CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma.

To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels. SIGNIFICANCE: Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial. This article is highlighted in the In This Issue feature, p. 517.

Physical Activity Behavior of Patients at a Skilled Nursing Facility: Longitudinal Cohort Study.

BACKGROUND: On-body wearable sensors have been used to predict adverse outcomes such as hospitalizations or fall, thereby enabling clinicians to develop better intervention guidelines and personalized models of care to prevent harmful outcomes. In our previous work, we introduced a generic remote patient monitoring framework (Sensing At-Risk Population) that draws on the classification of human movements using a 3-axial accelerometer and the extraction of indoor localization using Bluetooth low energy beacons, in concert. Using the same framework, this paper addresses the longitudinal analyses of a group of patients in a skilled nursing facility. We try to investigate if the metrics derived from a remote patient monitoring system comprised of physical activity and indoor localization sensors, as well as their association with therapist assessments, provide additional insight into the recovery process of patients receiving rehabilitation. OBJECTIVE: The aim of this paper is twofold: (1) to observe longitudinal changes of sensor-based physical activity and indoor localization features of patients receiving rehabilitation at a skilled nursing facility and (2) to investigate if the sensor-based longitudinal changes can complement patients' changes captured by therapist assessments over the course of rehabilitation in the skilled nursing facility. METHODS: From June 2016 to November 2017, patients were recruited after admission to a subacute rehabilitation center in Los Angeles, CA. Longitudinal cohort study of patients at a skilled nursing facility was followed over the course of 21 days. At the time of discharge from the skilled nursing facility, the patients were either readmitted to the hospital for continued care or discharged to a community setting. A longitudinal study of the physical therapy, occupational therapy, and sensor-based data assessments was performed. A generalized linear mixed model was used to find associations between functional measures with sensor-based features. Occupational therapy and physical therapy assessments were performed at the time of admission and once a week during the skilled nursing facility admission. RESULTS: Of the 110 individuals in the analytic sample with mean age of 79.4 (SD 5.9) years, 79 (72%) were female and 31 (28%) were male participants. The energy intensity of an individual while in the therapy area was positively associated with transfer activities (ß=.22; SE 0.08; P=.02). Sitting energy intensity showed positive association with transfer activities (ß=.16; SE 0.07; P=.02). Lying down energy intensity was negatively associated with hygiene activities (ß=-.27; SE 0.14; P=.04). The interaction of sitting energy intensity with time (ß=-.13; SE 0.06; P=.04) was associated with toileting activities. CONCLUSIONS: This study demonstrates that a combination of indoor localization and physical activity tracking produces a series of features, a subset of which can provide crucial information to the story line of daily and longitudinal activity patterns of patients receiving rehabilitation at a skilled nursing facility. The findings suggest that detecting physical activity changes within locations may offer some insight into better characterizing patients' progress or decline.

Risk estimation, anxiety, and breast cancer worry in women at risk for breast cancer: A single-arm trial of personalized risk communication.

OBJECTIVE: Elevated anxiety and breast cancer worry can impede mammographic screening and early breast cancer detection. Genetic advances and risk models make personalized breast cancer risk assessment and communication feasible, but it is unknown whether such communication of risk affects anxiety and disease-specific worry. We studied the effect of a personalized breast cancer screening intervention on risk perception, anxiety, and breast cancer worry. METHODS: Women with a normal mammogram but elevated risk for breast cancer (N = 122) enrolled in the Athena Breast Health risk communication program were surveyed before and after receiving a letter conveying their breast cancer risk and a breast health genetic counselor consultation. We compared breast cancer risk estimation, anxiety, and breast cancer worry before and after risk communication and evaluated the relationship of anxiety and breast cancer worry to risk estimation accuracy. RESULTS: Women substantially overestimated their lifetime breast cancer risk, and risk communication somewhat mitigated this overestimation (49% pre-intervention, 42% post-intervention, 13% Gail model risk estimate, P < .001). Both general anxiety and breast cancer worry declined significantly after risk communication in women with high baseline anxiety. Baseline anxiety and breast cancer worry were essentially unrelated to risk estimation accuracy, but risk communication increased alignment of worry with accuracy of risk assessment. CONCLUSIONS: Personalized communication about breast cancer risk was associated with modestly improved risk estimation accuracy in women with relatively low anxiety and less anxiety and breast cancer worry in women with higher anxiety. We detected no negative consequences of informing women about elevated breast cancer risk.

Implementing a Population-Based Breast Cancer Risk Assessment Program.

BACKGROUND: Personalized breast cancer risk assessment is important in identifying and managing women at increased risk for breast cancer. However, there has been little evaluation of the practical aspects of implementing a population-based program that identifies and refers high-risk patients for further evaluation. PATIENTS AND METHODS: We implemented a semiautomated approach to collect personal and family history to identify women at high risk of breast cancer. On the basis of the survey, women identified as elevated risk received letters inviting them to telephone consultations with licensed breast health genetic counselors (BHGCs). High-risk women's history was verified and counseling and referrals provided, as appropriate. RESULTS: Among 20,558 women screened, 2000 (9.7%) women were identified as high risk on the basis of patient initial report. However, most (1,580) were excluded from receiving risk communication after BHGC review of risk information with the woman or because of previous attention to breast cancer risk or an abnormal mammogram. Among 420 subjects who received risk letters, 225 received a BHGC consultation. Of these 225 women, 63 were reclassified as average risk, 158 were referred to high-risk clinics, and 5 consultations were incomplete after determining that further information was needed. Of the 158 women referred to high-risk breast clinics, 51 attended an appointment. CONCLUSION: This study highlights the complex nature of a population-based breast cancer screening program in a clinical setting and shows the substantial effort needed to identify newly discovered women at high risk for breast cancer and refer them to appropriate services.