Efungumab

Cryptococcal meningitis should be considered in individuals diagnosed with human immunodeficiency virus (HIV) infection and presenting with a cluster of differentiation 4 (CD4)-helper T cell count below 100 cells/ml. The 2022 guidelines from the World Health Organization (WHO) advocate for initiating treatment with a high dose (10 mg/kg) of liposomal amphotericin B, followed by flucytosine and fluconazole for a two-week duration. Additionally, alternative treatment options involving a combination of flucytosine and fluconazole are recommended. Consolidation therapy, as per the WHO guidelines, involves an eight-week course of fluconazole (800 mg), initiated after the induction phase. The dosage is then reduced to 200 mg/day, maintaining this level until the CD4 count exceeds 200 cells/mm³. Notably, the 2022 WHO guidelines prioritize a single dose of liposomal amphotericin B (LampB) over amphotericin B deoxycholate (AmpB-D) at 1 mg/kg due to its association with fewer side effects, including decreased mortality, kidney damage, and anemia. These recommendations are founded on the outcomes of the Ambisome Therapy Induction Optimization (AMBITION-CM), a multicenter, open-label, randomized controlled trial. This case report details the outpatient management of cryptococcal meningitis in a 47-year-old male with acquired immunodeficiency syndrome (AIDS) who exhibited intolerance to fluconazole. In this scenario, the decision to employ liposomal amphotericin B (LampB) as the sole agent for treatment during the outpatient phase was driven by challenges in tolerating fluconazole. Despite the absence of specific research on LampB's standalone use during the maintenance and consolidation phases, concerns regarding the patient's adverse reaction to fluconazole influenced the choice. Notably, LampB's once-weekly infusion schedule, although more expensive than AmpB-D, contributes to enhanced patient compliance. Exploring alternatives to traditional medications, such as interferon-gamma (INF-γ), Mycograb, 18B7, APX001, and T2307, holds promise in targeting novel antigens or complementing existing treatment regimens. Post-discharge, the patient received weekly LampB infusions alongside antiretroviral therapy (ART), resulting in an undetectable viral load and an increased CD4 count. A subsequent cerebrospinal fluid analysis post-discharge revealed a positive India ink stain but negative cultures for Cryptococcus, underscoring the necessity for a comprehensive and adaptable approach in managing cryptococcal meningitis.

Pimitespib (TAS-116) is the first heat shock protein 90 (HSP90) inhibitor approved in Japan, and it is indicated for the treatment of gastrointestinal stromal tumors (GIST) that have progressed after treatment with imatinib, sunitinib and regorafenib. This review describes the preclinical and clinical research with pimitespib, including its mechanism of action, pharmacokinetics, clinical antitumour activity and safety. In a phase III study, pimitespib significantly prolonged progression-free survival compared with placebo (median 2.8 vs 1.4 months; hazard ratio 0.51; 95% CI 0.30–0.87; p = 0.006). Common treatment-related adverse events were diarrhoea, decreased appetite, increase in serum creatinine, malaise, nausea and eye disorders. The efficacy and safety of pimitespib are being investigated in other tumour types and in combination with other anticancer therapies.