Optimization of Older Adults by a Geriatric Assessment-Guided Multidisciplinary Clinic Prior to CAR T-Cell Therapy.

The optimal means of assessing candidacy of older (65 years) adults for CAR T-cell therapy (CAR-T) are unknown. We explored the role of a geriatric assessment (GA)-guided multidisciplinary clinic (GA-MDC) in selecting and optimizing older adults for CAR-T. From 12/2017 - 4/2022, 61 patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). Most common diagnoses were NHL (n=42) and multiple myeloma (n=14). A non-binding recommendation ('Proceed' or 'Decline') regarding suitability for CAR-T was provided on each patient based on GA results. Fifty-three patients ultimately received CAR-T (Proceed=47, Decline=6). Among patients who received BCMA-directed (n=11) and CD19-directed (n=42) CAR-T, median OS was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T, with fewer impairments in those recommended 'Proceed'. Patients recommended 'Proceed' had shorter median length of stay (17 vs 31 days; p=0.05), lower rates of ICU admission (6% vs 50%; p=0.01) and were less likely to require rehabilitation services after discharge (11% vs 67%; p=0.01) than those recommended 'Decline'. In patients receiving CD19- and BCMA-directed CAR-T, a 'Proceed' recommendation was associated with superior OS compared to 'Decline' (median 16.6 vs 11.4 months, p=0.02 and median 16.4 vs 4.2 months, p=0.03, respectively). When controlling for Karnofsky performance status, CRP and LDH at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (HR 3.26; p=0.04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes while patients with high vulnerability experienced high toxicity and poor outcomes following CAR-T.

Cellular therapies in older adults with hematological malignancies: A case-based, state-of-the-art review.

Cellular therapies, including autologous stem cell transplant (ASCT), allogeneic hematopoietic cell transplantation (alloHCT), and chimeric antigen receptor- (CAR-) T cell therapies are essential treatment modalities for many hematological malignancies. Although their use in older adults has substantially increased within the past decades, cellular therapies represent intensive treatment approaches that exclude a large percentage of older adults due to comorbidities and frailty. Under- and overtreatment in older adults with hematologic malignancy is a challenge and many treatment decisions are influenced by chronologic age. The advent of efficient and well-tolerated newer treatment approaches for multiple myeloma has challenged the role of ASCT. In the modern era, there are no randomized clinical trials of transplant versus non-transplant strategies for patients ≥65 years. Nonetheless, ASCT is feasible for selected older patients and does not result in long-term compromise in quality of life. AlloHCT is the only curative approach for acute myeloid leukemia of intermediate and unfavourable risk but carries a significant risk for non-relapse mortality depending on comorbidities, general fitness, and transplant-specific characteristics, such as intensity of conditioning and donor choice. However, alloHCT is feasible in appropriately-selected older adults. Early referral for evaluation is strongly encouraged as this is the most obvious barrier. CAR-T cell therapies have shown unprecedented clinical efficacy and durability in relapsed and refractory diffuse large B cell lymphoma. Its use is well tolerated in older adults, although evidence comes from limited case numbers. Whether patients who are deemed unfit for ASCT qualify for CAR-T cell therapy remains elusive, but the tolerability and efficacy of CAR-T cell therapy appears promising, especially for older patients. The evidence from randomized trials is strong in favor of using a comprehensive geriatric assessment (CGA) to reduce treatment-related toxicities and guide treatment intensity in the care for solid tumors; its use for evaluation of cellular therapies is less evidence-based. However, CGA can provide useful information on patients' fitness, resilient mechanisms, and reveal potential optimization strategies for compensating for vulnerabilities. In this narrative review, we will discuss key questions on cellular therapies in older adults based on illustrative patient cases.

Androgen receptor pathway inhibitors, prostate cancer, and older adults: a global Young International Society of Geriatric Oncology drug review.

Prostate cancer is a disease of older adults that has undergone a significant therapeutic paradigm shift in the last decade with the emergence of novel androgen receptor pathway inhibitors (ARPis). One of the more commonly used ARPis is enzalutamide. This drug, along with darolutamide and apalutamide, initially received approvals in the metastatic castrate-resistant prostate cancer setting but is now utilized frequently in the metastatic castrate-sensitive and non-metastatic castration-resistant settings. Landmark phase III data illustrating ARPi efficacy in older adults are limited to those with excellent performance status. However, its role in unfit older prostate cancer patients remains to be explored in the context of a narrative review. This first-of-its-kind drug review aims to shed light on the most up-to-date evidence behind the unique toxicity profile of ARPis in the context of geriatric vulnerabilities such as cognitive and functional impairment, along with potential solutions and supporting evidence that exists to circumvent these issues in the vulnerable older adult.

Updates in the Management of Relapsed and Refractory Acute Lymphoblastic Leukemia: An Urgent Plea for New Treatments Is Being Answered!

The treatment of acute lymphoblastic leukemia (ALL) has dramatically changed over the past three decades. However, relapsed and/or refractory ALL still remains with a very low survival and high morbidity associated with its treatment. Here, we will review the outstanding progress that has been made in the treatment of relapsed and/or refractory ALL and discuss future directions and challenges that require further investigation.

The prognostic value of standardized phase angle in adults with acute leukemia: A prospective study.

Standardized phase angle (SPhA) is a tool used to estimate body composition and cell membrane integrity. Standardized phase angle has been shown to predict survival in solid malignancies and hematopoietic stem cell transplant patients. We investigated the predictive value of SPhA on 60-day mortality, overall survival (OS), and length of hospital stay (LHS) for adults with acute myelogenous and lymphoblastic leukemia (AML and ALL). Consecutive patients ≥18 years with newly diagnosed acute leukemia receiving intensive chemotherapy were enrolled. Phase angle measurements were taken on day 1 of therapy for all patients and on the day of nadir marrow for AML patients. Measurements were standardized by BMI, gender, and age to calculate the SPhA. The difference between SPhA at nadir bone marrow compared to day 1 of induction was used to calculate change in SPhA. A cutoff of 25th percentile was used to dichotomize baseline SPhA. Among 100 patients, 88% were AML, 56% were female, and mean age was 59 years. Though not statistically significant, OS by Kaplan-Meier analysis was shorter for those below the 25th percentile SPhA compared to those above (median OS: 11.0 months vs 19.5 months; P = .09). Lower baseline SPhA was associated with increased incidence of 60-day mortality in univariable (odds ratio [OR] = 5.25; 1.35, 20.44; P = .02) but not multivariable analysis (OR = 3.12; 0.67, 14.48; P = .15) adjusted for age, creatinine, and cytogenetics. Increased change in SPhA was associated with worse OS (hazard ratio = 1.15; 1.00,1.33; P = .05) in multivariable analysis. Standardized phase angle is a rapid, noninvasive, and objective measure that may be used to inform risk stratification.

Feasibility and Impact of a Student-Led, Semi-Structured, Near-Peer Student Guides Program on Navigating Through Medical School.

BACKGROUND: Mentorship is critical to developing health professionals. Near-peer mentorship pairs senior mentors with junior peers to help navigate academic, professional, and social aspects of training. METHODS: In this convergent parallel mixed methods study, we assessed the feasibility, usability, professional and social impact, and barriers to implementation of a 16-week semi-structured, near-peer, student guides program involving 39 first year medical students (MS1s) and 41 fourth year medical students (MS4s). Student enrollment was quantified, guide-guidee meetings tracked, and > 2 meetings defined as feasible. Meeting topics, impact on student advising, and barriers to sustainability were contextualized qualitatively. RESULTS: Twenty-two percent of all MS4s and 46% of MS1s enrolled in the program; 67% of guides facilitated the requisite two meetings with their group, which was less than our predetermined feasibility criteria of 75%. Most guide-guidee interactions occurred in person (91%), but text messages (82%) and video/mobile messaging apps (78%) were also used. Ninety-two percent of guidees recommended the program, and 85% were satisfied with guidance received. Barriers included meeting coordination, infrequent meetings, and informal meeting structure. CONCLUSIONS: While the program was infeasible by predefined frequency criteria, participant satisfaction was high and academic, professional, and social benefits of near-peers were reported. In response, programmatic revisions now incorporate centralized support for meetings, e-mentorship, and guide training.

Effects of Religious Involvement on HIV Management Outcomes Among HIV-Positive Adults in Central North Carolina.

OBJECTIVES: The goals of this pilot cross-sectional study were to determine the feasibility of and begin measuring the effect of religious institution affiliation on human immunodeficiency virus (HIV) clinical outcomes in the southern United States, a region marked by later initiation of antiretroviral therapy, higher HIV-related morbidity, and higher mortality rates than people living with HIV (PLWH) elsewhere in the country. It also is a region with a high density of religious institutions, which may facilitate improved health outcomes through leveraged social capital. Because spirituality is a personal construct and PLWH constitute a vulnerable population, we wanted to determine whether it would be feasible to survey patients about the topic. We hypothesized that PLWH would be willing to participate and that PLWH who report involvement in religious institutions would be more likely to have suppressed HIV viral loads (VLs) and better engagement in care than PLWH not involved in a religious institution. METHODS: Eligible participants were enrolled from the Wake Forest Infectious Diseases Specialty Clinic to complete structured interviews using validated measures of religious institution affiliation, spiritual well-being, social support, and HIV-related stigma. HIV VL and engagement in care (clinic no-show rate) data were abstracted from the electronic medical record. Descriptive statistics calculated the prevalence of religious institution involvement, outcomes of interest, and potential confounders. t Tests compared continuous outcomes assuming normality, χ2 tests compared binary outcomes, and the Wilcoxon Mann-Whitney test compared outcomes for non-normal data. RESULTS: Fifty participants completed the study (55% participation rate); 72% identified as male and 28% identified as female. A total of 48% of participants identified as black/African American and 44% identified as white. Participants who identified as men who have sex with men made up 34%. More black/African American participants than white participants reported religious institution affiliation (23%; P = 0.15). There was no statistically significant relation between religious institution affiliation and CD4 or VL; however, higher levels of social support and spiritual well-being predicted a lower clinic no-show rate (P = 0.0077 and 0.0195, respectively). There was a trend toward greater perceived HIV-related stigma and CD4 (P = 0.0845) as well as more emergency department visits (P = 0.0976). CONCLUSION: PLWH in a southern US clinic were willing to answer questions about their spirituality. Religious institution affiliation was not significantly related to virologic suppression or CD4 in this sample. Higher levels of self-reported social support (P = 0.0077) and spiritual well-being (P = 0.0195) predict better clinic attendance. These results suggest that religious affiliation alone does not imply positive benefits for all. Social support and spiritual well-being, however obtained, predict engagement in care. The next steps should include a fully powered study to define the relations among social support, spiritual well-being, and relevant clinical outcomes. Our results also support further investigation of perceived HIV-related stigma and healthcare utilization, based on the trend toward significance between emergency department visits and stigma.