Validation of Cure Assumptions when Analyzing ZUMA-7 Follow-up Data of Axicabtagene Ciloleucel and Standard of Care Therapy in Second-Line Relapsed/Refractory Large B-cell Lymphoma.

Background: ZUMA-7 is the largest randomized controlled trial (RCT) for chimeric antigen receptor (CAR) T-cell therapy, which compared axicabtagene ciloleucel (axi-cel) to historical standard of care (HSoC) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Both arms of ZUMA-7 contained potentially curative treatments; however, differences in the treatment completion rate and timing to receive definitive treatment led to differences in the extent and timing of cure. Mixture cure modeling (MCM) has been suggested as a superior method in designing and powering clinical studies of curative therapies but also for extrapolation of long-term outcomes in simulation studies.

Detection of heterogeneous resistance mechanisms to tyrosine kinase inhibitors from cell-free DNA.

Though there has been substantial progress in the development of anti-human epidermal growth factor receptor 2 (HER2) therapies to treat HER2-positive metastatic breast cancer (MBC) within the past two decades, most patients still experience disease progression and cancer-related death. HER2-directed tyrosine kinase inhibitors can be highly effective therapies for patients with HER2-positive MBC; however, an understanding of resistance mechanisms is needed to better inform treatment approaches. We performed whole-exome sequencing on 111 patients with 73 tumor biopsies and 120 cell-free DNA samples to assess mechanisms of resistance.

Bearing Witness: Témoignage as a Tool for Child Advocacy during Armed Conflict.

Children affected by armed conflict suffer devastating physical, emotional, and social harm. War uproots families, forcing many to flee as refugees or internally displaced persons, while others remain trapped in dangerous environments. In these crises, children face disproportionate risks-violence, exploitation, disrupted education, and collapsed healthcare systems.

ANK3 as a Novel Genetic Biomarker for Liafensine in Treatment-Resistant Depression: The ENLIGHTEN Randomized Clinical Trial.

Importance: This study represents a first successful use of a genetic biomarker to select potential responders in a prospective study in psychiatry. Liafensine, a triple reuptake inhibitor, may become a new precision medicine for treatment-resistant depression (TRD), a major unmet medical need.

Objective: To determine whether ANK3-positive patients with TRD benefit from a 1-mg and/or 2-mg daily oral dose of liafensine, compared with placebo, in a clinical trial.