Updated perspectives on the management of multiple myeloma in older patients: Focus on lenalidomide

Multiple myeloma is a hematologic malignancy that predominantly affects older adults, with a median age at diagnosis of 70 years old. A mainstay of multiple myeloma treatment is lenalidomide, which is an immunomodulatory drug (IMiD) that changed the treatment paradigm for multiple myeloma. This is particularly true for older adults who do not undergo autologous stem cell transplantation (ASCT). Several pivotal trials summarized in this review demonstrate the efficacy and safety of lenalidomide in older adults with multiple myeloma, including significant improvements in response rates, progression-free survival and overall survival in the first-line and relapsed/refractory settings. Potential adverse effects include venous thromboembolism, cytopenias, and second malignancies and the doses tolerated in real-world older patients are often lower than those utilized in clinical trials enrolling select older patients. Given the heterogeneity of aging, several approaches to measuring frailty have been developed and validated to aid in predicting which older adults may benefit from empiric dose reduction to reduce the risk of toxicity and improve the tolerability of treatment. A number of randomized trials have explored a range of approaches utilizing lenalidomide in older adults in both the up-front and relapsed setting, ranging from attenuated maintenance strategies through quadruplet combination therapies including proteasome inhibitors and monoclonal antibodies. This wealth of literature provides a great number of options, which can make it difficult for a clinician to determine a single optimal recommendation for an individual patient. While lenalidomide is currently part of standard of care, the treatment of multiple myeloma is growing rapidly. There is a need to expand clinical trials participation to older adults with multiple myeloma. Incorporation of validated comprehensive geriatric assessments in clinical trials for multiple myeloma could provide a more accurate depiction of the older patient population and is an area for future exploration

Loneliness, social isolation, and social support in older adults with active cancer during the COVID-19 pandemic

INTRODUCTION: The COVID-19 pandemic has had a considerable impact on mental health. The social distancing and stay-at-home orders have likely also impacted loneliness, social isolation, and social support. Older adults, particularly those with comorbidities such as cancer, have a greater potential to be impacted. Here we assessed loneliness, social isolation, and social support in older adults undergoing active cancer treatment during the pandemic. MATERIALS AND METHODS: A mixed methods study in which quantitative data and qualitative response items were collected in parallel was conducted in 100 older adults with cancer. Participants completed a survey by telephone with a series of validated questionnaires to assess the domains of loneliness, social isolation, and social support as well as several open-ended questions. Baseline demographics and geriatric assessments were summarized using descriptive statistics. Bivariate associations between social isolation and loneliness and social support and loneliness were described using Spearman correlation coefficients. Conventional content analysis was performed on the open-ended questions. RESULTS: In a population of older adults with cancer, 3% were noted to be severely lonely, although 27% percent screened positive as having at least one indicator of loneliness by the University of California, Los Angeles (UCLA) Three Item Loneliness Scale. There was a significant positive correlation between loneliness and social isolation (r = +0.52, p \u3c 0.05) as well as significant negative correlation between loneliness and social support (r = -0.49, p \u3c 0.05). There was also a significant negative correlation between loneliness and emotional support (r = -0.43, p \u3c 0.05). There was no significant association between loneliness and markers of geriatric impairments, including comorbidities, G8 score or cognition. DISCUSSION: Reassuringly, in this cohort we found relatively low rates of loneliness and social isolation and high rates of social support. Consistent with prior studies, loneliness, social isolation, and social support were found to be interrelated domains; however, they were not significantly associated with markers of geriatric impairments. Future studies are needed to study if cancer diagnosis and treatment may mediate changes in loneliness, social isolation, and social support in the context of the pandemic as well as beyond

A prospective trial comparing FDG-PET/CT and CT to assess tumor response to cetuximab in patients with incurable squamous cell carcinoma of the head and neck

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 (SUV(max)) 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 SUV(max) 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

Decision-making factors for an autologous stem cell transplant for older adults with newly diagnosed multiple myeloma: A qualitative analysis

PurposeA utologous stem cell transplant (ASCT) remains a standard of care among older adults (aged ≥65) with multiple myeloma (MM). However, heterogeneity in the eligibility and utilization of ASCT remains. We identified decision-making factors that influence ASCT eligibility and utilization among older adults with MM.MethodsA qualitative study across two academic and two community centres in Ontario was conducted between July 2019-July 2020. Older adults with MM (newly diagnosed MM aged 65-75 in whom a decision had been made about ASCT in &lt;12 months) and treating oncologists completed a baseline survey and a subsequent interview, which was analyzed using thematic analysis.ResultsEighteen patients completed the survey and 9 follow-up interviews were conducted. Patients were happy with their treatment decision with “trust in their oncologist” and “wanting the best treatment” as the most important to proceed with ASCT. “Afraid of side effects” was the most common reason for declining ASCT. Fifteen oncologists completed the survey and 10 follow-up interviews were conducted. Most relied on the ‘eye-ball’ test for ASCT eligibility over geriatric screening tools. The lack of both high-quality evidence and local guidelines impacted decision-making. Both oncologists and patients felt that chronological age alone should not affect ASCT eligibility.ConclusionWhile decision-making factors regarding ASCT can be variable, both oncologists and patients indicated that chronological age alone should not represent a barrier for ASCT among older adults. Future simplification and incorporation of ASCT eligibility geriatric assessment tools in studies as well as the inclusion of these tools in local guidelines may further improve ASCT decision-making

Cancer-specific mortality in multiple myeloma: a population-based retrospective cohort study

Survival has improved in patients diagnosed with multiple myeloma (MM) over the last two decades; however, there remains a paucity of data on the causes of death in MM patients and whether causes of death change during the disease trajectory. We conducted a retrospective population-based study to evaluate the rates of MM-specific versus non-MM cause of death and to identify factors associated with cause-specific death in MM patients, stratified into autologous stem cell transplant (ASCT) and non-ASCT cohorts. A total of 6,677 patients were included, 2,576 in the ASCT group and 4,010 in the non-ASCT group. Eight hundred and seventy-three (34%) ASCT patients and 2,787 (68%) non-ASCT patients died during the follow-up period. MM was the most frequent causes of death, causing 74% of deaths in the ASCT group and 67% in the non-ASCT group. Other cancers were the second leading causes of death, followed by cardiac and infectious diseases. Multivariable analysis demonstrated that a more recent year of diagnosis and novel agent use within 1 year of diagnosis were associated with a decreased risk of MM-specific death, whereas a history of previous non-MM cancer, older age, and the presence of CRAB criteria at diagnosis increased the risk of non-MM death. Our data suggests that despite improvement in MM outcomes in recent years, MM remains the greatest threat to overall survival for patients. Further advances in the development of effective MM therapeutic agents in both ASCT and non-ASCT populations and patient access to them is needed to improve outcomes

SIOG guidelines- essential for good clinical practice in geriatric oncology

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Postradiation Osteosarcoma in an Older Prostate Cancer Survivor: Case Study and Literature Review with Emphasis on Geriatric Principles

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

Bortezomib in first-line therapy is associated with falls in older adults with multiple myeloma

BackgroundBortezomib is a common multiple myeloma therapy that can cause treatment-related peripheral neuropathy, a risk factor for falls. The relationship between bortezomib and falls in older patients with multiple myeloma is unknown.MethodsWe analyzed the SEER-Medicare database for patients aged 65 or older diagnosed with multiple myeloma between 2007 and 2013. Claims were analyzed for myeloma treatments, falls, and covariates of interest. We evaluated accidental falls occurring within 12 months after starting first-line multiple myeloma treatment with bortezomib.ResultsBortezomib was used in first-line therapy for 2052 older adults with new diagnoses of multiple myeloma. Claims for falls were reported in 157 (8%) patients within 12 months after starting bortezomib, compared to 102 (5%) patients not receiving bortezomib (p &lt; 0.001). Bortezomib was associated with a 36% increased risk of falls after controlling for covariates (aHR 1.36; 95% CI 1.05-1.75; p = 0.018). In a landmark analysis of those who survived 12 months after starting treatment, the median overall survival of those with a fall was 35.7 months compared to 49.1 months for those without (p &lt; 0.0001). A fall in the first year after diagnosis was associated with a 26% increased risk in hazard for death (aHR 1.26; 95% CI 1.02-1.56; p = 0.033).ConclusionIn older adults with multiple myeloma, bortezomib was associated with an increased risk of having a diagnostic code for falls. Decreased overall survival was seen in those who fell within the year of starting therapy. Prospective trials involving fall assessments and fall-prevention interventions are needed in this population