Magnetic Hyperthermia Therapy for High-Grade Glioma: A State-of-the-Art Review.

Magnetic hyperthermia therapy (MHT) is a re-emerging treatment modality for brain tumors where magnetic nanoparticles (MNPs) are locally delivered to the brain and then activated with an external alternating magnetic field (AMF) to generate localized heat at a site of interest. Due to the recent advancements in technology and theory surrounding the intervention, clinical and pre-clinical trials have demonstrated that MHT may enhance the effectiveness of chemotherapy and radiation therapy (RT) for the treatment of brain tumors. The future clinical success of MHT relies heavily on designing MNPs optimized for both heating and imaging, developing reliable methods for the local delivery of MNPs, and designing AMF systems with integrated magnetic particle imaging (MPI) for use in humans. However, despite the progression of technological development, the clinical progress of MHT has been underwhelming. This review aims to summarize the current state-of-the-art of MHT and offers insight into the current barriers and potential solutions for moving MHT forward.

Assessment of innate immune response modulating impurities in glucagon for injection.

Glucagon for Injection is a polypeptide hormone medication used to treat patients with severe hypoglycemia or low blood sugar. Only recently, was a generic version of glucagon for injection approved by the FDA. While the generic version was deemed equivalent to its brand-name counterpart, the two glucagon products were produced using different manufacturing processes. The brand-name glucagon is produced via recombinant DNA while the generic glucagon is produced by peptide synthesis. Different manufacturing processes can result in different levels of innate immune response modulating impurities (IIRMIs). This study utilized a cell-based assay method, which allows for detection of a broad spectrum of impurities, to investigate the IIRMI risks of the generic glucagon to make sure it has similar or less immunogenicity risks than the brand-name glucagon product. Three commercial cell lines (RAW-Blue™, HEK-Blue™-hNOD1 and HEK-Blue™-hNOD2) carrying a secreted embryonic alkaline phosphatase reporter construct were used to quantify the level of innate immune responses after being treated with the glucagon drugs. The study results showed that despite differences in manufacturing process, the innate immunogenicity risk in the synthetic (generic) glucagon was at negligible level and comparable to the recombinant (brand-name) glucagon product.

Phase Ib trial of lenalidomide as post-remission therapy for older adults with acute myeloid leukemia: Safety and longitudinal assessment of geriatric functional domains.

BACKGROUND AND OBJECTIVES: Novel, non-cytotoxic agents are driving a paradigm shift for treatment of older adults with acute myeloid leukemia (AML). Older patients who initially receive intensive cytotoxic induction may choose to not proceed with cytotoxic consolidation therapy. Lenalidomide is an orally-administered immunomodulatory small molecule with activity in AML and a favorable safety profile in older adults with active leukemia. We conducted a phase Ib study of lenalidomide as post-remission therapy in older adults and assessed its impact on geriatric functional domains. MATERIALS AND METHODS: Participants were patients with AML over age 60 years who had undergone induction therapy and were poor candidates for cytotoxic consolidation. Lenalidomide was administered for 28 days in three dose cohorts. A Bayesian dose-escalation method determined cohort assignment and maximum tolerated dose (MTD). Geriatric assessment (GA) was performed before and after the cycle of lenalidomide. RESULTS: Nineteen patients with median age 68 were treated with at least one 28-day course of lenalidomide. Dose-limiting toxicities were observed in three participants at 25 mg, zero participants at 35 mg, and one participant at 50 mg. MTD was 35 mg. Median relapse-free survival was 4.3 months. GA was completed before and after treatment in fifteen patients, demonstrating improved cognitive function and no changes in physical, psychological, or social function after lenalidomide. CONCLUSION: Lenalidomide can be safely administered to older adults with AML with preservation of functional domains important to older patients. Serial GA can be performed in a novel drug study as a tool to characterize treatment tolerability.