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ispartof: JOURNAL OF GERIATRIC ONCOLOGY vol:10 issue:2 pages:196-198 ispartof: location:Netherlands status: published

Multiple myeloma (MM) is a disease of aging adults, and numerous therapeutic options are available for this growing demographic. MM treatment of older adults continues to evolve and includes novel combinations, new generations of targeted agents, immunotherapy, and increasing use of autologous stem cell transplantation (ASCT). Understanding age-related factors, independent of chronologic age itself, is an increasingly recognized factor in MM survivorship, especially in understudied populations, such as octogenarians. Octogenarians have inferior survival that cannot be explained by cytogenetic profiles alone. Incorporating assessments of geriatric factors can provide guidance on how to intensify or de-escalate therapeutic options. Functional status, using objective testing, is superior to traditional metrics of performance status and should be implemented to optimize the risk-benefit ratio of ASCT. ASCT is feasible and cost-effective, and chronologic age should not exclude ASCT eligibility. Upfront ASCT remains the standard of care, in the context of a sequential approach that includes pre-transplantation induction and post-transplantation maintenance. High-risk MM is classically defined by disease characteristics, yet shifting frameworks suggest that the high-risk designation could refer to any patient subgroup who is at risk for poorer outcomes—beyond disease-focused outcomes to patient-focused outcomes. Defining the optimal treatment of subgroups of older patients with high-risk disease on the basis of chromosomal abnormalities is unexplored. Here, we review tools to assess individual health status, explore vulnerability in octogenarians with MM, address ASCT decision-making, and examine high-risk MM to understand factors that contribute to survival disparities for older adults with MM.

12010 Background: Despite high prevalence of functional status (FS) and physical performance (PP) impairments among older adults with cancer, standardized assessments and interventions are not routinely used in oncology care. This study characterized how oncologist knowledge of Geriatric Assessment (GA) results influenced conversations and GA-guided recommendations addressing FS and PP concerns. Methods: Data were from a NCORP funded (UG1CA189961) nationwide cluster randomized controlled trial (ClinicalTrials.gov: NCT02107443; PI: Mohile), with inclusion criteria: age ≥70, stage III/IV solid tumor or lymphoma with palliative treatment intent, and ≥1 GA domain impairment. All subjects underwent baseline GA including standardized FS ([instrumental] activities of daily living) and PP (Timed Up and Go, Short Physical Performance Battery, Older Americans Resources and Services Physical Health scale, falls in past 6 months) measures. Oncologists in Intervention arm practices received full GA results and validated recommendations for each patient, while those in the usual care (UC) arm were only notified of depression or severe cognitive impairment. One clinical encounter per patient within 4 weeks of GA was audio-recorded, transcribed and blind coded using a priori content-analysis scheme to categorize conversations and oncologist response (dismissed, acknowledged, or addressed with recommendation) by GA domain. Frequencies, raw and adjusted (for site using generalized linear mixed models) proportions were compared using the Chi square test. Results: 541 patients (mean age: 77, range 70-96) were included. More FS and PP conversations occurred in Intervention (PP=532, FS=164) than UC (PP=183, FS=87) arm (p

12043 Background: Oral targeted therapies (OTT) have transformed the treatment landscape of Non-Hodgkin lymphoma (NHL). However, measuring, defining and optimizing adherence to OTT remains a challenge. Prior studies have reported variable adherence rates (12-100%) to OTT in cancer patients (pts), with suboptimal adherence associated with inferior outcomes. In older adults (OA), geriatric syndromes (GS) such as polypharmacy and cognitive impairment can impact adherence. While geriatric assessment (GA) can predict chemotherapy-related toxicity in OA, its utility in NHL pts on OTT is unknown. In this pilot study, we evaluate the role of GA in predicting adherence and outcomes in NHL pts on OTT. We also report the feasibility of using MEMS Cap, an electronic event monitoring system, to measure adherence in this population. Methods: Pts ≥70 years (yrs) with NHL, initiating/receiving OTT were included. A GA was performed at baseline; pt, disease, and OTT characteristics were recorded. Pts were followed monthly for the first 3 months (mos), then every 3 mos for 1 year. Primary endpoint was treatment adherence rate, measured using both subjective [brief adherence rating scale (BARS)] and objective (pill counts and MEMS cap) methods. Progression free survival (PFS) was measured from time of therapy initiation to disease progression or death. Results: Of the 54 pts screened, 25 were enrolled. Median age was 77 yrs (71-93 yrs), 21 pts had chronic lymphocytic leukemia, 3 had mantle cell lymphoma and 1 had marginal zone lymphoma. Most frequently used OTT were ibrutinib (n = 17) and venetoclax (n = 5). Most pts (72%) were on OTT at study entry. Median time on therapy was 16.4 mos (1.9-44.6 mos). GS included cognitive impairment (28%), depression (24%), polypharmacy (92%) and recent falls (12%); 48% pts had ≥2 GS. Nine pts (36%) had impaired 4-meter gait speed and/or timed-up-and-go; 20 pts (80%) had an adjusted CIRS-G score of ≥6. So far, pts have completed a median follow up of 3.3 mos. BARS was the most consistent measure of adherence used (63/63 visits, 100%). MEMS Cap and pill counts were used at 13% and 8% visits respectively. Only 5 pts used the MEMS Cap, mostly due to packaging incompatibility (44%-pill box, 32%-blister packs). Median adherence was 100% (range, 70%-100%) with no pts missing > 7 days of prescribed doses. Five pts (20%) required dose interruptions, mostly due to adverse events. Six pts discontinued therapy and 2 pts died of unrelated causes. Median PFS was not reached. Chronological age and presence of a GS were not associated with adherence rate or outcomes. Conclusions: Despite presence of ≥2 geriatric syndromes in 48% of older adults with NHL on OTT, self-reported adherence remains high ( > 99%) in this group. The MEMS Cap device has poor applicability in measuring adherence to OTT due to pill package incompatibility and increasing use of virtual/tele visits.

Importance There is currently no guidance on how to approach surveillance mammography for older breast cancer survivors, particularly when life expectancy is limited. Objective To develop expert consensus guidelines that facilitate tailored decision-making for routine surveillance mammography for breast cancer survivors 75 years or older. Evidence After a literature review of the risk of ipsilateral and contralateral breast cancer events among breast cancer survivors and the harms and benefits associated with mammography, a multidisciplinary expert panel was convened to develop consensus guidelines on surveillance mammography for breast cancer survivors 75 years or older. Using an iterative consensus-based approach, input from clinician focus groups, and critical review by the International Society for Geriatric Oncology, the guidelines were refined and finalized. Findings The literature review established a low risk for ipsilateral and contralateral breast cancer events in most older breast cancer survivors and summarized the benefits and harms associated with mammography. Draft mammography guidelines were iteratively evaluated by the expert panel and clinician focus groups, emphasizing a patient’s risk for in-breast cancer events, age, life expectancy, and personal preferences. The final consensus guidelines recommend discontinuation of routine mammography for all breast cancer survivors when life expectancy is less than 5 years, including those with a history of high-risk cancers; consideration to discontinue mammography when life expectancy is 5 to 10 years; and continuation of mammography when life expectancy is more than 10 years. Individualized, shared decision-making is encouraged to optimally tailor recommendations after weighing the benefits and harms associated with surveillance mammography and patient preferences. The panel also recommends ongoing clinical breast examinations and diagnostic mammography to evaluate clinical findings and symptoms, with reassurance for patients that these practices will continue. Conclusions and Relevance It is anticipated that these expert guidelines will enhance clinical practice by providing a framework for individualized discussions, facilitating shared decision-making regarding surveillance mammography for breast cancer survivors 75 years or older.

Background: Physical resilience, the ability to resist decline and maintain functional status despite a stressor such as chemotherapy, is a central aspect of successful aging. Understanding clinical and biological factors associated with resilience in older women receiving chemotherapy for early breast cancer may facilitate the development of targeted interventions to maintain an individual’s robustness.Methods: Women age ≥65 (N=406) with Stage I-III breast cancer who were part of a clinical study of neo/adjuvant chemotherapy in older women were recruited from 16 sites (NCT01472094, R01AG037037). The Deficit Accumulation Index (DAI), a continuous score (0-1) calculated based on 51-items from geriatric assessment data (Cohen et al Cancer 2017), was measured before and after receipt of chemotherapy. DAI was categorized as robust (0.0 12 weeks, and 74% received primary prophylaxis with WBC growth factors. Among these 324 robust older women, 253 (78%) remained robust (resilient) at the end of chemotherapy, 63 (19%) became prefrail, and 8 (3%) became frail. In univariate analyses, patients treated with anthracycline (OR=0.63, p=0.09), planned duration of treatment > 12 weeks (OR=0.56, p=0.04), elevated IL-6 ≥2.7 pg/ml (OR=0.59, p=0.05), elevated CRP ≥4.3 μg/ml (OR=0.57, p=0.04), elevated D-dimer ≥0.7 μg/ml (OR=0.61, p=0.07), or at least one elevated biomarker (OR=0.18, p Conclusions: In this cohort of older women with early breast cancer who were robust prior to initiation of chemotherapy, 22% became prefrail or frail at end of treatment. Resilience to chemotherapy was related to inflammatory and coagulation biomarkers. Further research is needed to examine the mechanism underlying why some older women are resilient and retain their robustness after receiving treatment, whereas others experience decline, and further explore the role of inflammation/coagulation in this phenomenon. Table 1. Multivariable associations between baseline blood biomarkers and resilienceResilient (n=253) No. %Non-resilient (n=71) No. %Multivariable OR (95%CI)P value# of elevated biomarkers*064 (25)4 (6)1.00190 (36)29 (41)0.16 (0.05-0.55)0.004255 (22)22 (31)0.14 (0.04-0.49)0.002344 (17)16 (23)0.14 (0.04-0.51)0.003No elevated biomarker64 (25)4 (6)1.00At least one elevated189 (75)67 (94)0.15 (0.04-0.49)0.002*Biomarkers were defined as elevated using the entire cohort median value as cut off points (IL-6 ≥2.7 pg/ml, CRP ≥4.3 μg/ml, and D-dimer ≥0.7 μg/ml). Combined effects of biomarkers were examined by creating a four-level categorical combination variable: 0=all three biomarkers are Citation Format: Mina S Sedrak, Canlan Sun, Hyman Muss, Rachel A. Freedman, Allison Magnuson, Cary P. Gross, William P. Tew, Heidi D. Klepin, Tanya M. Wildes, Efrat Dotan, Tracey O'Connor, Mary Ann Fenton, Ruby Sharma, Andrew Chapman, Cynthia Owusu, Selina Chow, Heeyoung Kim, Vani Katheria, Mark LaBarge, William Dale, Saro Armenian, Susan Neuhausen, Harvey J. Cohen. Inflammation and coagulation biomarkers associated with physical resilience in older women receiving chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-03.

Nutritional issues among older adults with cancer are an understudied area of research despite significant prognostic implications for treatment side effects, cancer-specific mortality, and overall survival. In May of 2015, the National Cancer Institute and the National Institute on Aging co-sponsored a conference focused on future directions in geriatric oncology research. Nutritional research among older adults with cancer was highlighted as a major area of concern as most nutritional cancer research has been conducted among younger adults, with limited evidence to guide the care of nutritional issues among older adults with cancer. Cancer diagnoses among older adults are increasing, and the care of the older adult with cancer is complicated due to multimorbidity, heterogeneous functional status, polypharmacy, deficits in cognitive and mental health, and several other non-cancer factors. Due to this complexity, nutritional needs are dynamic, multifaceted, and dependent on the clinical scenario. This manuscript outlines the proceedings of this conference including knowledge gaps and recommendations for future nutritional research among older adults with cancer. Three common clinical scenarios encountered by oncologists include (1) weight loss during anti-cancer therapy, (2) malnutrition during advanced disease, and (3) obesity during survivorship. In this manuscript, we provide a brief overview of relevant cancer literature within these three areas, knowledge gaps that exist, and recommendations for future research.

Background Multiple myeloma (MM) is an incurable hematological malignancy of older adults. Autologous stem cell transplant (ASCT) remains a standard of care with multiple retrospective and registry cohort studies demonstrating its efficacy in MM patients including older adults with the disease. Despite this favourable data, there remains wide heterogeneity in the utilization of ASCT, particularly among older adults with MM. We conducted a mixed methods study from the perspective of both oncologists and older adults with MM to: 1) identify decision making factors that influence ASCT eligibility and 2) to explore any barriers to ASCT utilization. Methods We conducted a mixed methods study at two academic centres and two community centres in Ontario, Canada. Older adults with MM (aged 65-75) who were within one year of treatment decision making regarding ASCT were invited to complete a survey from outpatient clinics. Oncologists (both community & academic) were recruited via email. Semi-structured interviews were conducted with all participants who agreed to an interview. Thematic analysis was conducted to identify themes from the transcripts using NVivo (qualitative analytical software). The initial 3 transcripts were independently coded by two investigators, to develop a codebook. Any discrepancies were resolved using consensual validation. Once consensus was reached, the codes were then applied to the rest of the transcripts by one coder. A convergent parallel approach was used in combining the results of the qualitative and quantitative sections of the study. Results A total of 15 oncologists and 18 patients with MM completed the surveys. Baseline patient and oncologist characteristics are listed in Table 1. The majority of patients were offered an ASCT (78%) and among those offered, 79% went ahead with ASCT. Most patients were happy with the decision to either go ahead or refuse the transplant as indicated by a low decisional regret score (median of 5 and IQR of 0-19 out of 100, with a lower score indicating less regret with the decision). With regards to oncologists, 80% stated they were aware of geriatric tools to help with treatment risk stratification; however, the majority (75%) used none of these tools and relied on the 'eye-ball' test for decision making. Nine oncologists and 9 patients completed the semi-structured interview. Summarized themes identified are shown in Figure 1. From the perspective of patients, factors that most affected ASCT decision making were: strong trusting relationship with their oncologist (n=9), family support (n=9) and wanting the best treatment available (n=6). Top reasons to refuse ASCT were: fear of not recovering to baseline (n=2) and prolonged hospital stay (n=2). Oncologists identified using their clinical judgement (n=7), the belief that transplant was the best option (n=7) and lack of medical comorbidities (n=8), as the most important factors when recommending treatment. The lack of high quality randomized controlled trial data (n=9), local guidelines (n=5) and targeted assessment tools (n=7) were identified as barriers to ASCT. Notably, both patients (n=7) and oncologists (n=7) felt that ASCT decision making should not rely on chronological age alone. The findings of the qualitative and quantitative parts of the study concurred with each other and showed similar patterns. Conclusion To our knowledge, our study is the first to analyze contextual factors from the perspective of oncologists and older adults with MM that influence ASCT decision making and utilization. Despite guidelines supporting ASCT efficacy and safety among older adults with MM, our results demonstrate that the decision to undergo ASCT in older adults with MM is complex and variable both from the perspective of the patient and oncologist. Future incorporation of patient decision aids in parallel with enrollment of older adults in ASCT clinical studies and targeted geriatric assessments tools may provide an opportunity to enhance shared decision making and local guideline developments. Disclosures McCurdy: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Sanofi: Honoraria. Wildes:Carevive Systems: Consultancy; Janssen: Research Funding; Seattle Genetics: Consultancy. Mian:Sanofi: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy; Takeda: Consultancy, Honoraria.

Context Acute myeloid leukemia (AML) has a median survival of 6-12 months, with no major improvement over the last two decades. AML is a disease of elderly patients. Less-intensive induction therapies increasingly used in older patients, presuming they are more effective/better tolerated than intensive therapies. Objective Compare survival, quality of life (QOL), and function between less-intensive versus intensive therapies. Design, Setting, and Patients We studied a retrospective cohort (n=1,295) treated from 2008-2012 at six institutions, followed by a prospective observational cohort (n=692) treated from 2013-2017 at thirteen institutions. Both cohorts were ages 18-80 years. Main outcome measures Survival estimates were obtained with the Kaplan-Meier method. We used an AML-composite model (AML-CM) assigning higher scores to increasing age, comorbidity burden, and adverse cytogenetics. Less- and more-intensive induction therapies were compared within distinct prognostic groups defined by AML-CM. We used a competing-risk Cox regression model to test the impact of allogeneic transplant (HCT). Prospective QOL and function were compared between less-intensive and intensive groups across time using logistic regression. Results 20% and 21% of patients received less-intensive therapies in the retrospective and prospective cohorts, respectively. In both cohorts, less-intensive therapies were used more often with increasing age, comorbidity burden, and cytogenetic/molecular risks, and also with Karnofsky Performance Status (KPS) ≤ 70%. Retrospective cohort patients with AML-CM scores of 4-6, 7-9, and ≥10, respectively, had significantly higher hazard ratios (HR) for death after less-intensive therapies, independent from receipt of HCT [in HCT-adjusted models, AML-CM=4-6: HR=1.82 (95% CI=1.25-2.63); =7-9: HR=1.67 (95% CI=1.22-2.27); >10: HR=1.32 (95% CI=0.99-1.72)]. Patients aged 70-79 years had similar results [HR=1.37 (95% CI=1.02-1.85), p=0.04]. Higher mortality risks were also seen in the prospective cohort after less-intensive therapies. In models adjusted for age, physician-assigned KPS and physician perceptions of chances of cure, mortality risks were similar between less-intensive and intensive therapies; QOL and function were also similar. Conclusions We did not find that receiving less-intensive induction led to better survival, QOL, or function compared to intensive therapies, including in those aged 70-79 years or with high comorbidity burden. This challenges current practice and demonstrates the need for a randomized trial. This research was, in part, funded by a Patient-Centered Outcome Research Institute award (CE-1304-7451), in part, by a Research Scholar Grant from the American Cancer Society (RSG-13-084-01-CPHPS), and, in part, supported by an American Society for Hematology Bridge Award.

Topic Significance & Study Purpose/Background/Rationale Due to advances in treatment regimens and supportive care, there are a growing number of older adults with hematologic malignancies undergoing hematopoietic cell transplant (HCT). While these advances have improved overall survival for this population, patients continue to experience rapid decline in physical, emotional, social, and role functioning post-HCT. Nursing interventions can assist with returning to life activities, an important goal for older patients. Current literature on adaptation and coping post-HCT has focused on younger survivors. The purpose of this qualitative descriptive study is to describe the experience of returning to life activities in patients 60 years of age and older who were more than three months post-HCT. Of particular interest was how coping resources and strategies help older patients adapt and cope to limitations in physical, psychological, and cognitive limitations. Methods, Intervention, & Analysis Twenty English speaking adults 60 years and older with hematological malignancy 3 to 12 months post-HCT completed semi-structured interviews. Open-ended questions and probes were guided by the Transactional Model of Stress and Coping to explore adaptive functioning, coping resources, and coping strategies. An integrated grounded theory approach was used to code the textual data to identify themes. Saturation was reached when the interview generated no new substantial information. Findings & Interpretation Eight allogeneic and twelve autologous HCT recipients participated in the interviews. Three main themes emerged from the interviews. Adaptive functioning: all participants described adapting to physical and psychological changes. Coping resources: family (95%) and the healthcare team (80%) helped participants overcome physical, psychological, and cognitive limitations. Coping strategies: participants reported using emotion-focused, problem-focused, and meaning-based coping strategies. Overall, engaging in life activities and social support were significant in the recovery of physical, psychological and cognitive function. Discussion & Implications Older HCT recipients are an understudied population at high risk for functional decline. Patient-centered information on how HCT treatment influences cognitive function, functional outcomes, and quality of life will have broad implications for patient education and development of interventions for HCT patients. The next phase of this study will use these findings to guide development of health promoting interventions that nurses and the healthcare team can implement to help HCT recipients return to life activities.

Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity (dRDI < 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion. Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI < 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI. Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide [TC] (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS < 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age >70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS < 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p < 0.001). Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged > 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS < 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population. Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-10.

Mrs. A. is a 73-year-old woman who has developed increasing fatigue and lower back pain over the past year. The pain limits her exercise tolerance such that she can now walk only 1 block. She is a retired schoolteacher who does volunteer efforts in her community but has limited her activities due to fatigue. Karnofsky performance status is 70%. She has a history of chronic hypertension treated with a diuretic, adult-onset diabetes mellitus treated with metformin, and hypothyroidism treated with levothyroxine. Initial evaluation reveals anemia, renal dysfunction, an elevated total protein, and an L2 compression fracture on lumbosacral radiographs. Results of initial and subsequent evaluation are shown below, and she is referred to a hematologist for further evaluation, which revealed the following: calcium 9.0 mg/dL, creatinine 3.2 mg/dL with estimated creatinine clearance using the Modification of Diet in Renal Disease equation of 15 mL/min, hemoglobin 9.6 g/dL, total protein 11 g/dL, albumin 3.2 g/dL, immunoglobulin A (IgA) λ M protein 6.8 g/dL, total IgA 7.2 g/dL, IgG 0.4g/dL, IgM 0.03 g/dL, free κ

The majority of patients with cancer are older adults. A comprehensive geriatric assessment (CGA) will help the clinical team identify underlying medical and functional status issues that can affect cancer treatment delivery, cancer prognosis, and treatment tolerability. The CGA, as well as more abbreviated assessments and geriatric screening tools, can aid in the treatment decision-making process through improved individualized prediction of mortality, toxicity of cancer therapy, and postoperative complications and can also help clinicians develop an integrated care plan for the older adult with cancer. In this article, we will review the latest evidence with regard to the use of CGA in oncology. In addition, we will describe the benefits of conducting a CGA and the types of interventions that can be taken by the interprofessional team to improve the treatment outcomes and well-being of older adults.

The American Society of Hematology (ASH) has recently promoted efforts to advance the intersection of hematology and aging by sponsoring an annual Scientific Friday Workshop on Hematology and Aging [1]. Hematologic disorders, both malignant and benign, are highly prevalent among older adults [2–4]. Despite the disproportionate burden of hematologic disease among older adults [2–5], research studying the implications of age across the translational spectrum remains limited older adults understudied [6–8]. The lack of pre-clinical aging models, dearth of translational efforts across diseases, and under-enrollment of older adults in clinical trials result in substantial gaps in knowledge. Understanding the interface of human aging and hematologic disorders in a growing population of older adults is warranted. Here we outline the progress to date spearheaded by the ASH community dedicated to hematology and aging.

Multiple myeloma is a malignant plasma cell disease, which typically affects older patients, with a median age at diagnosis of 70 years. The recent introduction of novel drugs and ongoing improvements in supportive care have significantly contributed to overall better management and outcomes for patients with multiple myeloma. Autologous stem-cell transplantation has been a standard part of therapy for myeloma patients for many years, first in younger patients and increasingly in older, and may still be considered in selected older patients with myeloma. In addition, in both newly diagnosed patients and in the relapsed/refractory setting, a number of novel agents tested in large phase III trials have yielded improvements in overall outcomes. As clinical trials under-enrol older patients and have stringent exclusion criteria, the data and results from them may not be generalizable to all older adults. In this review, we examine the treatment options for older adults with myeloma with a specific focus on the currently available data on novel agents in this cohort. The clinical efficacy and unique toxicity profile of each novel agent must be considered prior to the treatment plan in older adults.

BACKGROUND: Falls in older adults with cancer are common, yet factors associated with fall-risk are not well-defined and may differ from the general geriatric population. This study aims to develop and validate a model of factors associated with prior falls among older adults with cancer. METHODS: In this cross-sectional secondary analysis, two cohorts of patients aged ≥65 with cancer were examined to develop and validate a model of factors associated with falls in the prior 6 months. Potential independent variables, including demographic and laboratory data and a geriatric assessment (encompassing comorbidities, functional status, physical performance, medications and psychosocial status), were identified. A multivariate model was developed in the derivation cohort using an exhaustive modeling approach. The model selected for validation offered a low Akaike Information Criteria value and included dichotomized variables for ease of clinical use. This model was then applied in the validation cohort. RESULTS: The development cohort (N=498) had a mean age of 73 (range 65-91). Nearly one-fifth (18.2%) reported a fall in the prior 6 months. The selected model comprised 9 variables involving functional status, objective physical performance, depression, medications and renal function. The AUC of the model was 0.72 (95% confidence intervals 0.65-0.78). In the validation cohort (N=250), the prevalence of prior falls was 23.6%. The AUC of the model in the validation cohort was 0.62 (95% confidence intervals 0.51-0.71). CONCLUSION: In this study, we developed and validated a model of factors associated with prior falls in older adults with cancer. Future study is needed to examine the utility of such a model in prospectively predicting incident falls.

Objective To examine the prevalence of falls, factors associated with falls and the relationship between falls and survival in older adults with multiple myeloma. Methods In an analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare Health Outcomes Survey (MHOS)-linked database, we examined 405 older adults with multiple myeloma (MM) and 513 matched non-cancer controls. The primary outcome was self-reported within the past 12 months. Age, race, gender, symptoms, and comorbidities were self-reported in the MHOS. Survival was calculated from SEER data. Results Of the patients with MM, 171 were within 1 year of diagnosis (cohort 1) and 234 were ≥1 year postdiagnosis (cohort 2). Patients in cohorts 1 and 2 were more likely to have fallen than controls (26% and 33% vs 23%, P = .012). On multivariate analysis, among patients with myeloma (combined cohorts 1 and 2), factors associated with falls included self-report of fatigue (aOR 2.52 [95% CI 1.34-4.93]), depression (aOR 1.90 [95% CI 1.14-3.18]), or poorer general health (aOR 1.86 [95% CI 1.05-3.36]). Falls were not associated with survival. Conclusions Older adults with MM have a greater prevalence of falls than matched controls. Self-reported fatigue, depression, and poorer general health are associated with greater odds of falls.

Purpose To develop a frailty index using the Rockwood Accumulation of Deficits approach for the Medicare Health Outcomes Survey (MHOS) and apply it in a subset of older patients with newly diagnosed multiple myeloma. Methods Data from 2,692,361 patients without cancer, > 66 years of age, in SEER-MHOS linked databases between 1998 and 2009 were analyzed. A frailty index was constructed, resulting in a 25-item scale; cutoff values were created for individuals classified as frail. This frailty index was then applied to 305 patients with newly diagnosed myeloma in the database to predict overall survival. Results In the derivation cohort of patients without cancer, the median age was 74 years and the mean frailty index was 0.23 (standard deviation, 0.17). Among patients without cancer, each 10% increase in frailty index (approximately three to four more deficits) was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; 95% CI, 1.396 to 1.399; P < .001). In the cohort of patients with newly diagnosed myeloma, the median age was 76 years and the mean frailty index was 0.28 (standard deviation, 0.17). Each 10% increase in frailty index was associated with a 16% increased risk for death (adjusted hazard ratio, 1.159; 95% CI, 1.080 to 1.244; P < .001). Fifty-three percent of patients with multiple myeloma were considered frail. The estimated median overall survival of patients considered frail was 26.8 months, compared with 43.7 months ( P = .015) for those who were not. Conclusion The MHOS-based frailty index was prognostic for patients with multiple myeloma in predicting overall survival.

While anthracycline-based treatment can cure diffuse large B-cell lymphoma, most patients over age 80 do not receive doxorubicin due to toxicity concerns. This study evaluated this practice, as patients age 80 and older are largely excluded from clinical trials. The primary outcome of interest was overall survival. Secondary outcomes included treatment-related mortality and anthracycline dose intensity.We assembled a cohort of 530 newly diagnosed diffuse large B-cell lymphoma patients age 80 or older diagnosed within United States Veterans Health Administration. Treatment and survival information were obtained to determine associations between anthracycline use, dose intensity, treatment-related mortality and overall survival.Of the 530 patients, 285 received systemic treatment and 193 received an anthracycline. After controlling for potential confounders, rituximab decreased mortality (hazard ratio, 0.62; 95% confidence interval [CI]: 0.44-0.88), while doxorubicin was not significantly associated with mortality (hazard ratio, 0.87; 95% CI: 0.64-1.17). Completion of treatment with anthracycline dose intensity ≥85% of expected was only 14%. Patients treated with anthracycline dose intensity85% had better one year survival compared to those treated at ≥85% (70% vs. 59%, p=0.029).These results suggest that full dose anthracycline therapy may be less important in the treatment of diffuse large B-cell lymphoma patients over age 80. The low frequency of completion of full dose intensity treatment suggests that standard doses are an unrealistic standard of care for patients this age. Alternate treatment strategies and risk stratification should be considered for these patients.

Randomized trials showing that high-dose therapy with autologous stem cell transplant (ASCT) improved the overall survival (OS) in multiple myeloma (MM) excluded patients over age 65. To compare the outcomes of older adults with MM who underwent ASCT with non-transplant strategies, we identified 146 patients aged 65-77 with newly diagnosed MM seen in the Washington University School of Medicine from 2000 to 2010. Survival among patients who did (N=62) versus did not (N=84) undergo ASCT was compared using Cox proportional hazards modeling, controlling for comorbidities, Eastern Cooperative Oncology Group performance status (PS) and the propensity to undergo ASCT. Median age was 68 years (range 65-77). PS and comorbidities did not differ significantly between those who did versus those who did not undergo ASCT. Median OS was significantly longer in patients who underwent ASCT than in those who did not (median 56.0 months (95% confidence intervals (CIs) 49.1-65.4) versus 33.1 months (24.3-43.1), P=0.004). Adjusting for PS, comorbidities, Durie-Salmon stage and the propensity to undergo ASCT, ASCT was associated with superior OS (HR for mortality 0.52 (95% CI 0.30-0.91), P=0.02). In a cohort of older adults with MM, undergoing ASCT was associated with a nearly 50% lower mortality, after controlling for PS, comorbidities, stage and the propensity to undergo ASCT.

Population-based studies suggest that black patients with multiple myeloma (MM) have a higher mortality rate than white patients. However, other studies suggest that this disparity is related to socioeconomic status (SES) rather than race. To provide clarity on this topic, we reviewed 562 patients diagnosed with MM at our institution. Patients with high SES had a median overall survival (OS) of 62.8 months (95% confidence interval [CI] 43.1-82.6 months), compared to 53.7 months (45.2-62.3 months) and 48.6 months (40.4-56.8 months) for middle and low SES, respectively (p = 0.015). After controlling for race, age, year of diagnosis, severity of comorbidities, stem cell transplant utilization and insurance provider, patients with low SES had a 54% increase in mortality rate relative to patients with high SES. To support our findings, we performed a similar analysis of 45,505 patients with MM from the Surveillance, Epidemiology and End Results-18 (SEER) database. Low SES is independently associated with poorer OS in MM.

Age-based reduction of chemotherapy dose with the first cycle (primary dose reduction, PDR) is not routinely guideline recommended. Few studies, however, have evaluated how frequently PDR is utilized in the treatment of older patients with cancer and which factors may be associated with this decision.We conducted a secondary analysis of a multi-institutional prospective cohort study of patients age ≥65 years treated with chemotherapy. The dose and regimen were at the discretion of the treating oncologist. The prevalence of PDR and its association with treatment intent (palliative vs. curative), tumor type, patient characteristics (sociodemographics and geriatric assessment variables), and chemotherapy-associated toxicity were evaluated.Among 500 patients (mean age 73, range 65-91 years), 179 patients received curative intent chemotherapy and 321 patients received palliative intent chemotherapy, with PDR being more common in the latter sub-group (15% vs. 25%, p = 0.005). Increasing age was independently associated with PDR in both sub-groups. Comorbidity (prior cancer or liver/kidney disease) was independently associated with PDR in the palliative sub-group alone while Karnofsky Performance Status (KPS) was not associated with PDR in either subgroup. There was no significant difference in the rates of grades 3-5 toxicity, dose reductions, or delays with PDR. Patients in the palliative sub-group treated with PDR had higher rates of hospitalization compared to those treated with standard doses.PDR is more common in the palliative setting, but is also utilized among patients treated with curative intent. Factors associated with PDR include age and comorbid conditions, but not KPS.

Objectives Older adults frequently experience falls, at great cost to themselves and society. Older adults with cancer may be at greater risk for falls and have unique risk factors. Materials and methods We undertook a systematic review of the available medical literature to examine the current evidence regarding factors associated with falls in older adults with cancer. PubMed, Embase, CINAHL, CENTRAL, DARE, Cochrane Database of Systematic Reviews and clinical trials.gov were searched using standardized terms for concepts of oncology/cancer, people 60 and older, screening, falls and diagnosis. Eligible studies included cohort or case-control studies or clinical trials in which all patients, or a subgroup of patients, had a diagnosis of cancer and in which falls were either the primary or secondary outcome. Results We identified 31 studies that met our inclusion criteria. Several studies suggest that falls are more common in older adults with a diagnosis of cancer than those without. Among the 11 studies that explored factors associated with outpatient falls, some risk factors for falls established in the general population were also associated with falls in older adults with cancer, including dependence in activities of daily living and prior falls. Other factors associated with falls in a general population, such as age, polypharmacy and opioid use, were not predictive of falls among oncology populations. Falls among older adults with cancer in the inpatient setting were associated with established risk factors for falls in people without cancer, but also with factors unique to an oncology population, such as brain metastases. Conclusions Falls in older adults with cancer are more common than in the general population, and are associated with risk factors unique to people with cancer. Further study is needed to establish methods of screening older adults with cancer for fall risk and ultimately implement interventions to reduce their risk of falls. Identifying which older adults with cancer are at greater risk for falls is a requisite step to ultimately intervene and prevent falls in this vulnerable population.

Multiple myeloma (MM) is a disease of aging adults and autologous stem cell transplant (ASCT) is considered the standard of care. As the population ages a growing number of older adults will undergo ASCT and an objective approach to estimate physiologic reserve and transplant morbidity risk is warranted. Here, we evaluate assess p16INK4a (p16), a molecular aging biomarker, along with geriatric metrics to determine risk of transplant toxicity. Methods We prospectively evaluated 100 MM patients for frailty before and after ASCT using a Geriatric Assessment (GA) and collected T-cells for analysis of p16 using a custom nanostring codeset. Results Pre-transplant physical function was predicative of hospital length of stay (LOS). Each one-unit increase in physical function score, the average LOS decreased by 0.52 days (95% CI, −1.03–0.02); p = .04). Similarly, higher self-report of ADL/IADL (Human Activity Profile was associated with shorter LOS (0.65 less days (95% CI −1.15 to −0.15), p = .01). Patients with anxiety/depression (OR = 1.10 (95% CI 1.00–1.22), p = .056), lower handgrip strength (OR = 0.90 (95% CI 0.82–0.98), p = .02), falls (OR = 1.60 (95% CI 1.07–2.38), p = .02), or weight loss (OR = 5.65 (95% CI 1.17–25.24), p = .03) were more likely to be re-admitted. The estimated EFS at 1-year was 85% (95% CI, 75–91) with median follow-up of 15.7 months. Weight loss was a significant predictor of EFS (HR = 3.13 (95% CI 1.15–8.50), p = .03). Frailty assessment by self-reported fatigue minimally correlated with T-cell p16 expression (r = 0.28; p = .02). Age, Karnofsky Performance Status (KPS), or Hematopoietic cell transplantation-specific Co-Morbidity Index (HCT-CI) did not predict hospital LOS or readmissions. Conclusions Our data illustrate that a GA can identify individuals with MM who are at greater risk for morbidity following ASCT.

Multidisciplinary tumour board is an integral part of cancer treatment planning. Although no definite survival benefits have yet been shown by mostly observational studies, other benefits of multidisciplinary tumour board have been identified. Traditionally the multidisciplinary tumour board involves participation of treating clinicians-medical, radiation and surgical oncologists. They tend to focus on the cancer alone. There is an increasing awareness that the treatment goal for cancer in older adults is not primarily on prolonging survival, with functional preservation and quality of life being particularly important for this population. The use of Comprehensive Geriatric Assessment and the input of the geriatrician in informing the oncologists regarding treatment decision have increasingly been shown to be beneficial. The integration of the geriatrician into the multidisciplinary tumour board should be urgently explored.

Objectives To explore the effect of incorporating cetuximab into induction chemotherapy in locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and methods Retrospective comparative analysis of two consecutive prospective phase II trials was performed: trial 1 with nab-paclitaxel/cisplatin/5-FU and cetuximab (APF-C; n = 30) and trial 2 with APF (n = 30). Patients were scheduled to receive chemoradiation therapy (CRT) with cisplatin. T2-4 classification oropharynx (OP)/larynx/hypopharynx SCC were included. Cumulative incidence of death of disease (CIDD), overall survival (OS), and cumulative incidence of relapse were compared between APF-C and APF. Results No significant differences in patient or tumor characteristics were noted between the groups. Median follow-up of surviving patients was 52 (25–95) months. Relapse occurred in 5 (17%) patients treated with APF-C and in 2 (7%) treated with APF (p = 0.37). In human papillomavirus (HPV)-related OPSCC (n = 34), the CIDD at 52 months was 3.4% with APF-C and 2.6% with APF and the two-year OSs were 94%. In HPV-unrelated HNSCC (n = 25), the CIDD at 52 months was 4.4% with APF-C and 3.3% with APF and two-year OSs were 83% and 92%, respectively. CIDD or OS did not differ when stratified by treatment group and HPV status (CIDD: p = 0.80; OS: p = 0.30). Conclusion This exploratory retrospective comparative analysis demonstrated no significant difference in CIDD, OS, or cumulative incidence of relapse between patients treated with APF-C or APF.

There is an increasing trend towards using oral systemic therapy in patients with cancer. Compared to parenteral therapy, oral cancer agents offer convenience, have similar efficacy, and are preferred by patients, consequently making its use appealing in older adults. However, adherence is required to ensure its efficacy and to avoid compromising treatment outcomes, especially when the treatment goal is curative, or in case of symptomatic/rapidly progressing disease, where dose-intensity is important. This opens a new challenge for clinicians, as optimizing patient adherence is challenging, particularly due to lack of consensus and scarcity of available clinical evidence. This manuscript aims to review the impact of age-related factors on adherence, summarize the evidence on adherence, recommend methods for selecting patients suitable for oral cancer agents, and advise monitoring interventions to promote adherence to treatment.

Tremendous advances in the treatment of multiple myeloma have yielded improvements in survival in patients with multiple myeloma. A number of pivotal phase III trials have established the benefit of these newer agents in individuals with relapsed multiple myeloma. Because older adults are under-enrolled in clinical trials, clinical trial data may not be categorically generalizable to more vulnerable older adults. In this review, the applicability to older adults of recent clinical trials of newer agents in older adults with myeloma are examined, with attention to eligibility criteria, dosing of therapy, characteristics of the population, and subgroup analyses of older adults.

Purpose The distinction of patients with symptomatic multiple myeloma (MM) from those with smoldering MM poses a challenge for researchers who use administrative databases. Historically, researchers either have included all patients or used treatment receipt as the distinguishing factor; both methods have drawbacks. We present an algorithm for distinguishing between symptomatic and smoldering MM using ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes for the classic defining events of symptomatic MM commonly referred to as the CRAB criteria (hypercalcemia, renal impairment, anemia, and bone lesions). Patients and Methods SEER-Medicare–linked data from 4,187 patients with MM diagnosed between 2007 and 2011 were used for this analysis. Results Eighty-four percent had ICD-9-CM codes consistent with CRAB criteria, whereas only 57% received treatment. Overall survival of patients with symptomatic MM defined as receipt of treatment was 32.3 months versus 26.6 months for the overall population and 22.9 months for patients with symptomatic MM defined by CRAB criteria. Conceptually, removal of patients with smoldering MM should result in a reduction in overall survival; however, the cohort of patients who received treatment tended to be younger and healthier than the overall population, which could have skewed the results. Conclusion The algorithm we present resulted in a larger and more representative sample than classification by treatment status and reduced potential bias that could result from including all patients with smoldering MM in the analysis. Although this study was performed using the SEER-Medicare database, the methodology was broad enough that the algorithm could be extended to additional claims-based data sets with relative ease.

Summary Objectives Cetuximab, a chimeric monoclonal antibody, is the only targeted therapy approved for squamous cell carcinoma of the head and neck (SCCHN). Infusion reactions (IRs) occur in 6–18% of patients pre-medicated with diphenhydramine. Evidence for clinical risk factors for IRs is limited and the benefit of additional pre-medication to prevent IRs is unclear. Materials and methods A retrospective, single institution study of 243 SCCHN patients treated with cetuximab to evaluate potential risk factors for IRs and to assess the efficacy of additional pre-medications (nebulized albuterol and intravenous (IV) corticosteroids and/or H2-blockers) to decrease the risk of IR. Results IR (grades 1–4) and high grade (grades 3–4 only) IR occurred in 47 (19.3%) and 16 (6.6%) patients, respectively. Multivariate analysis identified Caucasian race (OR7.11, p = 0.003), medication allergy (OR3.74, p = 0.002), and blood eosinophils >3% (OR2.75, p = 0.01) independently increased the risk of IR; Caucasian race (OR5.57, p = 0.007) and medication allergy (OR4.10, p = 0.0007) increased the risk of high grade IR. IR (grades 1–4) and high grade IR occurred in 31.8% and 22.7% pre-medicated with diphenhydramine alone. Univariate analysis identified albuterol, famotidine, and corticosteroids decreased the risk of high grade IR. Furthermore, there was a significant difference between the possible combinations of the pre-medications and the risk of high grade IR by Fisher Exact test (p = 0.003) whereby the combination of albuterol, famotidine and corticosteroids was effective in preventing high grade IR. Thirty (64%) of the 47 patients who developed an IR were re-challenged and did not experience a recurrence of an IR. Conclusion These data may be used to identify patients at higher risk for cetuximab-induced IR who may be advised to not receive cetuximab or who may benefit from additional pre-medications to decrease the risk of a high grade IR.

Purpose Multiple myeloma (MM) is disproportionately diagnosed in older adults; with the aging of the population, the number of older adults diagnosed with MM will increase by nearly 80% in the next two decades. Duration of survival has improved dramatically over the last 20 years, but the improvements in older adults have not been as great as those in younger adults with MM. Methods In this article, we address treatment approaches in older adults who are eligible for and those ineligible for high-dose therapy with autologous stem-cell transplantation as well as supportive care considerations and the potential role for geriatric assessment in facilitating decision making for older adults with MM. Results The evidence from recent studies demonstrates that combinations of novel and conventional antimyeloma agents result in improved response rates and, in some cases, improved progression-free and overall survival. However, some older adults are particularly vulnerable to toxicities of therapy and discontinuation of therapy and, consequently, they have poorer survival. In addition, older adults may prioritize other outcomes of therapy, such as quality of life, over more conventional end points such as disease response and duration of survival. Geriatric assessment can facilitate risk-stratification of older adults at greater risk for adverse events from therapy and aid in personalizing therapy for vulnerable or frail older adults. Conclusion Survival in older adults with MM is improving with novel therapeutics, but efficacy must be balanced with risk of toxicity of therapy and maintenance of quality of life. Novel instruments such as geriatric assessment tools may facilitate these aims.

Computed tomography (CT), the standard method to assess tumor response to cetuximab in incurable squamous cell carcinoma of the head and neck (SCCHN), performs poorly as judged by the disparity between high disease control rate (46%) and short time to progression (TTP) (70 days). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET)/CT is an alternative method to assess tumor response. The primary objective of this prospective trial was to evaluate the metabolic response of target lesions, assessed as the change in maximum standardized uptake value (SUVmax) on FDG-PET/CT before and after 8 weeks (cycle 1) of cetuximab. Secondary objectives were to compare tumor response by CT (RECIST 1.0) and FDG-PET/CT (EORTC criteria) following cycle 1, and determine TTP with continued cetuximab administration in patients with disease control by CT after cycle 1 but stratified for disease control or progression by FDG-PET/CT. Among 27 patients, the mean percent change of SUVmax of target lesions after cycle 1 was −21% (range: +72% to −81%); by FDG-PET/CT, partial response (PR)/stable disease (SD) occurred in 15 patients (56%) and progression in 12 (44%), whereas by CT, PR/SD occurred in 20 (74%) and progression in 7 (26%). FDG-PET/CT and CT assessments were discordant in 14 patients (P = 0.0029) and had low agreement (κ = 0.30; 95% confidence interval [CI]: 0.12, 0.48). With disease control by CT after cycle 1, median TTP was 166 days (CI: 86, 217) if the FDG-PET/CT showed disease control and 105 days (CI: 66, 159) if the FDG-PET/CT showed progression (P < 0.0001). Median TTP of the seven patients whose post cycle 1 CT showed progression compared to the 12 whose FDG-PET/CT showed progression were similar (53 [CI: 49, 56] vs. 61 [CI: 50, 105] days, respectively). FDG-PET/CT may be better than CT in assessing benefit of cetuximab in incurable SCCHN.

Increasing age is both a risk factor for and a negative prognostic factor in lymphoid malignancies. The disparities in outcomes between older and younger adults with lymphoid malignancies may reflect age-related differences in treatment and in biology of disease. Lymphomas in older adults are biologically more aggressive. Only small age-related differences in the frequency of cytogenetic abnormalities are seen in multiple myeloma. No major differences in the biology of chronic lymphocytic leukemia (CCL) are seen across the age spectrum. Chemotherapy and immunotherapy in older adults with lymphoid malignancies are marked by greater vulnerability to toxicity of therapy. Excessive toxicity can result in poorer outcomes, either directly through treatment-related mortality, or through decreased dose intensity. Thus, new approaches to predict toxicity of therapy and stratified treatment algorithms based on risk of toxicity are needed. Herein we detail some of the promising approaches to predicting toxicity and tailoring treatment for older adults with lymphoid malignancies.

Hematopoietic cell transplantation (HCT) provides a life-prolonging or potentially curative treatment option for patients with hematologic malignancies. Given the high transplant-related morbidity, these treatment strategies were initially restricted to younger patients, but are increasingly being used in older adults. The incidence of most hematologic malignancies increases with age; with the aging of the population, the number of potential older candidates for HCT increases. Autologous HCT (auto-HCT) in older patients may confer a slightly increased risk of specific toxicities (such as cardiac toxicities and mucositis) and have modestly lower effectiveness (in the case of lymphoma). However, auto-HCT remains a feasible, safe, and effective therapy for selected older adults with multiple myeloma and lymphoma. Similarly, allogeneic transplant (allo-HCT) is a potential therapeutic option for selected older adults, although fewer data exist on allo-HCT in older patients. Based on currently available data, age alone is not the best predictor of toxicity and outcomes; rather, the comorbidities and functional status of the older patient are likely better predictors of toxicity than chronologic age in both the autologous and allogeneic setting. A comprehensive geriatric assessment (CGA) in older adults being considered for either an auto-HCT or allo-HCT may identify additional problems or geriatric syndromes, which may not be detected during the standard pretransplant evaluation. Further research is needed to establish the utility of CGA in predicting toxicity and to evaluate the quality of survival in older adults undergoing HCT.

BACKGROUND: The clinical benefit of nab-paclitaxel monotherapy for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) that progressed on other taxanes (cremophor-based paclitaxel or docetaxel) is unknown. METHODS: A retrospective analysis of patients treated at a single institution with nab-paclitaxel for taxane-resistant RM-HNSCC. The exploratory hypothesis was that nab-paclitaxel would result in clinical benefit (tumor response) in patients with taxane-resistant RM-HNSCC. RESULTS: Twelve patients who were treated with nab-paclitaxel monotherapy for taxane-resistant RM-HNSCC and met all eligibility criteria were identified. The majority of patients (n=9; 75%) received 3 or more lines of therapy for RM-HNSCC. All patients had platin-resistant and ten patients (83%) had cetuximab-resistant disease. Patients had RM-HNSCC that progressed on cremophor-based paclitaxel (8), docetaxel (1), or both (3). With prior taxane, the best tumor response was partial (PR) in 4 patients (33%), stable (SD) in 3 (25%), and progression in 5 (42%). The median time-to-progression (TTP) with prior taxane was 1.7 (range, 0.7–9.0) months. The median interval from last dose of taxane to first dose of nab-paclitaxel was 3 (0.7–31.3) months. With nab-paclitaxel, tumor response occurred in two patients (17%; PR in both) and disease control (PR and SD) occurred in five (42%). Median TTP with nab-paclitaxel was 2.1 months (range: 0.6–6.2) and median overall survival was 4.9 months (range: 1.9–13.5). CONCLUSION: nab-Paclitaxel provided clinical benefit in some patients with taxane-resistant RM-HNSCC. The median TTP with nab-paclitaxel and with prior taxane were similar. This exploratory observation warrants further investigation in prospective studies.

Historically, high-dose therapy in combination with autologous stem cell transplants (ASCT) for multiple myeloma (MM) was reserved for younger patients. In more recent years, the use of ASCT has expanded in the older population. However, there is still limited data on the utilization and efficacy of ASCT in older patients, particularly those over the age of 75. To further evaluate this issue, we retrospectively analyzed all patients with newly diagnosed MM between the ages of 75-78, the institutional cutoff for ASCT eligibility, that were referred to the stem cell transplant unit at our institution for consultation from the years 2012-2018. Baseline characteristics, anti-myeloma treatments, and patient outcomes were abstracted through chart review. Seventy-five patients were referred to our institution. 71% were male, 29% female. 39% patients were considered ineligible for ASCT by the consulting transplant physician. Most patients were considered transplant ineligible due to comorbidities or poor performance status. Of the 46 patients eligible for ASCT, 52% underwent the procedure during their first-line therapy. The majority of those patients received reduced intensity melphalan (140 mg/m2) while 2 patients received conventional dosing (200 mg/m2). The other 22 patients eligible for ASCT declined or elected to defer the procedure and to be treated with conventional therapy. The characteristics of these three groups were similar and are detailed in Table 1. After a median follow-up of 30 months, 25% of the patients had expired. Estimated median overall survival (OS) was 71.3 months (unable to quantitate 95% CI) for all patients. Compared to transplant eligible patients, regardless of transplant receipt, those who were transplant ineligible had a 186% increase risk for death (HR 2.86; 95% CI 1.12-7.35; p = 0.029). There was also a notable trend for longer OS in those who underwent ASCT compared to those who were eligible but declined the procedure, but it was not statistically significant (HR 0.36; 95% CI 0.10-1.28; p = 0.114). At a transplant center, two-thirds of patients referred for newly diagnosed MM between the ages 75-78 were considered eligible for ASCT and one-third underwent the procedure. Outcomes were better for patients eligible for ASCT, regardless of whether they underwent the procedure. There was also a trend for better OS in patients who underwent the procedure compared to those who declined. While small sample sizes and the retrospective nature of the study limit our ability to draw conclusions, it appears that ASCT has an OS benefit among patients age 75-78. Disclosures Fiala: Incyte: Research Funding. Stockerl-Goldstein:AbbVie: Equity Ownership; Abbott: Equity Ownership. Vij:Genentech: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Wildes:Janssen: Research Funding; Carevive: Consultancy.

Introduction Multiple myeloma (MM) is a malignant plasma cell disease with a median age at diagnosis of 70 years. Geriatric assessment and frailty measures are increasingly being utilized at the time of diagnosis for prognostication. Gait speed at baseline has recently emerged as a powerful prognostic tool which identifies frailty and predicts outcomes independent of performance status among older patients with blood cancers including myeloma (Liu et al, Blood 2019). However, the longitudinal assessment and responsiveness of change in geriatric assessment measures and functional frailty parameters, including physical performance such as gait speed, over time remains unknown. Objectives We conducted a prospective study of patients with newly diagnosed MM aged 65 and older at two institutions. The prevalence of geriatric domains at baseline has been previously published by Wildes et al (JAGS, 2019). We aimed to conduct a secondary analysis to understand the changes in geriatric and frailty assessment including physical performance as older patients underwent treatment for their myeloma. Methods Older patients with newly-diagnosed myeloma underwent a comprehensive geriatric assessment including a gait function using the Timed Up and Go test at baseline and at 6 months between the years 2012-2014. Results At baseline, forty patients were enrolled in the study with a mean age of 71.6 years; 25 (62.5%) were males. Thirty-six patients completed the 6-month follow-up with 18 patients having undergone a stem cell transplant in the interim. Overall, there were no significant change in the measured geriatric domains, including dependence, physical activity, falls, polypharmacy and cognition, at 6 months compared to baseline. Overall mental health well-being, measured with the Mental Health Inventory-17, improved over time (Table I). Physical performance, assessed with the Timed Up and Go test, showed a trend toward improvement as patients underwent treatment (11.0 seconds at the 6-month follow-up versus 12.3 at baseline, p=0.057). Additionally, two out of four individuals who were unable to complete the Timed Up and Go test at baseline were subsequently able to complete it 6 months following treatment. Conclusion Our study suggests that, for older patients with MM, treatment does not significantly lead to geriatric impairment at 6-months of follow-up, as compared to baseline and in fact is associated with improved overall mental health well-being. Additionally, both the incremental change in Timed Up and Go test and the number of individuals able to complete it may in fact improve as patients undergo treatment. This highlights that gait speed may not be static and improve with treatment, suggesting a dynamic model of frailty. Larger studies conducted longitudinally will be required to further evaluate these findings to explore the evolving concept of frailty in myeloma. Disclosures Mian: Amgen: Consultancy; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pond:Roche Canada: Employment, Other: Stock; Takeda (DSMC membership): Other: Honorarium. Tuchman:Alnylam: Honoraria, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau; Karyopharm: Honoraria; Amgen: Research Funding; Sanofi: Research Funding; Merck: Research Funding; Prothena: Research Funding; Roche: Research Funding. Fiala:Incyte: Research Funding. Wildes:Janssen: Research Funding; Carvive: Consultancy.

Introduction: DARA, a human IgGκ monoclonal antibody targeting CD38, is approved as monotherapy and in combination with standard-of-care (SoC) regimens for multiple myeloma (MM). In randomized studies, DARA-based regimens significantly improved response rates, depth of response including minimal residual disease (MRD) negativity, and progression-free survival (PFS) in NDMM and relapsed/refractory MM pts. RVd followed by high-dose therapy (HDT), autologous stem cell transplant (ASCT), and consolidation is a SoC regimen for US pts with NDMM. This phase 2, randomized study (GRIFFIN; NCT02874742) evaluated DARA plus RVd (D-RVd) in ASCT-eligible NDMM pts. A 16-pt safety run-in showed no safety concerns. Here, we present results that adding DARA to RVd improves responses rapidly, including depth of response, which increases with longer duration of therapy. Methods: Pts were randomized 1:1 to RVd ± DARA, stratified by ISS stage and creatinine clearance. Pts received 4 induction cycles, HDT, ASCT, 2 consolidation cycles, and maintenance with R ± DARA for 24 mo. During induction and consolidation (Cycles 1-6), pts received R 25 mg PO on Days 1-14; V 1.3 mg/m2 SC on Days 1, 4, 8, and 11; and d 40 mg QW every 21 days. DARA 16 mg/kg IV was given on Days 1, 8, and 15 of Cycles 1-4 and Day 1 of Cycles 5-6. During maintenance (Cycles 7-32), pts received R 10 mg (15 mg in Cycles 10+ if tolerated) on Days 1-21 every 28 days ± DARA 16 mg/kg IV Q8W (or Q4W per pt decision after Amendment 2). The primary endpoint was the stringent complete response (sCR) rate by the end of consolidation per IMWG computer algorithm. The study had 80% power to detect a 15% improvement with a 1-sided alpha of 0.1 (equivalent to 2-sided alpha of 0.2). MRD (10-5 per IMWG criteria) was assessed by next-generation sequencing (clonoSEQ; Adaptive Biotechnologies). Results: A total of 207 pts (D-RVd n = 104; RVd n =103) were randomized. Baseline demographics and disease characteristics were well balanced between arms. Median age was 60 yrs; 48%, 37%, and 14% of pts were ISS stage I, II, or III, respectively; 30 (15%) pts had high cytogenetic risk defined by FISH for del(17p), t(4;14), or t(14;16). The study met its primary endpoint; D-RVd improved the sCR rate by the end of consolidation (42.4% vs 32.0%; odds ratio 1.57; 95% CI, 0.87-2.82; 2-sided P = 0.1359); at the pre-set 2-sided alpha of 0.2. This improvement was observed in all pt subgroups except for the small subsets of ISS stage III or high-cytogenetic risk pts. Responses deepened over time (Figure); the sCR rate was 12% vs 7% with D-RVd vs RVd at the end of induction, increasing to 21% vs 14% after ASCT, and 50% vs 37% at the clinical cutoff (CCO; 13.5 mo median follow-up). D-RVd achieved higher overall response (99% vs 92%), ≥VGPR (91% vs 73%), and ≥CR (52% vs 42%) rates vs RVd by the end of consolidation. At the end of induction, 8/19 (42%) pts achieving ≥CR with D-RVd were MRD negative, compared to 1/13 (8%) pts achieving ≥CR with RVd. At the end of consolidation, 30/51 (59%) pts achieving ≥CR with D-RVd were MRD negative vs 10/41 (24%) pts achieving ≥CR with RVd. Due to the short median follow-up at CCO, PFS and OS were immature, with 6 PFS events in each arm. Median stem cell yield was 8.1 vs 9.4 × 106 cells/kg for D-RVd vs RVd. Median (range) time to platelet engraftment was 13 (2-31) and 12 (1-23) days for D-RVd vs RVd; median (range) time to neutrophil engraftment was 12 (3-31) and 12 (2-23) days for D-RVd vs RVd. Grade 3/4 TEAEs (≥10%) with D-RVd vs RVd included neutropenia (32% vs 15%), lymphopenia (23% vs 23%), thrombocytopenia (16% vs 8%), and leukopenia (15% vs 7%). There was no difference in the rate of grade 3/4 infections between arms. IRRs occurred in 41% of DARA-treated pts, which were primarily grade 1-2. Updated data will be presented. Conclusions: These data demonstrate that adding DARA to RVd significantly improves response rates and depth of response, including sCR and MRD negativity. As seen in other randomized studies, continued use of daratumumab improved depth of response. The overall safety profile of D-RVd is consistent with previous reports with DARA plus SoC. Likewise, similar to what was reported from CASSIOPEIA, stem cell mobilization and ASCT are feasible with D-RVd, without a significant effect on hematopoietic reconstitution. The study is ongoing, with pts continuing maintenance therapy. Disclosures Voorhees: BMS: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GSK: Research Funding; Novartis: Consultancy; Oncopeptides: Consultancy; Takeda: Honoraria, Research Funding; TeneBio: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria. Kaufman:Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Winship Cancer Institute of Emory University: Employment; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Consultancy; AbbVie: Consultancy; Amgen: Consultancy. Sborov:Celgene: Honoraria; Janssen: Consultancy. Reeves:Celgene: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Rodriguez:Takeda, Amgen: Consultancy, Speakers Bureau. Chari:Janssen, Celgene, Novartis Pharmaceuticals, Amgen, Bristol Myers Squibb, Pharmacyclics, Karyopharm, Sanofi, Seattle Genetics, OncoPeptides, Millenium/Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Silbermann:Janssen, Sanofi: Other: Consultant/Advisor. Costa:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Karyopharm: Consultancy; Fujimoto Pharmaceutical Corporation Japan: Other: Advisor. Anderson:Amgen, Janssen, Takeda, Celgene: Consultancy, Speakers Bureau. Shah:Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Poseida: Research Funding; Indapta Therapeutics: Equity Ownership; University of California, San Francisco: Employment; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees. Efebera:Takeda: Honoraria; Akcea: Other: Advisory board, Speakers Bureau; Janssen: Speakers Bureau. Costello:Takeda: Honoraria, Research Funding; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Jakubowiak:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; KaryoPharm Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Juno: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SkyLineDx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Wildes:Carevive: Consultancy; Janssen: Research Funding. Orlowski:BioTheryX, Spectrum Pharma: Research Funding; Bristol-Myers Squibb: 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, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kita Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ionis Pharmaceuticals; Legend Biotech; Molecular Partners; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Sanofi-Aventis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shain:Celgene: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy; Takeda: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Cowan:Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Abbvie: Research Funding; Juno: Research Funding; Sanofi: Consultancy; Cellectar: Consultancy. Murphy:Janssen: Employment, Equity Ownership. Lutska:Janssen: Employment. Pei:Janssen: Employment, Equity Ownership. Ukropec:Janssen: Employment, Equity Ownership. Vermeulen:Janssen R&D, LLC: Employment, Equity Ownership. de Boer:Janssen: Employment, Equity Ownership. Hoehn:Janssen: Employment, Equity Ownership. Lin:Janssen: Employment, Equity Ownership. Richardson:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding. OffLabel Disclosure: D-RVd is being investigated in transplant-eligible NDMM

Background: Older adults with multiple myeloma (MM) may be at increased risk for toxicity of therapy. The International Myeloma Working Group (IMWG) frailty model, which includes age, functional status, and comorbidities, accounts for the presence of toxicity. The Cancer and Aging Research Group (CARG) Toxicity Tool (Hurria et al, JCO, 2011) includes more aging-associated domains and has been well validated in older adults with solid tumors, though not in hematologic malignancies. The association between the CARG toxicity tool and toxicity of therapy in older adults with MM is unknown. The parent study tested feasibility of an electronic modified geriatric assessment (mGA) tool providing real-time results to physicians. Methods: A retrospective chart abstraction was conducted on patients from the parent study to identify all treatments prior to the GA, time on treatment after enrollment, clinical data, treatment sequencing, incidence of Grade 3-5 toxicities, dose modifications, and treatment discontinuation or new line of therapy initiated. Patients were categorized as fit, intermediate fit or frail based on the IMWG score. The CARG score, adapted to apply to MM by removal of solid tumor type and use of the Modification of Diet in Renal Disease (MDRD) equation to calculate creatinine clearance, as recommended by the International Myeloma Working Group was calculated for each patient. Results: Data was available on 100 patients from the parent study. Average age was 71.3 ± 5.4 years, 58% Male, and 75% White. 71 individual regimens were identified with 575 incidences of use. Most patients were on their 4th line of therapy (mean=3.8 ± 2.9) and 22 were not receiving treatment at the time of the GA. Patients averaged 4.5 ± 3.7 lines of therapy and 46 patients underwent autologous stem cell transplants. Mean time on treatment for 78 patients after mGA was 27.2 weeks ± 28.4 weeks. CARG scores ranged from 0 to 17 with a mean of 5.9 + 7.8. mGA results were 35.7% (n=35) fit, 39.8% (n=39) intermediate fit, and 24.5% (n=24) frail using the IMWG frailty score. There was significant correlation between mean CARG scores and fit/frailty status (p grade 3 events. Non hematologic events were less common with 38% (n=38) reporting 1 or more > grade 3 events. Incidences of hematologic and non-hematologic toxicities were not associated with CARG or IMWG frailty status. 44.9% (44 of 98) had dose modifications and 50% (49 of 98) had early therapy cessation. Conclusion: Older adults with MM are likely to require multiple lines of therapy over the course of their disease. Individualizing treatment and mitigating risk requires consistent application of geriatric assessment and toxicity tools. Our study did not find a significant association between the CARG toxicity tool, adapted for myeloma, or the IMWG frailty status. Future study will be needed to understand which patients were treated with initial dose reductions and how this impacted the risk of adverse events. Disclosures Wildes: Janssen: Research Funding; Carevive: Consultancy.

Introduction: Multiple Myeloma (MM) predominantly affects older patients, and treatment in older patients is fraught with challenges due to the spectrum of aging-associated vulnerabilities present in older patients. Age-associated cumulative decline across physiological systems results in a diminished resistance to stressors, including cancer and its treatment, creating a vulnerable state known as frailty. Frailty is associated with increased risk of adverse outcomes in patients with cancer. Identification of frailty in retrospective data, including the electronic medical record, can allow for assessment of prognosis, provide input during treatment selection and facilitate control for confounding, as in comparative effectiveness research. A frailty index (FI) operationalizes frailty using an accumulation of health-related deficits (Rockwood 2007). The deficits accumulation approach to frailty is validated in many populations and settings, including in older patients with cancer receiving chemotherapy and older adults with myeloma. Routinely collected health information in the electronic medical record system may provide a standardized and feasible means of identifying cumulative deficits and generating a FI in older adults with myeloma. The objective of this study was to develop a claims-based FI in veterans with MM. Methods: From the Veterans Administration Central Cancer Registry (VACCR), we identified all patients aged 65 years and older diagnosed with MM between 1999 and 2014. For the construction of the FI using an accumulation of health-related deficits model, we followed the method described by Orkaby et al (Orkaby, J Gerontol A Biol Sci Med Sci, 2018). The FI is calculated by dividing the total number of deficits an individual has by the total number of possible variables, giving a score between 0 and 1. We included 31 deficits in a range of systems including comorbidity, functional status, cognition, mood, sensory loss, and other geriatric domains. We categorized the FI into five groups as recommended: non-frail (FI 0-0.1), pre-frail (0.11-0.20), mild frailty (0.21-0.30), moderate frailty (0.31-0.40), and severe frailty (>0.4). We used Kaplan-Meier curves to demonstrate the relationship between frailty status and mortality in patients with MM. Next, we used cox proportional hazards regression to control for the following factors in the mortality analyses: age, BMI, race, diagnosis year, MM treatment, bisphosphonate use, and statin use. Results: We identified 3807 patients aged 65 years and older diagnosed with MM. Prior to starting treatment for MM, 28.7% of the cohort was classified as non-frail, 41.3% as pre-frail, 21.6% as mildly frail, 6.6% as moderately frail, and 1.7% as severely frail. Increasing frailty status was associated with increased mortality (Figure 1). The median overall survival for non-frail veterans was 38 months, compared to those who were pre-frail (27 months), mildly frail (15 months), moderately frail (8 months), and severely frail (9 months). After controlling for the relevant variables, higher frailty score remained significantly associated with higher mortality (Table 1). Conclusions: In this study, we demonstrate a systematic method of calculating a FI using the readily available administrative and claims data from the Electronic Medical Record in veterans with MM. Frailty status was strongly associated with mortality, independent of age, race, BMI, MM treatment, and statin use. Assessment of frailty status using the readily available electronic medical records data in retrospective data allows for assessment of prognosis. Disclosures Sanfilippo: Bristol-Myers Squibb: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Other: Travel Expenses; NHLBI: Research Funding.