ABSTRACT
The phase 3b FREEDOM trial (ClinicalTrials.gov: NCT03755518) evaluates efficacy/safety of fedratinib in intermediate- or high-risk myelofibrosis patients with platelet count ≥50 × 109/L, previously treated with ruxolitinib. The trial design included protocol specified strategies to mitigate the risk for gastrointestinal (GI) adverse events (AEs), thiamine supplementation, and encephalopathy surveillance. Due to COVID-19, accrual was cut short with 38 patients enrolled. In the efficacy evaluable population (n = 35), nine (25.7%; 95% confidence interval 12.5-43.3) patients achieved primary endpoint of ≥35% spleen volume reduction (SVR) at end of cycle (EOC) 6; and 22 (62.9%) patients showed best overall response of ≥35% SVR up to end of treatment. Sixteen (44.4%) patients showed ≥50% reduction in total symptom score at EOC6 (n = 36). Compared to previously reported JAKARTA-2 trial, rates of GI AEs were lower, and no patient developed encephalopathy. Overall, FREEDOM study showed clinically relevant spleen and symptom responses with fedratinib, and effective mitigation of GI AEs.
ABSTRACT
We report a challenging case of persistent relapsing babesiosis in an immunocompromised host that was successfully managed with atovaquone-proguanil (Malarone). Malignant B-cell transformation and immunosuppressants, such as rituximab, deplete normal B-cells which normally produce antibodies to combat Babesia infection. Treatment can be prolonged and challenging in immunocompromised hosts. Atovaquone-proguanil (Malarone) is a novel therapy that can be used as part of a salvage regimen in case antimicrobial resistance or failure exists. Weighing the risks and benefits of continuing cancer therapy treatment or reducing the level of immunosuppression may aid in treatment. These are just as important as the choice of antimicrobial therapy for effective treatment and eradication of Babesia infection, especially in immunocompromised hosts.