BRISTOL MYERS SQUIBB

Christopher Ma, Brian Feagan, Vipul Jairath, Reena Khanna, Parambir S. Dulai, and William J Sandborn disclose various financial relationships with pharmaceutical companies and research organizations, including grants, personal fees, and other forms of compensation, outside their submitted work. Robert Battat and Parambir S. Dulai report no conflict of interest.

Clostridium difficile (C. difficile) is a leading cause of hospital infections in the U.S., especially affecting the elderly, with significant health care costs. Treatment options include antibiotics like metronidazole and vancomycin, with monoclonal antibodies like bezlotoxumab showing promise in reducing recurrence. FDA approved bezlotoxumab in 2016 to lower CDI recurrence in adults.

The study analyzed costs and outcomes of lifestyle, metformin, and placebo interventions in DPP and DPPOS, focusing on direct medical, non-medical, and indirect costs from health system and societal perspectives. It found lifestyle intervention delayed diabetes onset by 11 years, was cost-saving for under 45s, and cost-effective across ages. Metformin delayed onset by 3 years, was cost-effective for younger participants but less so for older. Cost-utility analyses used QALYs, with lifestyle costing $1,124 and metformin $31,286 per QALY gained versus placebo.

A multicenter retrospective analysis evaluated combination systemic therapies in 253 nccRCC patients from 2012-2024. Results showed limited antitumor activity, with differential responses among nccRCC subsets based on regimen type. Optimal nccRCC management remains an unmet need, highlighting the necessity for further research.

LEAP-012 trial showed len + pembro + TACE significantly improved PFS vs placebo + TACE in intermediate-stage HCC patients. OS data were immature, with a trend toward improvement. Safety profiles were consistent with known effects of the treatments. OS will be reassessed in future analyses.

Glioblastoma treatment remains challenging despite advances in therapy. Immunotherapy, including vaccines, cell-based approaches, and immune checkpoint blockade, shows promise. Research indicates the CNS is immunoactive, not immunoprivileged. Clinical studies are exploring various immunotherapies, emphasizing the need for optimized response assessment and biomarkers. Combinatorial immunotherapeutic regimens are promising and require further investigation.

Myelofibrosis (MF) is a severe myeloproliferative neoplasm characterized by dysregulated JAK/STAT signaling, leading to symptoms like splenomegaly and anemia. Ruxolitinib, a JAK1/JAK2 inhibitor, is approved for MF treatment, improving spleen size and symptoms but not reversing bone marrow fibrosis. Ongoing research explores combination therapies and new agents targeting anemia and fibrosis.

CAR-T cell therapy, a groundbreaking immunotherapy, modifies patient T-cells to target and destroy cancer cells, acting as 'living drugs.' With 11 products commercialized, including 7 FDA-approved, the therapy shows promise in treating blood cancers. Challenges include expanding to solid tumors, reducing 'vein-to-vein' time, and improving reimbursement. The industry is advancing through gene-transfer techniques, partnerships, and 'on-off' switches in CAR-T cells to enhance efficacy and safety.