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.

Results from a multidisciplinary clinic guided by geriatric assessment before stem cell transplantation in older adults.

Limitations found on geriatric assessment (GA) track with worse outcomes after hematopoietic cell transplantation (HCT). We report on a multidisciplinary team clinic (MDC), consisting of a cancer-specific GA and a multidisciplinary team of providers, to assess candidacy and create an individualized optimization plan for allogeneic HCT candidates aged ≥60 years and autologous HCT and adoptive T-cell therapy candidates aged ≥70 years. Among the 247 patients evaluated in the MDC, allogeneic HCT candidates comprised the majority (60%), followed by autologous HCT (37%) with occasional older cellular therapy candidates (3%). Almost all patients meeting program-required minimum ages for MDC optimization at our institution were assessed (98%). Relative to historical control subjects undergoing GA alone, allogeneic HCT patients aged ≥60 years who underwent MDC appraisal had similar frequencies of high-risk disease, reduced intensity regimens, and high comorbidity but fewer GA-graded functional impairments. The MDC cohort experienced fewer inpatient deaths, shorter length of stay, and fewer discharges to nursing facilities compared with control subjects. Improvements in early mortality were observed over time; 1-year overall survival improved from 43% in the pre-MDC era to 70% in the recent MDC era, and 1-year nonrelapse mortality decreased from 43% to 18%. The 31 autologous HCT recipients aged ≥70 years optimized by the MDC achieved 0% nonrelapse mortality and 97% overall survival at 1 year. A GA-guided MDC for older HCT candidates is feasible and seems to reduce transplant-associated morbidity and mortality. An MDC should encourage broader and safer utilization of transplantation in older patients.

Racial and Ethnic Disparity in Symptomatic Breast Cancer Awareness despite a Recent Screen: The Role of Tumor Biology and Mammography Facility Characteristics.

BACKGROUND: In a racially and ethnically diverse sample of recently diagnosed urban patients with breast cancer, we examined associations of patient, tumor biology, and mammography facility characteristics on the probability of symptomatic discovery of their breast cancer despite a recent prior screening mammogram. METHODS: In the Breast Cancer Care in Chicago study, self-reports at interview were used to define patients as having a screen-detected breast cancer or having symptomatic awareness despite a recent screening mammogram (SADRS), in the past 1 or 2 years. Patients with symptomatic breast cancer who did not report a recent prior screen were excluded from these analyses. Characteristics associated with more aggressive disease [estrogen receptor (ER)- and progesterone receptor (PR)-negative status and higher tumor grade] were abstracted from medical records. Mammogram facility characteristics that might indicate aspects of screening quality were defined and controlled for in some analyses. RESULTS: SADRS was more common among non-Hispanic black and Hispanic than among non-Hispanic white patients (36% and 42% vs. 25%, respectively, P = 0.0004). SADRS was associated with ER/PR-negative and higher-grade disease. Patients screened at sites that relied on dedicated radiologists and sites that were breast imaging centers of excellence were less likely to report SADRS. Tumor and facility factors together accounted for two thirds of the disparity in SADRS (proportion mediated = 70%, P = 0.02). CONCLUSION: Facility resources and tumor aggressiveness explain much of the racial/ethnic disparity in symptomatic breast cancer among recently screened patients. IMPACT: A more equitable distribution of high-quality screening would ameliorate but not eliminate this disparity.

Systematic review of the efficacy of herbal galactogogues.

Exclusive breastfeeding has been linked to many positive health outcomes, yet its widespread adoption as the primary mode of providing nutrition to infants remains challenging. The most common reported reason for early breastfeeding cessation is perception of inadequate milk production. To augment breast milk production, a substantial number of women turn to herbal galactogogues despite the limited scientific evidence of their efficacy and safety. We conducted a systematic review of published literature to evaluate the efficacy of herbal galactogogues. PubMed was searched from inception to October 2012 using an iterative search process that proceeded from broad categories to specific herbs. Manuscript references were also reviewed. Only experimental studies with objective outcome measures were included. Six trials met our search criteria. Using an adapted version of the CONSORT checklist, each trial was evaluated for potential sources of bias in design and reporting. Shatavari, torbangun, fenugreek, milk thistle, and a Japanese herbal medication were the 5 herbal preparations studied. Five trials found an increase in breast milk production. Several limitations exist that affect the validity of the trial results, including small sample size, insufficient randomization methods, poorly defined eligibility criteria, use of poly-herbal interventions, and variable breastfeeding practices among enrolled subjects. Given the insufficiency of evidence from these trials, no recommendation is made for the use of herbs as galactogogues. Well-designed and well-conducted clinical trials that address the above limitations are necessary to generate a body of evidence as a basis for recommendations regarding herbal galactogogues.