Tanya M. Wildes

Multiple Myeloma in the Older Adult: Better Prospects, More Challenges

PURPOSEnMultiple 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.nnnMETHODSnIn 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.nnnRESULTSnThe 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.nnnCONCLUSIONnSurvival 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.

Older adult oncology, version 2.2016: Featured updates to the NCCN guidelines

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.

Drug development for recurrent and refractory classical Hodgkin lymphoma.

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.

Time to Stop Saying Geriatric Assessment Is Too Time Consuming

Aging makes us increasingly unique. A group of older patients with cancer of identical chronologic age will demonstrate great heterogeneity with regard to vitality, comorbidity, functional status, physiologic reserves, and psychosocial functioning. Thus, age alone is an insufficient surrogate for biologic aging. Similarly, commonly used unidimensional measures, such as performance status or the American Society of Anesthesiologists classification, cannot fully do justice to this heterogeneity. Despite accumulating evidence regarding the value of geriatric assessment (GA) to encompass the diversity of older patients, it seems almost requisite in literature and presentations on GA in cancer care to state that it is too time consuming to implement in daily oncology practice. In our opinion, this complaint is ill founded and should be retired. With the imminent aging of Western societies, the number of older patients with cancer is rapidly increasing. In fact, almost 70% of the patients sitting in front of you, as a cancer specialist, will be age 65 years or older by the year 2030. This demographic shift mandates a closer look at aging-related issues that older patients face, which persist and coexist with a new cancer diagnosis. In fact, such issues may be exacerbated by cancer symptoms and treatment—for example, increased risk of falls because of chemotherapy-related neuropathy in an older adult with limited mobility. As their patient population ages, cancer specialists increasingly have to make complex treatment decisions in older patients with comorbidities and functional impairment. This requires some familiarity and experience with geriatric care components. To address this demographic development, research on the incorporation of geriatric concepts into oncologic care beganmore than 20 years ago. Cancer specialists adopted the geriatric concept of frailty—a state of decreased physiologic reserve caused by the accumulation of aging processes across multiple organ systems, which affects the patient’s resistance to stressors such as cancer or cancer therapy. In addition, the GAwas adopted for assessing the presence of impairments (eg, in cognition or mobility) and overall health status. Multiple resources now exist for oncologists wanting to implement a GA in clinical practice, such as the Web sites of the International Society of Geriatric Oncology, American Society of Clinical Oncology, Cancer and Aging Research Group, andMoffitt Cancer Center, as well as National Comprehensive Cancer Network older adult oncology guidelines. In geriatric medicine, comprehensive GA (CGA) is “a multi-dimensional, interdisciplinary, diagnostic process to identify care needs, plan care, and improve outcomes of frail older people.” CGA encompasses multiple domains beyond a traditional medical assessment, including functional status, cognition, psychological health, and socioenvironmental factors. Tailored interventions are subsequently recommended, such as nutritional supplements or home nursing to help with medications. Furthermore, an important aspect of CGA is to discuss the patient’s preferences and treatment goals so that the care plan reflects these crucial aspects of care. Although it is a time-consuming process, CGA has been proven to decrease mortality and care dependence, and is the essence of geriatric medicine. In geriatric oncology, a modified version of CGA, simply named GA, has been proposed and studied extensively in various tumor types and treatment settings. The multidimensional character has been maintained, but with a simplified process, focusing primarily on identifying health issues that may affect treatment tolerance and prognosis. In this form of GA, many of the data are collected by patient or caregiver self-report, sometimes electronically. Only certain components, including the cognitive screen and physical performance tests (eg, Timed Up and Go test), require any health care provider time. Typically, such assessments can be performed by a nurse. Estimates of the total time required are 22 to 27 minutes, with 15 to 23 minutes being completed by the patient and caregiver and only 5 to 6 minutes by the health care provider. Provided that an intervention protocol is in place, there are no differences between assessments performed by a geriatrician or a trained health care worker in the proportion of patients for whom oncologic treatment decisions are altered, nor are there differences in the use of nononcologic interventions to optimize health status. Although completion of a series of screening instruments does not allow for actual clinical diagnosis of an underlying illness, such as depression or dementia, these instruments are quick and valid methods for identifying areas that may be impaired and acquiring an overall impression of a patient’s health status. What do the data show about the utility of GA in oncology? Even in patients with a good performance status, GA can identify multiple geriatric impairments. Additionally, among older patients beginning a course of chemotherapy, GA predicts toxicity. In the Cancer and Aging Research Group model, which includes GA parameters such as mobility and falls, the lowest-risk group had a 25% rate of grade 3 to 5 toxicity, whereas the highest-risk group had an 89% risk of grade 3 to 5 toxicity. The area under the

Designing exercise clinical trials for older adults with cancer: Recommendations from 2015 Cancer and Aging Research Group NCI U13 Meeting

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.

Management of multiple myeloma in older adults: Gaining ground with geriatric assessment.

Multiple myeloma increases in incidence with age. With the aging of the population, the number of cases of multiple myeloma diagnosed in older adults each year will nearly double in the next 20years. The novel therapeutic agents have significantly improved survival in older adults, but their outcomes remain poorer than in younger patients. Older adults may be more vulnerable to toxicity of therapy, resulting in decreased dose intensity and contributing to poorer outcomes. Data are beginning to emerge to aid in identifying which individuals are at greater risk for toxicity of therapy; comorbidities, functional limitations, and age over 80years are among the factors associated with greater risk. Geriatric assessment holds promise in the care of older adults with multiple myeloma, both to allow modification of treatment to prevent toxicity, and to identify vulnerabilities that may require intervention. Emerging treatments with low toxicity and attention to individualizing therapy based on geriatric assessment may aid in further improving outcomes in older adults with multiple myeloma.

Gaps in nutritional research among older adults with cancer.

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.

A call to action in hematologic disorders: A report from the ASH scientific workshop on hematology and aging

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.

Adherence to oral cancer therapy in older adults: The International Society of Geriatric Oncology (SIOG) taskforce recommendations

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.

Personalizing Therapy for Older Adults with Lymphoid Malignancies: Options and Obstacles

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.