012 as a new drug due to the lack of a biosimilar approval pathway at time of submission. Like filgrastim, tbo-filgrastim is currently indicated for the treatment of neutropenia following chemotherapy; however, filgrastim is also indicated for mobilization of hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) while tbo-filgrastim is not. In Europe, tbo-filgrastim carries all the indications that filgrastim does, however, no prospective studies have been completed comparing tbo-filgrastim and filgrastim for ASCT mobilization. Therefore, we conducted a single-institution randomized phase 2 trial. Objectives: 1) To compare peripheral blood (PB) CD34+ counts, CD34+ apheresis yield, toxicity, and post-ASCT engraftment in patients mobilized with tbo-filgrastim versus filgrastim. Methods: Participants were at least 18-years-old and had multiple myeloma (MM) or non-Hodgkin's Lymphoma (NHL). Those with impaired hematologic function and those who had undergone a previous ASCT mobilization were excluded. Participants were randomized (1:1) to tbo-filgrastim or filgrastim. Tbo-filgrastim/filgrastim (10mcg/kg) was administered daily for 5 days. On the evening of Day 4, plerixafor (0.24 mg/kg) was administered; apheresis (20L) was performed on Day 5. If a participant failed to achieve the target collection goal (5.0x106 cells/kg) on Day 5, he/she continued to receive daily tbo-filgrastim/filgrastim, plerixafor, and apheresis for a maximum of 3 additional days. Participants who subsequently underwent ASCT were followed for platelet and neutrophil engraftment. Statistics: PB CD34+ counts and CD34+ apheresis yields were compared using Mann-Whitney U, engraftment using log-rank. Results: At the time of abstract submission, corresponding with interim analysis 1, 51 participants were enrolled and 49 were evaluable for analysis; 24 received tbo-filgrastim, 25 filgrastim. The median age was 60 years (range 40-77); 63% (31) were male; 86% (42) had MM, 14% (7) NHL. Both treatment arms were similar in demographics and baseline blood counts. Post-mobilization PB CD34+ counts were similar between both arms. The median PB CD34+ count on day 4 (pre-plerixafor) was 20/mcL for tbo-filgrastim and 22/mcL for filgrastim (p=0.647); on Day 5 pre-apheresis it was for 94/mcL for tbo-filgrastim and 92/mcL for filgrastim (p=0.726). CD34+ apheresis yield was also similar; the median Day 5 CD34+/kg apheresis yield was 10.9x106 for tbo-filgrastim and 12.0x106 for filgrastim (p=0.889). Seventy-five percent of the tbo-filgrastim arm reached the collection goal after one day of apheresis, 76% of the filgrastim arm did (p=0.935). Ninety-six percent of patients on the tbo-filgrastim arm reached the goal in 4 or less days of apheresis, 92% of the filgrastim arm did (p=0.576). All patients treated collected 〉 2.0x106 cells/kg, the minimum required for ASCT, following 〈 2 days of apheresis. Both treatment arms had similar toxicity. Thirty-nine patients have subsequently undergone ASCT and evaluable for engraftment, 18 on the tbo-filgrastim arm and 21 on the filgrastim arm. The median interval of neutrophil engraftment for tbo-filgrastim was 12 days compared to 11 for filgrastim (p=0.178); the median interval of platelet engraftment was 17 days for both arms (p=0.238). Mobilization, collection, toxicity, and engraftment data are summarized in Table 1. Conclusion: Tbo-filgrastim appears to be similar to filgrastim for ASCT mobilization in patients with MM or NHL. Planned study enrollment is 100 evaluable patients; updated study results will be presented. Table 1. Tbo-Filgrastim Filgrastim PB CD34+/mcl on Day 41(median & range) 20 (4-68) 22 (1-115) PB CD34+/mcl on Day 5 (median & range) 94 (18-187) 92 (11-314) CD34+/kg x106 yield on Day 5 (median & range) 10.9 (1.4-21.2) 12.0 (1.3-28.4) CD34+/kg yield 〉2.0 on Day 5 96% 92% CD34+/kg yield 〉5.0 on Day 5 75% 76% CD34+/kg yield 〉2.0 in 〈 4 days 100% 100% CD34+/kg Yield 〉5.0 in 〈 4 days 96% 92% Post-ASCT Engraftment Days to Neutrophil Engraftment (median & range) 12 (10-20) 11 (10-13) Days to Platelet Engraftment (median & range) 17 (13-23) 17 (13-22) 1-Prior to plerixafor dose Disclosures Vij: Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy; Takeda, Onyx: Research Funding. Abboud:Teva Phamaceutical: Research Funding.