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Background: Patients with multiple myeloma are frequently treated with bortezomib, a proteasome inhibitor, which is associated with treatment-related peripheral neuropathy. Older adults are at increased risk of falls compared to the general population, often leading to associated morbidity and mortality. While an association between peripheral neuropathy and falls in older adults is well-established, the relationship between bortezomib and falls in older multiple myeloma patients is unknown. Our primary aim was to determine if older patients with multiple myeloma treated with bortezomib as first-line therapy had an increased incidence of falls within the first 12 months after starting treatment. Our secondary aim was to assess the overall survival of patients who fell compared to those who did not among patients who lived more than 12 months after initiating treatment. Methods: We analyzed the SEER-Medicare database for all patients 65 years old or older diagnosed with multiple myeloma between 2007 and 2013 and were enrolled in fee-for-service Medicare part A, B and D plans. The patients' corresponding Medicare claims data were analyzed through 2014 for myeloma treatments, fall claims, and covariates of interest. The primary outcome was accidental falls (E880-E888) occurring between 14 days to 12 months after starting multiple myeloma treatment. First-line therapy was defined as any anti-myeloma treatment administered within 14 days of starting multiple myeloma treatment, with bortezomib treatment being the focal independent variable. Cox regression was performed to determine the relative risk of having a fall after controlling for other covariates. Patients who started bortezomib after first-line therapy were censored at time of bortezomib commencement. The survival analysis included only patients who survived more than 12 months of starting treatment to allow landmark analysis of falls in the first year. Results: Of 4,084 older adults with new multiple myeloma diagnoses undergoing first-line therapy, the median age was 75 (range 65-97) with 51% males. Bortezomib was used in first-line therapy for 2,052 (50%) patients, of which 157 (8%) patients experienced a fall within 12 months after starting treatment compared to 102 (5%) of patients not receiving bortezomib (p < 0.001). Bortezomib was associated with a 28% increase risk of falls (HR 1.29; 95% CI 1.00-1.65; p = 0.047). In multivariate analysis, bortezomib was not associated with an increased incidence of falls after controlling for age, gender, race, proxies for Charlson Comorbidity Index (CCI) and poor performance status, pre-existing peripheral neuropathy, falls within the 12 months prior to starting first-line myeloma treatment, depression, polypharmacy, and first-line treatment with lenalidomide (Table 1). Advancing age, history of fall(s), depression, and polypharmacy (defined as more than 10 unique prescription medications at initiation of first-line treatment), were all associated with an increased risk of falls, consistent with prior literature. In a landmark analysis of those who survived 12 months following the start of treatment, a fall was associated with a 26% increased risk of hazard for death (aHR 1.26; 95% CI 1.02-1.56; p = 0.033) after controlling for other covariates. The median OS of those with a fall was 35.7 months (95% CI 29.1-48.4) compared to 49.1 months (95% CI 47.1-52.8) for those without (p < 0.0001). Conclusion: In older adults with multiple myeloma, treatment with bortezomib was not associated with increased risk of a patient having a diagnostic code for falls. However, experiencing a fall within the year after starting treatment was associated with decreased overall survival. Limitations of the study include that the incidence of falls is likely underestimated in billing data, given prior data from our group showing a rate of self-reported falls of 26% in the year after diagnosis. Additional research, including prospective trials involving fall assessments, should be considered in older patients with multiple myeloma. Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy. Fiala:Incyte: Research Funding.

Introduction: Inositol-requiring enzyme 1α (IRE1α) is one of three principal transmembrane sensors in the endoplasmic reticulum (ER) involved in regulating the unfolded protein response (UPR). It splices X-box protein 1 (XBP1) mRNA yielding a transcription factor intimately involved in the plasma cell differentiation and proliferation. The IRE1α-XBP1 axis exhibits positive feedback functions that promote the pro-survival UPR and allows plasma cells to survive the high biosynthetic burden of immunoglobulin production, although IRE1α also has functions that promote cell death depending on the chronicity and severity of ER stress. Functional IRE1α has been identified as critical for in vitro cytotoxicity of bortezomib by Leung-Hagesteijn et al. (Cancer Cell 2013), with loss of IRE1α leading to in vitro resistance to proteasome inhibition. However, Mimura et al (Blood 2012) identified in vitro synergy with IRE1α-inhibition and bortezomib, and Papandeou et al. (Blood 2011) identified in vitro and in vivo anti-myeloma activity of a different IRE1α endonuclease inhibitor. The clinical implications of IRE1α are still poorly understood. In this study, we sought to identify associations between IRE1α mRNA expression (the level at which it is principally regulated) with treatment resistance and patient outcomes. Methods: We performed a secondary analysis of data from the MMRF CoMMpass study (IA14). In the CoMMpass study, RNAseq on CD138-enriched bone marrow cells was performed using Illumina TruSeq RNA library kits. Cox Regression analysis was used to compare the association of IRE1α expression with progression-free and overall survival. To determine if IRE1α expression is modulated following disease progression, we also identified patients who had pre- and post-treatment RNAseq data. We analyzed expression of IRE1α from the pre- and post-treatment specimens using paired T-tests comparing patients who had relapsed disease (relapse following completion of therapy) and refractory disease (progression on or within 60 days of completing therapy). Results: We included 768 patients who had IRE1α expression data at myeloma diagnosis. The median age was 63 (range 27-93) and 50% were male. Thirty percent of patients (n = 231) were considered to have high IRE1a expression at myeloma diagnosis. High IRE1α expression was associated with worse clinical outcome. Those with high expression had a 37% (aHR 1.37; 95% CI 1.10-1.72; p = 0.006) increase hazard for progression and a 55% (aHR 1.55; 95% CI 1.13-2.15; p = 0.008) increase hazard for death. We then identified 46 patients who had pre- and post-treatment RNAseq data. Twenty-two had relapsed disease while off of treatment and 24 had developed refractory disease while on treatment. Patients who had refractory disease were noted to have a significant decrease in the expression of IRE1α (p = 0.008). This was similar when we performed subset analysis of patients who were refractory to PI-based treatments (n=8; p = 0.044) and IMID-based treatments (n = 13; p = 0.054). In contrast, there was not a significant difference between pre-treatment and post-treatment IRE1α in relapsed disease (p = 0.312). Expression of other UPR elements, specifically PERK and XBP1, was not significantly downregulated in relapsed or refractory disease. Conclusion: Our study demonstrates that high expression of IRE1α at diagnosis is associated with worse outcomes, but that resistance to therapy is associated with a significant decrease in IRE1α expression. While this seems counterintuitive, it highlights the complex nature of the UPR and the roles of IRE1α. More aggressive/proliferative disease relies heavily on an adapted pro-survival UPR, highlighted by increased expression of IRE1α de novo. However, IRE1α has previously been demonstrated to be required for anti-myeloma activity of novel therapies; potentially either by clonal selection, dynamic alterations in UPR signaling, or epigenetic modifications, treatment-refractory myeloma cells downregulate the expression of IRE1α, a phenomenon not seen in those who completed treatment but subsequently relapsed. IRE1α inhibition could initially potentiate the clinical effects of novel therapies in a higher-risk population, but may also promote later resistance to them. Importantly, IRE1α could serve as a prognostic biomarker for risk-stratification at diagnosis as well as one predictive of impending resistance to therapy. Disclosures Fiala: Incyte: Research Funding. Wildes:Janssen: Research Funding; Carevive: Consultancy. Vij:Takeda: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Genentech: Honoraria; Janssen: Honoraria. Stockerl-Goldstein:AbbVie: Equity Ownership; Abbott: Equity Ownership.

The incidence of multiple myeloma is increasing as the proportion of older adults is growing rapidly. A critical evaluation of the evidence available is needed to guide the management of older patients with myeloma. A systematic review was conducted to report the prognostic value of geriatric assessment and frailty scores in older patients with multiple myeloma. We conducted a literature search in February and August 2018. Two researchers extracted the data and assessed the quality of the studies. Geriatric assessment and frailty scores were defined as those evaluating at least 2 geriatric domains. Main outcomes were mortality or toxicity. We estimated the pooled hazard ratios (HR) with 95% confidence intervals (CIs) using a random-effects model. We screened titles and abstracts of 1672 citations for eligibility. Seven studies were included in the qualitative analysis, of which 3 were included in the meta-analysis. Two studies reported similar risks of hematologic adverse events in intermediate-fit and in frail patients compared to frail, but a significantly increased risk of nonhematologic adverse events in frail patients compared to fit patients. In meta-analysis, a significantly increased HR for death was observed in patients with activity of daily living score ≤ 4 (pooled HR = 1.576; 95% CI, 1.051-2.102; χ2 = 0.87; P = .647; I2 = 0). Patients classified as frail showed higher risk of death than fit patients (pooled HR = 2.169; 95% CI, 1.002-2.336; χ2 = 3.02; P = .221; I2 = 33.7%). GA and frailty score are effective in predicting mortality in older adults with myeloma.

e19516 Background: Autologous stem cell transplantation (ASCT) followed by maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma. Maintenance typically consists of lenalidomide (LEN), however, bortezomib (BOR) and bortezomib-lenalidomide combination are other options. The respective toxicity of these regimens has not been well studied. We performed secondary data analysis to compare incidence of serious adverse events associated with each maintenance therapy group during post-ASCT maintenance treatment period. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis from the CoMMpass study. We extracted data of first-time autologous stem cell transplant patients who completed maintenance therapy post-ASCT. We categorized patients into three sub groups bortezomib, lenalidomide or combination (bortezomib and lenalidomide) maintenance therapy. Incidence rate for serious adverse events (grade 3 or higher) was calculated by number of events per 100 person-months for each maintenance therapy. Results: 231 patients were eligible for our analysis. 169 patients received lenalidomide, 27 bortezomib and 35 combination. The most common adverse event was neutropenia and second most common is pneumonia. Neutropenia incidence was 1.1,0.7 and 0.9 per 100 person-months in lenalidomide, bortezomib and combination regimens respectively. Incidence of deep vein thrombosis, GI intolerance and peripheral neuropathy 0.1 per 100 person-months respectively was observed in lenalidomide group only. Combination maintenance had the highest total adverse event incidence rate of 5.4 per 100 person-months. Incidence of 1.7 and 3.8 per 100 person-months is observed in bortezomib and lenalidomide cohorts respectively. Conclusions: Lenalidomide and bortezomib maintenance had similar incidence of serious adverse events. A higher incidence of serious adverse events was noted in the combination lenalidomide/bortezomib regimens. Interestingly, we observed lower incidence of adverse events in all groups in CoMMpass study compared to respective clinical trials involving maintenance regimens. This may be due to under reporting of adverse events in CoMMpass study. The incidence of adverse events mentioned above should be interpreted in the context of drugs and other factors involved in the disease.

Objective Autologous stem cell transplantation (ASCT) is used sparingly among myeloma (MM) patients with renal impairment due to concerns of morbidity and mortality. A number of studies have been published, but most are single-center studies and include a relatively small number of subjects limiting generalizability. Our objective is to perform a meta-analysis of the published literature. Data Sources PubMed, EMBASE, Cochrane review database, and clinicaltrials.gov were queried for the keywords “renal insufficiency, dialysis,” “autologous stem cell transplant,” and “multiple myeloma” through August 29, 2018. Study Selection Retrospective, prospective studies and sub-group analysis studies were included. Abstracts, Case reports, Case series studies and CIBTMR data analysis studies were excluded. Data Extraction and Synthesis Data was extracted based on Reviews and Meta- Analysis guidelines. Pooled risk ratios and 95% confidence intervals were calculated using DerSimonian-Laird (DL) random effects model. Heterogeneity between studies was evaluated using Q test and sensitivity analysis. Publication bias was evaluated using a funnel plot and with Egger's test and Begg's test. Outcomes were calculated by using ‘Metafor’ and ‘Meta’ packages by R-Studio and “CRAN” project. Main Outcomes and Measures Complete response (CR) was defined per standard criteria. Treatment related mortality (TRM) was defined as death within 100 days after transplant. Improvement in renal function (IRF) was defined by improvement in GFR or dialysis independence during follow up period. Progression-free survival (PFS) was defined as time from transplant to progression or death. Results A total of 177 studies were assessed for eligibility. Of those, 18 studies were eligible, which included a total of 605 patients with MM and renal insufficiency who underwent ASCT. Treatment related mortality (TRM) occurred in 12% (n=296; 95% CI, 8%- 20%) of the patients. Complete response was achieved in 39% (n=605; 95% CI, 31%-48%) and renal function improvement 10% (n=323; 95% CI 7%-15%) of patients. The odds of achieving complete response increased 42% following autologous stem cell transplantation. Median Progression free survival is about 47 (n=102; 95% CI, 36.35- 56.90) months. Keywords Renal insufficiency, Multiple Myeloma, Autologous Stem Cell Transplantation

Background: Older pts with BC receiving adjuvant tx are at increased risk of chemo tox; however, no BC-specific tool exists to quantify this risk. The Cancer and Aging Research Group (CARG) developed/validated a chemo tox score for older pts with all stages of solid tumor. The goals of this study were to: 1) build upon the CARG score by developing/validating CARG-BC (a BC specific adjuvant chemo tox score for older pts) and 2) evaluate its association with dose modifications, reduced relative dose intensity (RDI) and hospitalizations. Methods: 501 pts age ≥65 with stage I-III BC from 16 sites were accrued (300 development; 201 validation cohort). A pre-chemo assessment captured: CARG chemo tox score, BC tumor/tx variables, and additional geriatric assessment (GA) items. Grade 3-5 chemo tox by NCI CTCAE v 4.0 was captured. Univariate analysis identified chemo tox risk factors (p Results: Among 501 pts, 28 received non-standard regimens and were excluded, leaving 473 evaluable pts: 283 development and 190 validation cohort. The development cohort (median age 70; range 65-85) had Stage I (39%), II (41%), & III (20%) BC with 65% hormone positive, 24% triple negative, 27% Her2 positive; and 37% received an anthracycline. Grade 3-5 tox occurred in 46% (36% grade 3, 10% grade 4, 0.4% grade 5). The CARG score was significantly associated with grade 3-5 tox (p Conclusions: We developed and validated a risk score (CARG-BC) which identifies an older pt's risk for adjuvant BC chemo tox and is associated with dose reduction, delay, reduced RDI, and hospitalization. This tool could be considered as a part of adjuvant tx decision-making. Chemo Tox Risk Score for BC (CARG-BC) Grade 3-5 Tox (%)ScoreCARG-Score: age, # of chemo drugs, dose, hemoglobin, creatinine clearance, hearing, falls, ability to walk 1 block and take meds, decreased social activitiesLow360Middle573High613StageI330II/III552Planned Tx Duration≤ 3 mo.330> 3 mo.584AnthracyclineNo380Yes591Liver FunctionNormal450Abnormal623Ability to Walk a MileNot limited370Limited613Someone to Provide AdviceMost of Time440None to Some of Time613 CARG-BC Risk ScoreLow210-5Middle456-9High7910+ Citation Format: Hurria A, Magnuson A, Gross CP, Tew WP, Klepin HD, Wildes TM, Muss HB, Dotan E, Freedman R, O'Connor T, Dale W, Cohen HJ, Katheria V, Arsenyan A, Levi A, Kim H, Sun C-L. Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-04.

Background: Burkitt lymphoma (BL) is a rare, highly aggressive B-cell malignancy treated most successfully with brief-duration, high-intensity chemotherapeutic regimens. The benefit of the addition of rituximab to these regimens remains uncertain. We sought to examine the effectiveness of chemotherapy with and without rituximab in patients with BL. Methods: This study is a retrospective cohort study of all adult patients with BL diagnosed and treated with modern, dose-intense chemotherapeutic regimens from 1998–2008 at two tertiary care institutions. All cases were confirmed by application of WHO 2008 criteria by hematopathologists. Medical records were reviewed for patient-, disease-, and treatment- related factors as well as treatment response and survival. Factors associated with survival were analyzed using Cox proportional hazards modeling. Results: A total of 35 patients were analyzed: 18 patients received rituximab with chemotherapy (R-chemo) and 17 received chemotherapy (chemo) alone. The median age was 42 (range 20–74 years); 57% were male; 71% had Ann Arbor Stage IV disease; 33% had central nervous system involvement; 78% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. R-chemo was associated with significantly longer overall survival (OS) than chemo alone (5-year OS 70% and 29%, respectively, p = 0.040). On multivariate regression analysis, poor performance status and central nervous system involvement were associated with poorer survival. Conclusions: The addition of rituximab to chemotherapy was associated with improved OS in patients with Burkitt lymphoma. Poor performance status and central nervous system involvement were prognostically significant on multivariate analysis.

Our purpose was to determine whether geriatric assessments are associated with completion of a chemotherapy course, grade III/IV toxicity or survival in older adults with cancer.In this prospective cohort study, patients aged 65 years and older with colorectal, lung, or breast cancer or lymphoma completed a brief geriatric assessment prior to chemotherapy. Endpoints included completion of the planned number of chemotherapy cycles, grade III/IV toxicity and survival. Multivariate logistic regression determined which factors were independently associated with completion of therapy, grade III/IV toxicity or death.Sixty-five patients were enrolled in the study. The median age was 73 years (range 65–89). Geriatric syndromes were common, including depression (21.5%), dependence on others to carry out instrumental activities of daily living (38.5%) and activities of daily living (10.8%), and comorbidities (mild 47.7%, moderate 20%, severe 15.4%). Of the 65 participants, 67.6%completed the planned number of chemotherapy cycles. Curative intent therapy [OR 4.97 (95% CI 1.21–18.81)], Eastern Cooperative Oncology Group (ECOG) performance status 2–3 [OR 0.089 (0.015–0.53)] and renal function [OR 1.03 (1.00–1.06) per ml/min] were significantly associated with therapy completion. Furthermore, 31.1% experienced grade III/IV nonhematologic toxicity. Moderate to severe comorbidities significantly increased the risk of grade III/IV non-hematologic toxicity [OR 6.13 (1.65–22.74)]. Patients who received chemotherapy with curative intent had lower mortality [HR 0.15 (0.06–0.42)], while patients who reported a fall in themonth prior to chemotherapy had an increased risk of death [HR 3.20 (1.13–9.11)].Geriatric assessment is associatedwith completion of a planned number of cycles of chemotherapy, grade III/IV non-hematologic toxicity, and mortality.

The aging population and the increasing number of cancer survivors will likely be associated with more second primary malignancies due to prior cancer treatment. Since the incidence of most cancers increases with age, these treatment-associated second malignancies will likely disproportionately impact older adults. Here, we present the case of a 78-year-old man with a history of localized prostate cancer treated with external beam radiation therapy 11 years prior, who developed osteosarcoma of the ilium. Geriatric screening showed a fit older male with few comorbidities, functional independence and no other geriatric syndromes. Given the patient's preference for a limb-sparing operation, neoadjuvant chemotherapy was undertaken. With the paucity of clinical trial data on osteosarcoma in older adults, the patient was given a regimen of carboplatin (substituted for cisplatin), doxorubicin and methotrexate. Unfortunately, he developed methotrexate-induced acute kidney injury. Chemotherapy was discontinued, and he proceeded to hemipelvectomy. His postoperative course was marked by numerous complications, including delirium, depression and recurrent hospitalizations. He ultimately developed a local recurrence and elected for hospice care. This case highlights the challenges of managing older adults with treatment-associated malignancies. Clinicians face a lack of clinical trial data from which to extrapolate limitations of therapeutic options because of prior therapy and a limited ability to precisely predict which elders will experience adverse outcomes. Better approaches are needed to help older patients make decisions which fulfill their goals of care and to improve the care of older adults with treatment-associated malignancies.

Determine if highly proliferative head and neck squamous cell carcinomas, assessed by pretreatment Ki-67 expression, respond more robustly to induction chemotherapy (IC) that is selectively toxic to cycling cells. Retrospective analysis of 59 patients treated with IC and chemoradiation. IC included either nab-paclitaxel, cisplatin, 5-FU and cetuximab (APF-C, n = 27) or docetaxel, cisplatin, 5-FU +/− cetuximab (TPF+/−C, n = 32). Ki-67 expression was assessed by immunohistochemistry. Tumor response (complete/partial/stable/progressive) at the primary site after two IC cycles was evaluated by visual examination in all patients. In the APF-C sub-group, tumor response (primary site and neck nodes) after two IC cycles was evaluated by computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT. Ki-67 expression (median 66%, range: 16–97) did not differ across the tumor response categories assessed by visual examination (p = 0.95), CT (p = 0.30), or FDG-PET/CT (p = 0.65). Median decrease in summed SUVmax of measured lesions was 71.6% (range: 8.3–100%). The Pearson correlation coefficient between Ki-67 expression and the percent decrease in summed SUVmax was 0.48 (p = 0.02). Ki-67 expression was not different between those with or without a relapse (median: 60 and 71%, p = 0.10). In multivariate regression analysis (MVA) controlling for p16 positive oropharyngeal SCC status and smoking status, Ki-67 expression was not significantly associated with tumor response by visual examination (coefficient estimate −0.002, standard error 0.010, p = 0.84), CT (coefficient estimate −0.007, standard error 0.011, p = 0.54), FDG-PET/CT (coefficient estimate 0.006, standard error 0.008, p = 0.51), the percent decrease in summed SUVmax (coefficient estimate 0.389, standard error 0.222, p = 0.09), or relapse events (OR = 1.02(95%CI:0.99–1.05), p = 0.28). No significant relationships were found in MVA between pretreatment Ki-67 expression and tumor response to IC or to relapse.

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.

Recent treatment advances have greatly improved the prognosis of patients with multiple myeloma. However, some of these newer, more effective treatments are intensive and expensive and their use remains low, particularly among black patients.In the current study, the authors reviewed the use patterns of stem cell transplantation and bortezomib using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database.After controlling for overall health and potential access barriers, black patients were found to be 37% (P.0001) less likely to undergo stem cell transplantation, and 21% (P.0001) less likely to be treated with bortezomib. Moreover, the authors found that the underuse of these treatments was associated with a 12% increase in the hazard ratio for death among black patients (P = 0.0007).Eliminating health disparities, a current focus of US public policy, is highly complex, as illustrated by the results of the current study. In patients with multiple myeloma, treatment disparities are not completely explained by potential access barriers. Additional factors, such as structural barriers in the health care system and individual decision making among black and white patients, must be explored to fully explain the disparity. Cancer 2017;123:1590-1596. © 2017 American Cancer Society.

Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib. Experimental Design: Patients with stage II–IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUVmax) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated. Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related (n = 2: nausea, duodenal perforation) or unrelated (n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%–74%). Partial metabolic response (≥25% reduction in SUVmax) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%–52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients. Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186–94. ©2016 AACR.

Cancer and its treatment can lead to a myriad of adverse events and negatively impact quality of life of older cancer patients and survivors. Unmet physical activity needs vary across the cancer continuum and remain an important yet understudied area of research in this population. Exercise interventions have been shown to be effective in treating both the physical and psychological declines associated with cancer and its treatment, with a potential to improve cancer-related outcomes. Despite the current evidence, exercise is clearly underutilized due to several barriers and knowledge gaps in existing trials that include appropriate population identification, design, and outcome measures selection. The benefits of regular exercise in both the primary and secondary prevention of chronic conditions are well established in the non-cancer population. In older cancer patients and survivors, further research is needed before exercise gains widespread acceptance. The Cancer and Aging Research Group convened experts in exercise, aging and cancer to evaluate current scientific evidence and knowledge gaps in geriatric exercise oncology. This report summarizes these findings and provides future research directions.

Survival in older adults with cancer varies given differences in functional status, comorbidities, and nutrition. Prediction of factors associated with mortality, especially in hospitalized patients, allows physicians to better inform their patients about prognosis during treatment decisions. Our objective was to analyze factors associated with survival in older adults with cancer following hospitalization. Through a retrospective cohort study, we reviewed 803 patients who were admitted to Barnes-Jewish Hospital’s Oncology Acute Care of Elders (OACE) unit from 2000 to 2008. Data collected included geriatric assessments from OACE screening questionnaires as well as demographic and medical history data from chart review. The primary end point was time from index admission to death. The Cox proportional hazard modeling was performed. The median age was 72.5 years old. Geriatric syndromes and functional impairment were common. Half of the patients (50.4 %) were dependent in one or more activities of daily living (ADLs), and 74 % were dependent in at least one instrumental activity of daily living (IADLs). On multivariate analysis, the following factors were significantly associated with worse overall survival: male gender; a total score

Falls in older adults with cancer are more common than in noncancer controls, yet no fall-risk screening tool has been validated in this population. We undertook a cross-sectional pilot study of the Falls Risk Questionnaire (FRQ) in 21 adults aged ≥65 receiving systemic cancer therapy. Participants completed the FRQ, geriatric assessment measures, and a measure of fear-of-falling. The recruitment rate was 87.5 %, with 95.2 % completion of the FRQ and additional geriatric assessment and quality of life measures. The FRQ correlated significantly with the Timed Up and Go test (Pearson r 0.479, p = 0.028). In addition, the FRQ score correlated directly with fear-of-falling and inversely with QOL, particularly physical health and neurotoxicity subscales. In conclusion, the FRQ was feasible in older adults receiving cancer therapy and correlates with measures of physical performance, functional status, and fear-of-falling. The FRQ may prove to be a valuable fall-risk screening tool to implement fall-prevention interventions in this vulnerable population of older adults with cancer.

Objectives To measure short-term changes in physical and cognitive function and emotional well-being of older adults receiving intensive chemotherapy for acute myeloid leukemia (AML). Design Prospective observational study. Setting Single academic institution. Participants Individuals aged 60 and older with newly diagnosed AML who received induction chemotherapy (N = 49, mean age 70 ± 6.2, 56% male). Measurements Geriatric assessment (GA) was performed during inpatient examination for AML and within 8 weeks after hospital discharge after induction chemotherapy. Measures were the Pepper Assessment Tool for Disability (activity of daily living, instrumental activity of daily living (IADL), mobility questions), Short Physical Performance Battery (SPPB), grip strength, Modified Mini-Mental State examination, Center for Epidemiologic Studies Depression Scale, and the Distress Thermometer. Changes in GA measures were assessed using paired t-tests. Analysis of variance models were used to evaluate relationships between GA variables and change in function over time. Results After chemotherapy, IADL dependence worsened (mean 1.4 baseline vs 2.1 follow-up, P < .001), as did mean SPPB scores (7.5 vs 5.9, P = .02 for total). Grip strength also declined (38.9 ± 7.7 vs 34.2 ± 10.3 kg, P < .001 for men; 24.5 ± 4.8 vs 21.8 ± 4.7 kg, P = .007 for women). No significant changes in cognitive function (mean 84.7 vs 85.1, P = .72) or depressive symptoms (14.0 vs. 11.3, P = .11) were detected, but symptoms of distress declined (5.0 vs 3.2, P < .001). Participants with depressive symptoms at baseline and follow-up had greater declines in SPPB scores those without at both time points. Conclusions Short-term survivors of intensive chemotherapy for AML had clinically meaningful declines in physical function. These data support the importance of interventions to maintain physical function during and after chemotherapy. Depressive symptoms before and during chemotherapy may be linked to potentially modifiable physical function declines.

Background: For patients relapsing after initial autologous stem cell transplantation (ASCT), a second ASCT is a potential, although infrequently used, salvage option. Until recently, the benefits of second ASCT were unclear but recent prospective studies have shown second ASCT to improve PFS and OS compared to conventional salvage therapy. However, these studies have included few patients who received maintenance therapy following initial ASCT as maintenance therapy is a relatively recent innovation and is not standard of care in many EU countries where these studies where these studies were completed. Therefore, it is not currently clear if these patients benefit similarly from second ASCT. Methods: We performed retrospective chart review of patients with multiple myeloma that received two ASCTs, one for initial treatment and one for salvage at time of relapse, between 2008 and 2016 at our institution. We identified 30 who received maintenance therapy following initial therapy; 2 patients were excluded as they experienced treatment related mortality prior to disease assessment post-ASCT, leaving 28 for the analysis. Results: The median age of the study population was 59 years (range 48-69) at second ASCT. 64% (n = 18) were males, 36% (n = 10) females. Prior to initial ASCT, the median number of induction cycles was 4 (range 2-11). 86% (n = 24) of patients received bortezomib during induction, 39% (n = 11) lenalidomide, 7% (n = 2) cyclophosphamide, and 11% (n = 3) received another agent. All patients received melphalan conditioning for initial ASCT. Maintenance therapy consisted mostly of lenalidomide (93%, n = 26); 7% (n = 2) had bortezomib maintenance due to lenalidomide intolerance. The overall response rate (ORR) was 100% (n = 28); the complete response rate was 39% (n =11). The median progression-free survival (PFS) post-ASCT was 31 months (range 9-57), the median interval between initial and salvage ASCT was 38 months (range 22-63). At relapse, 93% (n =26) received reinduction chemotherapy while 7% (n = 2) went directly to salvage ASCT. The median number of reinduction cycles was 4 (range 2-28). 54% (n = 15) of patients received carfilzomib during reinduction, 46% (n = 13) bortezomib, 32% (n = 9) cyclophosphamide, 29% (n = 8) lenalidomide, 14% (n = 4) pomalidomide, and 7% (n = 2) received another agent. Prior to second ASCT, 79% (n =22) received melphalan conditioning, while 21% (n = 6) received BEAM. 79% (n = 22) received maintenance therapy post transplantation; 39% (n = 11) received bortezomib, 21% (n = 6) pomalidomide, 11% (n = 3) lenalidomide, 7% (n =2) carfilzomib, 18% (n = 5) were observed off maintenance, and 4% (n = 1) had frank progression post-ASCT prior to starting maintenance. The overall response rate (partial response or better) was 86% (n = 24); the complete response rate was 21% (n = 6). The median estimated PFS was 12 months (95% CI 10-15). The median duration of follow-up was 16 months; the estimated 2 year overall survival was 49%. Conclusion: In patients who relapse post-ASCT with maintenance therapy, the PFS following salvage ASCT is ~40% that of the initial ASCT. Strategies to improve outcomes using novel reinduction, conditioning, and post-transplant maintenance regimens are needed for these patients. Disclosures Wildes:Carevive Systems: Consultancy. Vij:Shire: Consultancy; Jazz: Consultancy; Karyopharma: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

Background: In the current era, autologous stem cell transplant (ASCT) remains an effective form of treatment for patients diagnosed with multiple myeloma (MM), but it is not curative and a relapse is inevitable. A second, or salvage, ASCT provides better outcomes than conventional chemotherapy but it is infrequently used. Maintenance therapy after initial ASCT has been adopted as the standard in the US; however, there is limited data on the effects of maintenance therapy following salvage ASCT and the benefits are still unclear. Methods: We performed retrospective chart review of all patients with MM who received a second, salvage ASCT at time of first relapse at Washington University in St. Louis from 2008 to 2016. We identified two cohorts of patients, those who received maintenance therapy following salvage ASCT and those who did not. Patients who received maintenance therapy post-initial ASCT were excluded as the objective of this study was to determine the impact of maintenance post-salvage ASCT and maintenance post-initial ASCT may confound the results. Results: Sixty-five patients (who underwent second/salvage ASCT) were identified. Three were excluded from the analysis-two had treatment-related mortality following salvage ASCT and one received maintenance other than a proteasome inhibitor (PI) or an immunomodulatory drug (IMID). The maintenance cohort consisted of 31 patients, with 68% (n = 21) males and 32% (n = 10) females; the median age at salvage ASCT was 61 years (range 38-73). The no-maintenance cohort consisted of 31 patients as well with 45% (n = 14) males and 55% (n = 17) females. Their median age at salvage ASCT was 62 years (range 44-74). The characteristics of the two cohorts are summarized in Table 1. Most patients received PIs and/or IMIDs as part of their induction regimens prior to initial ASCT. All received melphalan conditioning. The response to treatment was similar between the two cohorts, with respective CR rates of 68% (n = 21) and 77% (n = 24) and median progression-free survival (PFS) of 46 months compared to 33 months. Following relapse, 16% (n = 5) of patients in the no-maintenance cohort proceeded directly to salvage ASCT without re-induction. All other patients received re-induction, mostly with PIs and/or IMIDs, with a median of 4 cycles for the maintenance cohort and 2 cycles for the no-maintenance cohort. For conditioning prior to salvage ASCT, 4 patients received Velcade-BEAM conditioning as part of a prospective trial at our site (NCT01653418); 3 from the maintenance cohort and 1 from the no-maintenance cohort. The rest received melphalan conditioning. Both cohorts had a CR rate of 52% (n = 16) post-salvage ASCT. Maintenance therapy after salvage ASCT consisted of lenalidomide (74%, n = 23), bortezomib (23%, n = 7), or pomalidomide (3%, n = 1). Three of the patients on bortezomib were originally started on lenalidomide but were switched due to intolerance. At time of data collection, the median follow-up was 49 months (range 9-105) for the maintenance cohort and 61 months (range 19-113) for the no-maintenance cohort. 45% (n = 14) of patients in the maintenance cohort and 90% (n = 28) of the no-maintenance cohort had relapsed. In the maintenance cohort, PFS following salvage ASCT was similar to what was observed following initial ASCT. The median estimated PFS post-salvage ASCT was 53 months (95% CI 42-64) compared to 46 months post initial ASCT (p = 0.144). Conversely, in the no-maintenance cohort PFS following salvage was only about 60% that of initial ASCT (21 months [95% CI 18-24]; compared to 33 months; p = 0.002). Conclusion: These results suggest that maintenance following salvage ASCT is associated with improved outcomes. Although patients who received maintenance post-initial ASCT were excluded, the benefits of maintenance post-salvage ASCT may extend to them as well. Ongoing prospective clinical trials will further clarify these benefits. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wildes:Janssen: Research Funding. Vij:Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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 Results: Median follow-up was 16.8 months (range 0.1-52.4). In the initial multivariate analyses, the following were identified as significantly associated with an increased risk of mortality (Table 2): HCT-CI scores ≥5 (p Survival after HCT was 58% at 2-years. Initial unadjusted analyses showed significantly lower risks of mortality in association with receiving allogeneic HCT (p=0.0003). These findings were similar in pts with intermediate (p=0.0005) or unfavorable (p However, in the adjusted models, the advantage of HCT in reducing mortality rates was lost both in the overall population (p=0.21, see figure) as well as in the other groups (p>0.54, 0.40, and 0.51, respectively, Table 3). Formal tests of interactions (Table 3) showed no statistically compelling evidence that the association of HCT and mortality varies with respect to the timing of mortality or to the underlying ELN risk. Conclusions: In a prospective observational study, adjusting for key AML-specific and pt-specific variables negated the observed benefit of HCT over non-HCT therapies in reducing mortality rates among AML pts. Our results might reflect 1) improvement in supportive care and non-HCT therapies, 2) a relatively high non-relapse mortality early after HCT and the need for longer follow-up to demonstrate an adjusted benefit of HCT, and 3) the high selectivity of the transplant eligibility process, as we accounted here for variables that are often ignored in "genetic assignment" randomized studies (i.e. comorbidities and function). New randomized trials are needed; however, these trials have to be more inclusive of vulnerable pts and measure pt-specific variables. Trials focusing on reducing burden of comorbidities, frailty and poor function are needed alongside trials to treat AML with or without HCT. Disclosures Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; CTI Biopharma: Consultancy; Incyte: Consultancy. Shami:JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees; Lone Star Biotherapies: Equity Ownership; Pfizer: Consultancy. Rizzieri:Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Wang:Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Alexion: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Otsuka: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.

Introduction: Acute myeloid leukemia (AML) is most frequently diagnosed in older patients (pts), whose median survival is less than 1 year. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment. However, older pts often have significant comorbidities and other geriatric health problems, and the effect of these on the probability of receiving HCT is unknown. To this end, we designed a prospective, multi-center, longitudinal, observational study dating from first presentation of adult pts with AML to be treated at one of 13 different referral centers that provide both AML treatment and HCT. We examined the effects of different variables (see methods) on the probability to 1) survive long enough to receive HCT and 2) to receive HCT if such survival occurred. 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 instrumental activities of daily living (IADL) and activities of daily living (ADL); frailty including walk test; geriatric assessment (GA) including cognition; Karnofsky performance status (KPS); QOL including the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT), Euro-QOL 5-Dimension scale (EQ-5D), 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. High-risk myelodysplastic syndromes (MDS) receiving AML-like therapy were included. We used competing risk Cox regression analyses, treating HCT as the event of interest and death without HCT as a competing risk, with staggered entry (left truncation) at time of consent. Associations between variables were assessed both at enrollment and over time. Results: The overall rate of HCT at 9 months after enrollment was 43% (Figure 1) and 92% of pts who received HCT did so by the 9 month mark. In multivariate analyses, death without HCT (Table 2) was associated with augmented HCT-CI scores ≥5 (HR:2.11, p Among survivors (Table 3), low likelihood to receive HCT was associated with age ≥70 years (HR:0.40, p=0.0001), low ELN risk (HR:0.28, p Conclusions: In a prospective, observational, multi-center study, increasing age, comorbidity burden, ELN risk, low-intensity initial AML induction regimen, depression, and functional dependence increase risks of early mortality without HCT. In those who survived long enough to potentially receive HCT, age up to 69 years and/or multiple comorbidities were not found to be barriers to HCT, likely reflecting the widespread use of reduced-intensity conditioning regimens. However, the independent sharp decline in receipt of HCT in pts aged 70-80 years suggests continued bias, although pts in this age group have been shown to derive similar benefit from HCT as younger pts. Use of objective comorbidity and GA tools rather than age per se to decide on HCT is encouraged. The adverse impact of impairments in psychological health and function on survival and of impairments of cognition, geriatric health, and performance status on receipt of HCT emphasize the need for interventions that target these health limitations in conjunction with AML treatment to improve outcomes. Finally, the benefit of intensive vs. less-intensive induction therapies should be addressed with a randomized trial. Disclosures Gerds: Celgene: Consultancy; Apexx Oncology: Consultancy; Incyte: Consultancy; CTI Biopharma: Consultancy. Shami:Lone Star Biotherapies: Equity Ownership; Baston Biologics Company: Membership on an entity's Board of Directors or advisory committees; JSK Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy. Rizzieri:Arog: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teva: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang:Novartis: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; Jazz: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Consultancy; Jazz: Speakers Bureau; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Faderl:Jazz Pharmaceuticals: Employment, Equity Ownership. Koprivnikar:Amgen: Speakers Bureau; Otsuka: Consultancy; Alexion: Consultancy, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Becker:GlycoMimetics: Research Funding.

Background: Advances in the treatment for multiple myeloma (MM) have dramatically improved outcomes for younger patients. Older adults, particularly those 80 years of age or older at diagnosis, have seen more modest gains. MM incidence increases with age, and as more of the population is living later into life, the segment of the MM population over 80 will continue to grow. In this study, we sought to better understand the characteristics, treatment, and outcomes of older patients with MM. Methods: We identified all patients diagnosed with MM at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2007-2013 to determine incidence and outcomes. Subset analysis was then performed on patients included in the SEER-Medicare linked database who were enrolled in Medicare Parts A, B, and D to further explore patient characteristics and treatment patterns. Results: The incidence of MM increases over age, peaking after age 80. The annual incidence for those aged 65-69, 70-74, 75-79, 80-84 and 85+ was 24.4, 32.7, 39.5, 42.8 and 36.4 per 100,000, respectively. Based on 2010 US population estimates, approximately 4,500 new cases of MM were diagnosed annually 2007-2013 in patients age 80 or older. In that period, 8,093 cases, approximately 1,150 per year, were reported to SEER. The estimated median overall survival (OS) of these patients was 14 months (95% CI 13.2-14.8). The estimated relative 12 month survival was 58.9% (95% CI 57.4-60.4) compared to their peers without cancer. Of the 8,093 cases of MM reported to SEER during the study period, 2,385 were present in the SEER-Medicare linked dataset. Of these, 225 were identified as smoldering MM using a previously established algorithm (Fiala, et al, JCOCCI, 2018) and excluded leaving 2,160 for the analyses. The median age was 84 (range 80-100) and 55% were female. 81% were white, 13% black or African-American, and 6% another race. At disease presentation, 22% had claims indicating hypercalcemia, 61% renal failure or chronic kidney disease, 59% anemia, and 34% MM bone involvement. The estimated median OS was 13.4 months (95% CI 12.2-15.1). Only 52% of patients had claims indicating they received systemic MM treatment within 6 months post-diagnosis. Nearly all that did received novel agents; 38% received bortezomib-based treatment, 41% immunomodulatory drug (IMID)-based, and 14% both. The others received antineoplastic chemotherapies such as melphalan or cyclophosphamide. Interestingly, bortezomib utilization increased incrementally from 25% of patients treated in 2007 to 62% in 2013 while IMID utilization declined from 67% to 49%. The median OS of those receiving treatment was 21 months (95% CI 18.5-23.1) compared to 6.3 months (95% CI 5.3-7.3) for those who did not (p Conclusions: The outcomes of patients with MM over 80 years old are still relatively poor; nearly half of the patients do not receive systemic treatment and for those who do the median OS is just 21 months. The population over 80, when MM incidence peaks, is projected to triple over the next few decades. It is imperative that we improve our understanding of the needs of this vulnerable subgroup of patients of MM. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Despite data supporting the safety and efficacy of treatment for many older adults with AML, Methods: We conducted semi-structured interviews with 13 community oncologists (9 states) and 9 patients aged ≥60 with AML at any stage of treatment to elicit potential factors that influence treatment decisions. Patients were recruited from the outpatient clinics in a single institution and oncologists were recruited via email using purposive samples (patients: based on treatment received and stage of treatment; oncologists: based on practice location). Interviews were audio-recorded and transcribed. We utilized directed content analysis and adapted the decision-making model introduced by Zafar et al. to serve as a framework for categorizing the factors at various levels. A codebook was provisionally developed. Using Atlas.ti, two investigators independently coded the initial transcripts and resolved any discrepancies through an iterative process. The coding scheme was subsequently applied to the rest of the transcripts by one coder. Results: Median age of the oncologists was 37 years (range 34-64); 62% were females, 92% were white, 38% had practiced more than 15 years, and 92% reported seeing Conclusions: Treatment decision-making for older patients with AML is complex and influenced by many factors at the patient, disease/treatment, physician, and organizational levels. Despite studies supporting the utility of objective fitness assessments, these were not commonly performed in the community due to several barriers. Our framework will be useful to guide a larger study to assess real-life treatment decision-making in the community settings. We also identified several barriers raised by community oncologists that could be targeted to allow incorporation of objective fitness assessments. Figure 1. Figure 1. Disclosures Liesveld: Onconova: Other: DSMB; Abbvie: Honoraria. Stock:Jazz Pharmaceuticals: Consultancy. Majhail:Anthem, Inc.: Consultancy; Atara: Honoraria; Incyte: Honoraria. Wildes:Janssen: Research Funding. Klepin:Genentech Inc: Consultancy.

Introduction: Venous thromboembolism (VTE) is a common cause of morbidity and mortality among patients with multiple myeloma (MM). Thromboprophylaxis is a safe and effective way to decrease VTE in other high-risk populations. Current guidelines recommend use of thromboprophylaxis in MM patients at high-risk of VTE, but no validated model predicts VTE in MM. A risk prediction model for VTE in MM would allow for use of thromboprophylaxis in MM patients at high-risk of VTE while sparing those at low risk. Therefore, we sought to develop a risk prediction model for VTE in MM. Patients and Methods: Using a nationwide cohort of Veterans, we identified 4,448 patients diagnosed with MM between 1999 and 2014. We retrospectively followed patients for 180 days after start of MM chemotherapy. We identified candidate risk factors through literature review for inclusion into the time-to-event models. We used the methods of Fine and Gray to model time to VTE while accounting for the competing risk of (non-VTE) death. To minimize immortal time bias, all treatment variables were entered as time-varying variables. Using a backward, step-wise approach, we retained variables in the model with a p ≤ 0.05, or with a p < 0.50 with findings consistent with prior literature. Using beta coefficients, we developed a risk score by multiplying by a common factor and rounding to the nearest integer. The risk score for each patient was the sum of all scores for each predictor variable. We assessed model performance with Harrell's c-statistic and with the inverse probability of censoring weighting approach. Through bootstrap analysis, we validated the model internally. We carried out all statistical analyses using SAS version 9.4 (SAS Institute, Cary, NC). Results: The median time from MM diagnosis to start of treatment was 37 days. A total of 53 patients (5.7%) developed VTE within 6 months after start of MM-specific therapy. The mean time from chemotherapy start to VTE was 69 days, with 69% of VTE events occurring in the first 3 months of chemotherapy. The factors associated with VTE were combined to develop the IMPEDE VTE score (IMID 3 points, BMI 1 point, Pathologic fracture pelvis/femur 2 points, ESA 1 point, Dexamethasone (High-dose 4 points, Low-Dose 2 points)/Doxorubicin 2 points, Ethnicity/Race= Asian -3 points, history of VTE 3 points, Tunneled line/CVC 2 points) (Table 1). In addition, use of therapeutic anticoagulation (-5 points) with warfarin or low molecular weight heparin (LWMH) and use of prophylactic LMWH or aspirin (-2 points) were associated with a decreased risk of VTE. The model showed satisfactory discrimination in both the derivation cohort (Harrell's c-statistic = 0.66) and in the bootstrap validation, c-statistic = 0.65 (95% CI: 0.62 - 0.69). Using three risk groups, the incident rate of VTE with the first 6-months of starting chemotherapy was 3.1% for scores ≤ 3 (low-risk), 7.5% for a score of 4-6 (intermediate-risk), and 13.3% for patients with a score of ≥ 7 (high-risk). The risk of developing VTE within 6 months after starting chemotherapy was significantly higher for patients with intermediate- and high-risk scores compared to low-risk (Table 2). Conclusions and Relevance: We developed a risk prediction rule, IMPEDE VTE, which can identify patients with MM at high-risk of developing VTE after starting chemotherapy. IMPEDE VTE could guide clinicians in selecting patients for thromboprophylaxis in MM. Disclosures Sanfilippo: BMS/Pfizer: Speakers Bureau. Wang:Daiichi Sankyo: Consultancy, Other: Travel. Wildes:Janssen: Research Funding. Mikhael:Onyx, Celgene, Sanofi, AbbVie: Research Funding. Carson:Flatiron Health: Employment; Washington University in St. Louis: Employment; Roche: Consultancy.

Introduction: Despite significant advances in multiple myeloma (MM) therapy, disease progression through multiple novel treatments is often inevitable. Quad-refractory MM (refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide), or penta-refractory MM (refractory to an anti-CD38 monoclonal antibody as well) portends a poor prognosis, with few subsequent lines of treatment currently available. We and others have used bendamustine combined with corticosteroids as a salvage regimen, but there is a paucity of outcomes data in this heavily pretreated population. Methods: We conducted a retrospective study to identify all patients who received bendamustine with corticosteroids for quad- or penta-refractory MM at our institution between 2013 and 2018. Disease response and refractoriness were defined by IMWG criteria. The primary endpoint was overall response rate (ORR) defined as PR or better. Secondary endpoints included overall survival (OS) and duration of response (DOR). Results: Twenty-seven patients were identified; 5 patients were quad-refractory, and 22 penta-refractory (Table 1). Twenty-two (81%) patients had at least one prior autologous stem cell transplant and 1 had a prior allogeneic. The median age at time of bendamustine was 61, 52% were female, and 85% were white. All patients received bendamustine at a dose of 90mg/m2 on days 1 and 2 of a 28 day cycle. Twelve patients (44%) received more than one cycle (range: 1-8). The overall response rate was 26%. While no patient achieved CR, 4 achieved VGPR and 3 a PR. Two of the 5 (40%) quad-refractory patients responded compared to 5 of the 22 (23%) penta-refractory. Sixteen (59%) were primary refractory to bendamustine and one patient went onto hospice prior to response evaluation. Overall the median PFS was 1.4 months (95% CI 1.1-1.6) and median OS was 8.7 months (95% CI 2.3-15.0). For responders (≥PR), median DOR was 6.6 months (95% CI 0.0-13.7) and median OS was 14.0 months (95% CI 0.6-27.4). Conclusion: The prognosis of quad- and penta-refractory MM remains poor. In this heavily pre-treated population, bendamustine demonstrates a 26% ORR (95% CI 11%-46%). The DOR and OS of the patients was poor but highly heterogeneous. Those who did respond to bendamustine had notably improved OS. Given the limited available options for quad- and penta-refractory MM, bendamustine remains a reasonable salvage therapy. Prospective trials are warranted perhaps including additional agents that are effective in penta-refractory patients. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Introduction: Multiple Myeloma (MM) remains difficult to treat despite significant advances in treatment options. Daratumumab (dara) as a single-agent or in combination with other treatments has considerable efficacy even among patients with highly-refractory disease. However, nearly all patients will fail dara. Dara frequency decreases throughout the treatment, from weekly eventually to monthly dosing, which may in part contribute to relapse. It has been hypothesized that increasing the frequency of dara may help restore responses in patients progressing on dara, but little data exists. Methods: In this retrospective case study, we identified 5 patients from our clinical database who received standard dara (weekly for 2 cycles, every other week for 4 cycles, then monthly thereafter) as a single agent or in combination, who had frequency re-escalated at relapse in attempt to recapture response. Results: Patient 1 is a 67 yo male with quad-refractory MM who received single-agent dara. He had a PR following 1 cycle but disease plateaued, ultimately progressing with rising M-protein following cycle 7 of treatment. Dara frequency was re-escalated to once weekly and the patient once again obtained a PR following the first cycle. The patient received 2 additional cycles at which time he had further evidence of PD and was switched to alternative treatment. Patient 2 is a 68 yo female with quad-refractory MM who received single-agent dara. She had a PR following 1 cycle but disease plateaued, ultimately progressing with rising free-light chains following cycle 12 of treatment. Dara frequency was re-escalated to once every other week. The patient had a mild reduction free-light chains (not meeting PR) and went on to receive 8 additional cycles before having further evidence of PD and switching to supportive care only. Patient 3 is a 73 yo male with refractory MM who received dara in combination pomalidomide (pom) and dexamethasone (dex). The patient had previously progressed on pom/dex. He had a PR following 2 cycles but disease plateaued, ultimately progressing with rising free-light chains following cycle 8 of treatment. Dara frequency was re-escalated to once weekly. The patient had a mild reduction in free-light chains (not meeting PR) and went on to receive 5 additional cycles before having further evidence of PD and switching to alternative treatment. Patient 4 is a 68 yo male with refractory MM who received single-agent dara. He had a PR following 1 cycle, and a VGPR following cycle 3. The patient later progressed following 14 cycles with rising M-protein and new lesion requiring XRT. Dara frequency was re-escalated to once weekly. The patient had a mild reduction M-protein (not meeting PR) and went on to receive 8 additional cycles before having further evidence of PD and switching to alternative treatment. Patient 5 is a 69 yo female with refractory MM who received dara/pom/dex. She was previously naïve to pom. The patient initially had stable disease but progressed with increasing free-light chains following cycle 6. Dara frequency was re-escalated to once weekly. The patients free-light chains returned to baseline levels and she went on to receive an additional 5 cycles before having further evidence of PD and switching to alternative treatment. Conclusion: Increasing dara frequency, can result in stabilization or improvement of myeloma disease markers in patients who were previously relapsing. This strategy may be clinically beneficial to patients who are showing signs of early biochemical progression but are otherwise doing well. Prospective trials are warranted to further evaluate this approach. Disclosures Vickroy: Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Bristol-Meyers Squibb: Honoraria, Speakers Bureau. Peery:Novartis: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Schroeder:Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction: Despite the recent introduction of novel agents for multiple myeloma (MM), the disease remains incurable and invariably progresses through these new therapies. Patients with quad-refractory MM (refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide) and penta-refractory MM (refractory to an anti-CD38 monoclonal antibody as well) are left with few treatment options and poor prognoses. The chemotherapy regimen of dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) has demonstrated efficacy in the treatment of relapsed/refractory MM. We and others employ DCEP as a salvage regimen, however, few outcomes data exist in this heavily pretreated population. Methods: We conducted a retrospective study to identify all patients who received DCEP for quad- or penta-refractory MM at our institution between 2013 and 2018. Disease response and refractoriness were defined by IMWG criteria. The primary endpoint was overall response rate (ORR) defined as PR or better. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and duration of response (DOR). Results: We identified 31 patients who received DCEP, 8 (26%) for quad-refractory and 23 (74%) for penta-refractory MM (Table 1). Twenty-eight (90%) had at least one autologous stem cell transplant, and one had a prior allogeneic transplant. Sixteen (52%) were female, 27 (87%) were white, and median age at DCEP was 60. Median number of prior treatment regimens was 8. All patients received dexamethasone (40mg/day), cyclophosphamide (400mg/m2/day), etoposide (40mg/m2/day), and cisplatin (10mg/m2/day) on days 1-4 (Lazzarino et al. 2001). Cycles were generally 28 days in length, but doses were delayed in cases of cytopenias or other toxicities. Dose reductions occurred in cases of renal impairment or prolonged cytopenias. Twenty patients (65%) received more than one cycle (range: 1-5). The overall response rate was 35%. One patient achieved CR allowing him to proceed to a second autologous transplant. One patient achieved a VGPR, 9 (29%) a PR. Four of the 8 (50%) quad-refractory patients responded compared to 7 of the 23 (30%) of the penta-refractory patients. Eleven (35%) were primary refractory to DCEP, and two patients died after one cycle prior to response assessment. The overall median PFS was 2.7 months (95% CI 1.5-3.8) and median OS was 6.2 months (95% CI 4.4-7.8). For responders, median DOR was 4.2 months (95% CI 3.0-5.4) and median OS was 9.0 months (95% CI 7.2-10.9). Conclusion: Quad- and penta-refractory MM carry a grim prognosis. In our retrospective study, DCEP led to a notable ORR of 35% (95% CI 19%-55%) in this very heavily-treated population, and suggests that it remains a reasonable salvage therapy. Furthermore, it supports prospective study of this regimen, possibly in combination or in comparison with other agents effective in quad- or penta-refractory MM. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background: Nearly half of older African-Americans who develop multiple myeloma (MM) do not receive systemic treatment. Those who do are less likely to receive newer treatments, such as novel agents and stem cell transplant, than their peers. In this study, we sought to determine if disparities in resource utilization exist even among patients receiving similar treatment. Methods: All newly diagnosed MM cases from 2007-2013 in the SEER-Medicare dataset were reviewed along with their corresponding claims data through 2014. We excluded cases 1) not enrolled in Medicare Part A, B, and D; 2) HMO enrollees; 3) those diagnosed prior to age 65; 4) all patients who did not receive a proteasome inhibitor and/or an immunomodulatory drug within 6 months; 5) those who underwent stem cell mobilization or transplantation; or 6) died within 12 months of MM diagnosis. All reported medical costs including both those paid by Medicare and patient copays for the first 12 months post-diagnosis were captured and adjusted for inflation. Results: 2,841 patients were included. The median age was 74 at diagnosis (range 65-96) and 51% were male. 79% (n = 2,247) were white, 14% (n = 403) African-American/Black, and 7% (n = 191) were another race. Overall, the median expenditure was $127,054 in the 12 months post-diagnosis; $121,400 for African-Americans, $127,810 for whites, and $119,209 for other races. After controlling for age, gender, comorbidities, a proxy measure of performance status, and MM related renal impairment and bone disease, African-American patients had $10,524 less in overall expenditures on average than white patients. This can partly be attributed to lower expenditures on MM drugs. On average African-American patients had $5,520 less in MM drug expenditures (p = 0.0062). African-Americans also had 9.3 less days of interaction with outpatient services compared to their white peers (p < 0.0001), but 4.6 more days in inpatient settings (p = 0.0208). There was no statistically significant difference between white patients and patients of races other than white or African-American in overall expenditure or MM drug expenditure but members of other races had 8.2 less days of interaction with outpatient services (p = 0.0004) and 5.7 less days in inpatient settings (p = 0.0350). The estimated median overall survival for African-American patients was 44 months (95% CI 40-51) compared to 47 (45-50) for white patients and 57 (44-66) for patients of other races (p = 0.097). Race was not associated with overall survival in multivariate analysis. Conclusion: Minority patients with MM received fewer services during the 12 months post-diagnosis. It is currently unclear if this is due to inferior care, overuse among white patients, or related to the clinical needs of the patients. Disclosures Schroeder: Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Vij:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansson: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Introduction: Hematopoietic cell transplantation (HCT) advances in reduced intensity conditioning, donor identification, and supportive care have led to its increased use over the last few decades. HCT is a complex process that requires coordination at multiple levels, and there may be disparities in its utilization. To better understand these access disparities, we conducted a systematic review of studies that assessed barriers to referral and/or receipt of HCT. Additionally, we focused on a subgroup of older patients (aged ≥65 at transplant), who we hypothesized would be at higher risk for access barriers to HCT. Methods: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles published in English from PubMed, Embase, Cumulative Index for Nursing and Allied Health, and Cochrane Central Register of Controlled Trials between the database inception and January 12th, 2018. Inclusion criteria were: 1) clinical trials, observational, qualitative, cross-sectional, or mixed-method study designs; 2) study assessed barriers to HCT or factors associated with referral for or receipt of HCT (except for country-specific economic factors as these are less likely to be targetable), 3) included patients ≥18 years with cancer. Narrative review articles and abstracts without full text were excluded. Two authors independently reviewed all titles and abstracts (N=3,262) and assessed studies for full-text eligibility (N=153). A third reviewer resolved any discrepancies. Eighteen studies met eligibility criteria and an additional 5 studies (not identified on our search strategy) were included on review of the bibliographies. Literature on subgroup of patients aged ≥65 was also assessed. Results: Among the 23 studies included, 16 were published after 2010. Studies were retrospective (N=18; 14 from registry data), cross-sectional (N=4; 2 from registry data), and mixed-method (N=1), and primarily conducted in the US (N=21). Barriers were assessed at the patient level (N=19; sample size ranged from 350 to 38,420), healthcare professional level (N=3; 1 study assessed both patients and healthcare professionals), or country level (N=2). Fourteen studies included some information on age of the patients and 10 studies included some patients aged 60 and above. Seventeen studies only included patients with hematologic malignancies. Age was the most common barrier identified (N=16 out of 16 studies identified older age as a barrier). Fourteen studies showed that older age was associated with lower odds of referral for or receipt of HCT, and the remaining 2 studies provided descriptive data showing lower percentages of patients receiving HCT compared to the younger age groups. Table 1 shows other potential barriers or factors associated with lower referral for or receipt of HCT at the patient, disease, physician, and organizational levels. These included race (N=14 out of 16 studies identified non-white race as a barrier), insurance or financial capacity (N=11/12), comorbidity (N=8/9), gender (N=7/17; primarily female), disease status (N=5/5), patient preferences (N=5/5), time of diagnosis (N=5/5), cancer type (N=4/6), and socioeconomic status (N=4/5). Only one study evaluated factors associated with receipt of HCT in a subgroup of patients ≥65 years. Older age, female gender, and a diagnosis of leukemia other than acute myeloid leukemia were associated with lower odds of receiving HCT. Conclusions: There are limited prospective studies evaluating access barriers to HCT in adult patients with cancer. Older age is the most commonly reported barrier to both autologous and allogeneic HCT, although studies have not addressed specific mechanisms for this disparity. In addition, other potential barriers identified such as gender, race, insurance status, and comorbidity have not been well studied in the context of older age. While some barriers may be difficult to intervene upon (e.g. comorbidity, disease status, performance status), many are amenable to interventions (e.g. socioeconomic status, distance to transplant center, social support). With the increasing trend for HCT in older patients, there is a critical need for prospective studies that better describe these access barriers and their mechanisms in order to design future interventions to reduce disparities in HCT access. Figure. Figure. Disclosures Liesveld: Onconova: Other: DSMB; Abbvie: Honoraria. Aljitawi:Medpace: Consultancy; The University of Rochester Medical Center: Patents & Royalties: Pending patent related to decellularized Wharton's jelly matrix. Klepin:Genentech Inc: Consultancy. Stock:Jazz Pharmaceuticals: Consultancy. Wildes:Janssen: Research Funding. Majhail:Incyte: Honoraria; Anthem, Inc.: Consultancy; Atara: Honoraria.

e22020Background: 20-50% of older patients (pts) with cancer have fallen in the past 6 months. Stepping On, a 7-week group-based self-management fall-prevention program addressing exercise, medicat...

10043Background: More than 60% of patients diagnosed with MM are > 65 years old and at greater risk for treatment toxicity. Comprehensive geriatric assessment predicts toxicity and survival but is ...

Background: It was once believed that African-American (AA) patients (pts) with multiple myeloma (MM) had more aggressive disease; however, recent studies suggest that undertreatment rather than biology is responsible for the poorer outcomes observed among AA pts. We recently reported that the utilization of stem cell transplants and bortezomib (BTZ) was 37% and 21% lower, respectively, among AA Medicare beneficiaries from 2000-2010 (Fiala & Wildes, Cancer, 2017). The data suggested that, had AA pts received these treatments at similar rates as their white counterparts there would have been no disparity in outcomes. As they did not, AA pts had a 10% increased risk for death. Lenalidomide (LEN), like BTZ, has become one of the primary treatments for MM since its approval in 2007. However, pts often incur significantly higher out of pocket costs on oral chemotherapies such as LEN compared to injectables like BTZ. Thus, we hypothesized that disparities in utilization of LEN would be greater than in BTZ. Methods: To test our hypothesis, all MM cases from 2007-2013 in the SEER-Medicare were reviewed along with corresponding claims through 2014. We excluded cases with incomplete records including those not enrolled in Medicare Part A, B, and D, and HMO enrollees. We also excluded cases where MM was diagnosed prior to age 65 and suspected cases of smoldering MM, pts who did not receive MM treatment and did not have diagnostic codes for CRAB criteria as previously described (Fiala, et al, under review). The presence or absence of claims for LEN and BTZ within 6 months following MM diagnosis was used to determine utilization. Multivariate logistic regression was performed to analyze the impact of race on LEN and BTZ utilization controlling for age at diagnosis, sex, year of diagnosis, Medicaid enrollment, and previously established algorithms of poor performance status [PS] indicators and Charlson Comorbidity Index [CCI] score. Results: 6,285 cases were included in the analysis. The median age at MM diagnosis was 76 years and 50% were female; 77% of cases were white, 16% were black, and 6% were another race. Overall, the utilization of LEN and BTZ during first-line treatment was 28% and 38%, respectively. In the multivariate model, race was not associated with LEN utilization, but BTZ utilization was reduced by 24% (aHR 0.76; 95% CI 0.65-0.90; p 0.0009) among AA pts. Overall, the models of LEN and BTZ were similar (Table 1). Advancing age, Medicaid enrollment and poor PS were associated with decreased utilization; more recent diagnosis increased utilization. CCI was associated with LEN but not BTZ utilization, sex with BTZ but not LEN. Discussion: We originally hypothesized that LEN utilization would be reduced among AA pts based on increased out-of-pocket costs. However, we and other researchers have shown that traditional access barriers such as insurance and income only account for about 25% of health disparities (Fiala & Wildes, Cancer, 2017). We now hypothesize LEN's oral administration may mitigate some other factors that have been shown to increase disparities such as the preferences and biases of pts and providers. For example, AA pts may prefer oral therapies to a greater extent than white pts. Or AA pts who may decline injectable chemotherapy due to distrust in the medical system may be more willing to accept an oral formulation, or providers who hold an unconscious bias may be more willing to offer one. An alternative explanation could be that AA pts, who tend to have more comorbidities and poorer overall health at MM presentation (Fiala, et al, 2015 ASH abstract 5618), were more likely to be candidates for LEN rather than other treatments. However, we do not believe this is the case as poor PS and increasing CCI were associated with decreased LEN utilization. Conclusions: AA race was associated with reduced utilization of BTZ but not LEN for first-line treatment of MM. These findings do not support our original hypothesis that LEN is associated with a greater disparity in utilization than BTZ due to the higher cost sharing involved with oral chemotherapies. Whether oral formulations mitigate other barriers to treatment such as the preferences and biases among pts and providers requires future study. Disclosures Ailawadhi: Pharmacyclics: Research Funding; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Vij: Jazz: Honoraria; Konypharma: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Abbvie: Honoraria; Janssen: Honoraria; Bristol-Meyers-Squibb: Honoraria. Wildes: Carevive Systems Inc: Consultancy; Janssen: Consultancy.

Dasatinib inhibits numerous kinases [1] including the oncogenic SRC family kinases, BCR-ABL, c-KIT, EPHA2 and the PDGFβ receptor. Overexpression or dysregulation of several kinases have been implic...

Classical Hodgkin lymphoma (cHL) is highly treatable with chemotherapy alone or combined modality therapy. High dose therapy and autologous stem cell transplant is considered standard of care for patients who relapse. For patients who relapse following transplant or who are not candidates for high dose therapy, prognosis is poor, and new treatment strategies are needed. Targeted therapies for relapsed Hodgkin lymphoma include monoclonal antibodies directed at cell surface antigens, immunoconjugates, bispecific constructs created to recruit host effector cells and radioimmunotherapy. In Epstein-Barr virus (EBV)-associated Hodgkin lymphoma, cytotoxic T lymphocytes directed at EBV antigens have been utilised in clinical trials with some success. Additionally, the immunomodulatory agents thalidomide and lenalidomide, and new classes of drugs such as the mammalian target of rapamycin inhibitors and histone deacetylase inhibitors hold promise in relapsed Hodgkin lymphoma.

High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation is a widely applied treatment for advanced non-Hodgkin lymphoma (NHL), but few studies have analyzed the tolerability and outcomes in older patients compared with younger patients treated in a homogeneous manner. We retrospectively reviewed 152 consecutive patients who underwent autologous stem cell transplantation (ASCT) following BEAM conditioning (carmustine, etoposide, cytarabine, and melphalan) for NHL from January 2000 through August 2004 at our institution. We compared 59 patients age ≥60 years and 93 patients age 20,000/mm3 were similar in younger and older patients, although days to platelet count >50,000/mm3 were longer in the older patients (median 30.0 days versus 22.5 days, P = .01). Patients over the age of 60 were more likely to develop grade III/IV mucositis than their younger counterparts (37.7% versus17.4%, P = .0063). Otherwise, the frequency of other grade III/IV toxicities were similar between younger and older patients. Treatment-related mortality (TRM) was similar between older and younger patients (8.5% versus 5.4%, P = .45). Although age was not associated with TRM, the Charlson Comorbidity Index Score was significantly correlated with TRM (P = .03). Median disease-free survival was similar between older and younger patients (21.8 months versus 29.9 months, P = .93), as was overall survival (OS) (47.7 months versus 62.5 months, P = .20). After controlling for age, the Charlson Comorbidity Index Score influenced OS [P = .013]. Overall, our cohort of patients with NHL over the age of 60 who underwent ASCT following BEAM conditioning experienced toxicities and survival similar to their younger counterparts. Comorbidities significantly influenced TRM and OS in this retrospective cohort. Future study should focus on improving tolerability of conditioning and careful prospective evaluation of comorbidities and their association with outcomes.

Hospital readmission is a common, costly problem. Little is known regarding risk factors for readmission in older adults with cancer. This study aims to identify factors associated with 30-day readmission in a cohort of older medical oncology patients.Adults age 65 and over hospitalized to an Oncology Acute Care for Elders Unit at Barnes-Jewish Hospital.Standard geriatric screening tests were administered in routine clinical care. Clinical data and 30-day readmission status were obtained through medical record review.677 patients met the inclusion criteria. 77% were white and 53% were male. Thoracic (32%), hematologic (20%), and gastrointestinal (18%) malignancies were most common. The 30-day unplanned readmission rate was 35.2%. Multivariable analyses identified complete dependence in feeding (odds ratio [OR], 3.70; 95% confidence interval [CI], 1.29-10.65), and some dependence (1.58, 1.04-2.41) and complete dependence (2.64, 1.70-4.12) in housekeeping, prior to admission, as associated with higher odds of readmission. Age75 (1.49, 1.04-2.14), African-American race (1.59, 1.06-2.39), potentially inappropriate medications (1.36, 0.94-1.99), and higher-risk reasons for index admission (1.93, 1.34-2.78) also increased odds of readmission. These factors were organized into a prognostic index.Hospital readmission was common and higher than previously reported rates in general medical populations. We identified several previously unrecognized factors associated with increased risk for readmission, including some geriatric assessment parameters, and developed a practical tool that can be used by clinicians to assess risk of 30-day readmission.

e18061 Background: Despite a favorable genetic profile, African-Americans (AAs) with mm have poorer outcomes secondary to inferior treatment. NCI-CCs provide the highest-quality of care and attendance has been associated with better outcomes in many cancers. AAs have greater access to NCI-CCs proximally; however, they attend these facilities at lower rates than their white peers. The impact of attendance at NCI-CCs on mediating racial disparities in mm outcomes has not been reported on to date. Methods: We reviewed cases of mm the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000-2011 who were enrolled in Medicare Part A and B > 1 year prior to diagnosis, excluding cases enrolled prior to age 65 and those where mm diagnosis occurred post-mortem. Any center designated a NCI-clinical or -comprehensive center in 2002, 2005, or 2010 was considered a NCI-CC; attendance was defined as 2 or more claims on separate dates (MEDPAR and Outpatient files) from a NCI-CC in the 12 months following mm diagnosis. Logistic regression was performed to determine if race was associated with attendance, Cox regression to determine the association of attendance with survival. Results: 21,843 cases were analyzed; the median age was 77 years; 80% were white, 15% AA/Black. Overall NCI-CC attendance was low, only 11% of the population. Compared to white patients, black patients had a 13% decreased odds (aOR 0.87, 95% CI 0.75-0.99) of NCI-CC attendance after controlling for age, gender, socioeconomic status, geographic, and overall health variables. Attendance was associated with a 28% decrease risk for death (aHR 0.72, 95% CI 0.68-0.76), but had little impact on black-white outcome disparities. Black patients had a 9% increase in risk (aHR 1.09, 95% CI 1.04-1.13) after controlling for NCI-CC attendance. Conclusions: Black patients with mm have lower NCI-CC attendance. This may be related to referral bias and/or patient declining referral. NCI-CC attendance was associated with superior outcomes; however, controlling for attendance did not mediate black-white outcome disparities suggesting that racial treatment disparities pervade beyond access to NCI-CCs.

e18020 Background: Older adults with myeloma (MM) have poorer survival than younger patients. NCI-CC attendance is associated with superior outcomes in many cancers. Studies show that older adults are reluctant to be treated in university settings and are more likely to be treated in the community setting. We aimed to define the factors associated with NCI-CC attendance in older adults with mm from a nationally representative sample and its association with survival. Methods: We identified all mm cases in the SEER-Medicare linked database from 2000-2011. Included cases were enrolled in Medicare Part A and B > 1 year prior to diagnosis; we excluded those enrolled at age < 65. Any center designated a NCI-clinical or -comprehensive center in 2002, 2005, or 2010 was considered an NCI-CC; attendance was defined as ≥2 separate claims from an NCI-CC in the 1-year after mm diagnosis. CM were calculated using the Charlson Comorbidity (CM) Index (CCI). Poor performance status indicators (PSi) were coded as present or absent. Logistic regression was performed to determine if age was associated with NCI-CC attendance. Cox regression was determined the association of NCI-CC attendance with survival. Results: 21,843 cases were included; median age was 77 years. Overall 10.6% of the cohort attended an NCI-CC. Increasing age was associated with decreasing NCI-CC attendance rates: 18.6% (age 65-69), 13.9% (age 70-74), 9.0% (age 75-79) and 6.0% (age ≥80). After controlling for race, gender, socioeconomic status, and urban/rural regions, increasing age, poor PSi and CCI were each associated with lower odds of NCI-CC attendance [Age: OR 0.925/year (95% CI 0.92-0.93); Poor PSi: OR 0.87 (CI 0.76-1.00); CM: 0.94/CCI point (CI 0.90-0.97)]. After controlling for sociodemographics, PS and CCI, NCI-CC attendance was associated with lower mortality [HR 0.74 (95% CI 0.70-0.78)]. Conclusions: With increasing age, poor PS indicators and CM, pts are less likely to attend an NCI-CC. After controlling for other prognostic factors, attendance at an NCI-CC was associated with lower mortality. Data from trials in older mm pts from NCI-CC or other tertiary care centers must be viewed with caveat that pts tend to have better PS and fewer CM.

10044 Background: Patients with Multiple Myeloma (MM) report some of the poorest Health-related quality of life (HRQoL). Few studies show how ASCT influences global health outcomes as measured by a Geriatric Assessment (GA). We performed a prospective GA evaluating the dynamic changes in health pre- and post-ASCT. Methods: 100 pts with plasma cell dyscrasia (median (m) = 60 yrs, range (r) = 36-75 yrs) underwent GA pre-ASCT, 90 days and 1-yr post-ASCT. GA included nutritional survey, Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), Medical Outcomes Study-Social Support Survey (MOS-SSS), Short Physical Performance Battery (SPPB), handgrip strength, self-reported Human Activity Profile (HAP) Maximum Activity Score (MAS) and Adjusted Activity Score (AAS). Data were analyzed using paired t-test (p < 0.05). Results: Pts reported moderate fatigue pre-ASCT (m = 4.6, r: 0-9.8) which normalized at 1-yr (m = 2.5, r: 0-7.3; p = 0.008). Self-reported pre-ASCT physical function (MAS) (m = 73, r = 20-94) improved at 1-yr (m = 75.5, r = 52-94; p = 0.014); AAS (m = 64, r = 18-94) also improved at 1-yr (m = 70.5, r = 38-91; p = 0.025). In contrast, MD-reported KPS decreased. Screens for deficits in anxiety, depression, social support, objective physical function, handgrip strength and wt loss did not change significantly at 1-yr. Conclusions: Our data indicate that ASCT significantly improves patient-reported fatigue and physical function, unlike MD-reported KPS. [Table: see text]

e21519 Background: Increasing age is associated with poorer outcomes in MM. However, biological aging (BA) is heterogeneous and does not correlate perfectly with chronological age (CA). A recently developed frailty of CA, functional status, and comorbidities is more predictive of toxicity, progression-free and overall survival (OS) than CA alone (Palumbo et al Blood 2015). We sought to apply the Rockwood Accumulation of Deficits approach to develop and validate a frailty index (FI) for older adults with MM. Methods: MHOS, a random survey of HRQOL (health related quality of life) in Medicare Advantage HMO enrollees, data were obtained from 1,747,042 non-cancer patients (pts) and 340 with newly diagnosed MM 1997-2011 from the SEER-MHOS linked dataset. In creating the FI, we considered only variables available throughout all 4 survey versions used since its initiation in 1998. We identified 34 variables including items related to function/mobility, comorbidities, and mental health. The FI was calculated as the number of deficits present, divided by the number total number of possible deficits, with possible scores ranging from 0 to 1 and higher values indicating more frail. Missing data points were excluded from the FI calculation. Cox regression analysis was performed to determine the association of the FI with OS, controlling for CA, gender, and race. The FI was first derived in the non-cancer cohort then applied in the MM cohort. Results: The median age was 72 for non-cancer pts and 75 for pts with MM; the median FI was 0.308 and 0.368, respectively. Among non-cancer pts, each 10% increase in FI (~3-4 more deficits) was associated with a 35% increased risk for death (aHR 1.352, 95% CI 1.350-1.354, p < 0.001); among pts with MM it was associated with a 15% increased risk (aHR 1.147, 1.065-1.236, p < 0 .001). Median OS for pts with MM in the lowest tertile of FI was 48 months (95% CI 42-56) compared to 23 months (17-33) for the highest tertile. Conclusions: Here we present a MHOS-based FI. The FI was more prognostic among non-cancer pts than among pts with MM, presumably because stage and tumor characteristics also contribute to OS in MM pts. Further exploration of the MHOS-FI in MM and other cancers is warranted.

e18127 Background: Metformin, an oral hypoglycemic agent, has been linked to favorable outcomes among patients (pts) with cancer (Coyle et al. Ann Oncol 2016). Wu et al. demonstrated better overall survival (OS) with metformin use in pts with mm and Diabetes Mellitus (DM) (Br J Cancer 2014). They also found that patient with steroid-induced DM [SID] had worse outcomes than pts with pre-existing DM [PDM]. However, Keller et al. did not find these associations in a study of VA mm pts (Blood 2015 126:4502). We evaluated the impact of DM and metformin use on outcomes of pts with mm in the SEER-Medicare database. Methods: We used SEER-Medicare claims from 2007-2013 for pts with newly diagnosed MM. DM was identified using ICD-9 codes, antidiabetic medications by Medicare part D prescription claims. Multivariate analysis was performed by Cox proportional hazard modelling to evaluate (1) Association of DM type (PDM or SID) with mm outcomes and (2) Impact of metformin on outcomes of pts with mm and DM. Covariates included age, gender, transplant, CKD (chronic kidney disease), CCI (Charlson Comorbidity Index), and use of other antidiabetic medications. Potential smoldering mm cases in the dataset were controlled for using a pre-established algorithm (Fakhri, et al,Blood 2016 128:2348) Results: Out of 4708 mm pts, 45% had DM. Among the pts with DM, 28% were on metformin. Out of the 2112 pts with DM, 20% had SID. Median follow up was 26 months. We found no association between PDM (aHR 1.04, 95% CI 0.96-1.12) or SID (aHR 1.03, 0.91-1.17) with OS when compared to non-diabetic pts. Metformin use, female gender, transplant and CCI < 5 were significantly associated with improved OS. Metformin use was associated with an 18% decrease in mortality (aHR 0.82, 0.72-0.93, p = 0.002); controlling for CKD did not impact the association (aHR 0.83 (0.73- 0.94, p = 0.005). Other antidiabetic medications including insulin were not associated with OS. Conclusions: DM (PDM or SID) and insulin use were not associated with poorer outcomes. Metformin use was associated with improved OS among pts with mm and DM in the SEER-Medicare database. The impact of metformin on outcomes in mm pts should be further investigated in prospective clinical trials.

Background: The International Staging System (ISS) for multiple myeloma (MM) is a simple risk stratification algorithm based on serum β2-microglobulin and serum albumin that identifies three patient groups with different prognoses. Recently, a revised ISS (R-ISS) has been created that combines ISS stage with serum lactate dehydrogenase (LDH) and chromosomal abnormalities (CAs) identified by fluorescence in situ hybridization (FISH); it has been shown to better stratify patients based on prognosis (Palumbo, et al, J Clin Oncol, 2015). With the increasing availability of deeper sequencing techniques, we sought to determine if the use of next generation sequencing (NGS) instead of FISH for the identification of CAs would further improve the stratification of higher-risk patients. Methods: Data was extracted from the open-access MMRF Researcher Gateway corresponding with interim analysis 8 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 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 (IMID) and/or a proteasome inhibitor (PI) for initial MM treatment; and no prior malignancies in the past 5 years. All sequencing was performed by the Translational Genomics Research Institute (TGEN). CAs were identified using custom software on long-insert whole genome sequencing data. ISS stage was calculated used β2-microglobulin and serum albumin as previously described (Greipp, et al, J Clin Oncol, 2005). R-ISS stage was then calculated as: stage I (ISS stage I, no high-risk CA, and normal LDH); stage III (ISS stage III with high-risk CAs and/or high LDH levels); stage II others. High risk CA were defined as the presence of Del(17p), t(4;14) or (4;16). High LDH was defined as LDH ≥300units/L. We performed a multivariate Cox regression analysis to compare event-free survival (EFS) defined as the interval from diagnosis to disease progression or death controlling for age (>65 vs ≤65 years) and sex for ISS, R-ISS (using FISH data), and R-ISS using NGS data (R-ISS-NGS). The level of significance was set at 0.05 for all tests. Results: 877 patients had β2-microglobulin and serum albumin available and were eligible for analysis. The median age at diagnosis was 64 years, 61% (533) were male, and 76% (666) were white. 34% (296) were ISS stage I, 36% (312) were stage II, and 31% (269) were stage 3. R-ISS was calculated on the 681 patients with available FISH and LDH data. 28% (192) were R-ISS stage I, 61% (417) were stage II, and 11% (72) were stage III. R-ISS-NGS was calculated on the 673 patients with available NGS and LDH data. 32% (212) were R-ISS-NGS stage I, 62% (414) were stage II, and 7% (47) were stage III. ISS stage was significantly associated with EFS; patients with stage II and stage III disease had an 83% (aHR 1.83 [95% CI 1.25-2.69], p = 0.0183) and 171% (aHR 2.71 [95% CI 1.85-3.95], p < 0.0001) increased risk of disease progression or death, respectively, compared to stage I patients. Using R-ISS, the model was able to better stratify patients by risk; patients with stage II and stage III disease had a 111% (aHR 2.11 [95% CI 1.32-3.37], p = 0.0017) and 360% (aHR 4.60 [95% CI 2.58-8.17], p < 0.0001) increased risk of disease progression or death, respectively, compared to stage I patients. Using, R-ISS-NGS the model was able to better stratify patients by risk particularly among stage III patients; patients with stage II and stage III disease had a 125% (aHR 2.25 [95% CI 1.42-3.55], p = 0.0005) and 470% (aHR 5.70 [95% CI 3.12-10.40], p < 0.0001) increased risk of disease progression or death, respectively, compared to stage I patients. Results are summarized in Table 1. Conclusion: R-ISS-NGS improved on FISH based R-ISS stratification, presumably due to more accurate determination of the high-risk CAs of interest. A more thorough analysis including additional candidate CAs may further increase the sensitivity of this NGS based staging system. Table 1 Table 1. Disclosures Vij: Takeda: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Karyopharma: Consultancy; Amgen: Consultancy, Research Funding; Jazz: Consultancy; Shire: Consultancy.

Background: We previously reported on a phase I dose escalation trial of CDD [carfilzomib (CFZ), pegylated liposomal doxorubicin (PLD), and dexamethasone (DEX)] (Keller, et, al, ASH 2014 Abstract 4731). The combination was well tolerated and an MTD was not reached despite administering the currently approved single-agent doses. In the maximum dose level tested, the overall response rate (ORR) was 72% (5/7) in a heavily pre-treated population. Based on the promising results of the phase I study we conducted a phase II expansion to further evaluate the efficacy of the regimen. Patient/Methods: Patients with RRMM after ≥ 1 lines of therapy, with measureable disease, and good performance status, organ function and hematological reserve were eligible. Prior CFZ or PLD/doxorubicin exposure was permitted. CFZ was given on days 1, 2, 8, 9, 15 and 16 in 28 day cycles at a dose of 56mg/m 2 , PLD on day 8 at a dose of 30mg/m 2 ,DEX on days 1, 2, 8, 9, 15 and 16 at a dose of 20mg. Following 6 cycles of combination therapy, PLD was discontinued and patients were treated with maintenance CFZ and DEX (once weekly). Response was assessed per IMWG criteria. Overall response rate (ORR) was defined as partial response (PR) or better, event-free survival as the interval from start of therapy to discontinuation. Results: Twenty-three patients were enrolled from April 2014-Mar 2016 . Median age was 63 years (range 27-70) and 52% were male. Ten patients were ISS stage 1, 6 were stage 2, and 7 were stage 3. By mSMART criteria, 1 patient was high risk and 5 were intermediate risk. Ten patients were IgG Kappa subtype; 4 had IgG Lambda subtype, 2 had IgA Kappa subtype, 2 had IgA Lambda subtype, 3 kappa light chain, and 2 lambda light chain. The median number of prior therapies was 2 (range 1-13); median time from diagnosis to start of protocol was 40 months (range 8-200). All had prior exposure to lenalidomide; 91% to bortezomib; 9% to PLD or doxorubicin; 9% to CFZ; 96% had undergone autologous transplantation. The overall response rate was 83% with 48% achieving a complete or very good partial response. The median number of cycles was 11; the median estimated event-free survival was 7.4 months at a median follow-up of 10.6 months. Five patients discontinued due to disease progression, 7 due to toxicity, 1 to proceed to a second transplant, and 10 remain on treatment at time of submission. Individual patient responses are summarized in Table 1. Grade 3/4 non-hematologic toxicity was uncommon but included: infections (11), hypertension (4), RPLS (1), and MI (1). Grade 3/4 hematologic toxicity included: thrombocytopenia (11), anemia (8), neutropenia (7), TTP (1), and hemolysis (1). Conclusion: CDD is well tolerated and efficacious in relapsed or refractory MM. The estimated ORR of the combination is 83% (95% CI 67%-98%) a notable increase compared to standard dose CFZ and DEX. Disclosures Abboud: Gerson and Lehman Group: Consultancy; Baxalta: Honoraria; Takeda: Honoraria; Novartis: Research Funding; Seattle Genetics: Research Funding; Alexion: Honoraria; Cardinal: Honoraria; Teva: Research Funding, Speakers Bureau; Pharmacyclics: Honoraria; Pfizer: Research Funding; Merck: Research Funding. DiPersio: Incyte Corporation: Research Funding. Vij: Amgen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; Shire: Consultancy; Jazz: Consultancy; Karyopharma: Consultancy; Novartis: Consultancy.

Human papilloma virus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is associated with a favourable prognosis, although approximately 20–25% of patients ultimately develop recurrent cancer. Most disease recurrence events appear within 3 years; however, long-term follow-up of reported studies are limited, and the risk of late recurrence is unknown. We present a case report of a patient who developed distant metastases of HPV-related SCC 11 years after initial diagnosis and treatment of HPV-related OPSCC. Late disease recurrence may occur after initial diagnosis of HPV-related OPSCC. This observation has implications on the appropriate duration of follow-up and surveillance of these patients.

Background Radiation treatment volumes in head and neck squamous cell carcinoma (HNSCC) are controversial. The authors report the outcomes, patterns of failure, and quality of life (QOL) of patients who received treatment for HNSCC using intensity-modulated radiation therapy (IMRT) that eliminated the treatment of contralateral retropharyngeal lymph nodes (RPLNs) in the clinically uninvolved neck. Methods A prospective institutional database was used to identify patients who had primary oral cavity, oropharyngeal, hypopharyngeal, laryngeal, and unknown primary HNSCC for which they received IMRT. There were 3 temporal groups (generations 1-3). Generation 1 received comprehensive neck IMRT with parotid sparing, generation 2 eliminated the contralateral high level II (HLII) lymph nodes, and generation 3 further eliminated the contralateral RPLNs in the clinically uninvolved neck. Patterns of failure and survival analyses were completed, and QOL data measured using the MD Anderson Dysphagia Inventory were compared in a subset of patients from generations 1 and 3. Results In total, 748 patients were identified. Of the 488 patients who received treatment in generation 2 or 3, 406 had a clinically uninvolved contralateral neck. There were no failures in the spared RPLNs (95% confidence interval, 0%-1.3%) or in the high contralateral neck (95% confidence interval, 0%-0.7%). QOL data were compared between 44 patients in generation 1 and 51 patients in generation 3. QOL improved both globally and in all domains assessed for generation 3, in which reduced radiotherapy volumes were used (P Conclusions For patients with locally advanced HNSCC, eliminating coverage to the contralateral HLII lymph nodes and contralateral RPLNs in the clinically uninvolved side of the neck is associated with minimal risk of failure in these regions and significantly improved patient-reported QOL.