Optimization of older adults by a geriatric assessment-guided multidisciplinary clinic before CAR T-cell therapy.

ABSTRACT: The optimal means of assessing candidacy of older adults (≥65 years) for chimeric antigen receptor T-cell (CAR-T) therapy 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. Sixty-one patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). A nonbinding recommendation ("proceed" or "decline") regarding suitability for CAR-T was provided for each patient based on GA results. Fifty-three patients ultimately received CAR-T (proceed, n = 47; decline, n = 6). Among patients who received B-cell maturation antigen (BCMA)-directed (n = 11) and CD19-directed CAR-T (n = 42), the median overall survival (OS) was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T therapy, with fewer impairments in those recommended "proceed." Patients recommended "proceed" had shorter median length of stay (17 vs 31 days; P = .05) and lower rates of intensive care unit admission (6% vs 50%; P = .01) than those recommended "decline." In patients receiving CD19- and BCMA-directed CAR-T therapy, a "proceed" recommendation was associated with superior OS compared with "decline" (median, 16.6 vs 11.4 months [P = .02]; and median, 16.4 vs 4.2 months [P = .03], respectively). When controlling for Karnofsky performance status, C-reactive protein, and lactate dehydrogenase at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (hazard ratio, 3.26; P = .04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes, whereas patients with high vulnerability experienced high toxicity and poor outcomes after CAR-T therapy.

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.