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

Metastasis occurring eleven years after diagnosis of human papilloma virus-related oropharyngeal squamous cell carcinoma

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

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

Tumour boards in geriatric oncology

Multidisciplinary tumour board (MDT) is an integral part of cancer treatment planning. Although no definite survival benefits have yet been shown by mostly observational studies, other benefits of MDT have been identified. Traditionally the MDT 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 an MDT should be urgently explored

Tumour boards in geriatric oncology

Multidisciplinary tumour board (MDT) is an integral part of cancer treatment planning. Although no definite survival benefits have yet been shown by mostly observational studies, other benefits of MDT have been identified. Traditionally the MDT 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 an MDT should be urgently explored

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

Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

We previously reported that nab-paclitaxel-based induction chemotherapy (IC) and concurrent chemoradiotherapy resulted in low relapse rates (13%) and excellent survival in head and neck squamous cell carcinoma (HNSCC). We compare the disease-specific survival (DSS) and overall survival (OS) between patients given nab-paclitaxel, cisplatin, and fluorouracil with cetuximab (APF-C) and historical controls given docetaxel, cisplatin, and fluorouracil with cetuximab (TPF-C). Patients with locally advanced HNSCC were treated with APF-C (n = 30) or TPF-C (n = 38). After 3 cycles of IC, patients were scheduled to receive cisplatin concurrent with definitive radiotherapy. T and N classification and smoking history were similar between the two groups and within p16-positive and p16-negative subsets. The median duration of follow-up for living patients in the APF-C group was 43.5 (range: 30–58) months versus 52 (range: 13–84) months for TPF-C. The 2-year DSS for patients treated with APF-C was 96.7% [95% Confidence Interval (CI): 85.2%, 99.8%] and with TPF-C was 77.6% (CI: 62.6%, 89.7%) (P = 0.0004). Disease progression that resulted in death was more frequent in the TPF-C group (39%) compared with the APF-C group (3%) when adjusted for competing risks of death from other causes (Gray's test, P = 0.0004). In p16 positive OPSCC, the 2-year DSS for APF-C was 100% and for TPF-C was 74.6% (CI: 47.4%, 94.6%) (P = 0.0019) and the 2-year OS for APF-C was 94.1% (CI: 65.0%, 99.2%) and for TPF-C was 74.6% (CI: 39.8%, 91.1%) (P = 0.013). In p16 negative HNSCC, the 2-year DSS for APF-C was 91.7% (CI: 67.6%, 99.6%) and for TPF-C was 82.6% (CI: 64.4%, 94.8%) (P = 0.092). A 2-year DSS and OS were significantly better with a nab-paclitaxel-based IC regimen (APF-C) compared to a docetaxel-based IC regimen (TPF-C) in p16-positive OPSCC

Somatosensory predictors of response to pregabalin in painful chemotherapy-induced peripheral neuropathy: A randomized, placebo-controlled, crossover study

Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of a2d subunits of voltage-gated Ca21 channels, such as pregabalin, have shown efficacy in reducing mechanical sensitivity in animal models of neuropathic pain. In addition, some data suggest that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased sensitivity to pinprick. We hypothesized that greater mechanical sensitivity, as quantified by decreased mechanical pain threshold at the feet, would be predictive of a greater reduction in average daily pain in response to pregabalin vs placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600 mg per day) and placebo in crossover design. Twenty-three participants were eligible for efficacy analysis. Mechanical pain threshold was not significantly correlated with reduction in average pain (P 5 0.97) or worst pain (P 5 0.60) in response to pregabalin. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, P 5 0.23) or worst pain (29.2% vs 16.0%, P 5 0.13) from baseline. Post hoc analysis of patients with CIPN caused by oxaliplatin (n 5 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, P 5 0.04). In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN

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