FIP1L1-PDGFRA fusion

Prednisolone improved systemic symptoms, but temporal arteritis relapsed during tapering and was refractory to methotrexate. The addition of mepolizumab achieved sustained remission and enabled further glucocorticoid (GC) reduction. This case highlights that bilateral or GC-dependent eosinophilic temporal arteritis warrants evaluation for systemic eosinophilic disorders, and suggests that IL-5 blockade can be an effective GC-sparing strategy in HES.

The patient was treated with corticosteroids, anticoagulation, and Imatinib...Recognizing molecularly driven eosinophilic disorders is essential, as targeted treatment can significantly improve prognosis. The presence of the Fip1-Like1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRα) fusion gene is a rare cause of hypereosinophilic syndrome requiring a distinct therapeutic approach.

Treatment with low-dose imatinib (100 mg daily) and enoxaparin resulted in rapid normalization of eosinophil counts and reduction in thrombus size. This case highlights the importance of recognizing eosinophil-associated cardiac and neurologic complications and underscores the diagnostic and therapeutic value of molecular testing in patients with unexplained stroke and eosinophilia.

P3, N=134, Active, not recruiting, AstraZeneca | Trial completion date: Sep 2026 --> Dec 2026

We sequenced genomic DNA from patients (n = 20) with a known or suspected TK gene fusion and identified rearrangements in 18 cases, including all cases with a known TK fusion, typical and atypical BCR::ABL1 rearrangements, an 843Kb deletion causing a FIP1L1::PDGFRA fusion, novel AGAP2::PDGFRB and NFIA::PDGFRB fusions, and a complex CCDC88C::PDGFRB rearrangement with multiple translocation events. The approach was fast (<72 h/sample from DNA to result), flexible with minimal hands-on laboratory time, and provided accurate, patient-specific characterisation of genomic breakpoints.

Meanwhile, the FIP1L1::PDGFRA fusion gene detection results strongly support the use of molecular diagnosis in ABL. In addition, the patient successfully achieved a complete response to treatment and was followed for a year and a half without relapse, thus offering valuable insights for treatment strategies in similar cases.

Case 6 experienced symptom relief after glucocorticoids and hydroxyurea treatment, followed by complete remission after chemotherapy with the cytarabine (20 mg q12 h × 14 days), idarubicin (5 mg on days 2-12 every other day), and G-CSF (adjusted based on blood counts) regimen. The remaining three patients demonstrated improvement after glucocorticoid treatment. Except for case 6, the other patients were still alive, with case 4 relapsing at 28 months after imatinib discontinuation and relieved after treatment re-initiation.

P3, N=134, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2027 --> Sep 2026

The findings highlight the importance of accurate classification and tailored management of HE and HES, which are crucial for preventing organ damage and improving quality of life. Ongoing clinical trials and research will expand therapeutic options, clarify underlying mechanisms, and address current unmet needs.

This case highlights that Loeffler endocarditis can present as the primary and sole manifestation of chronic eosinophilic leukaemia. Effective collaboration between cardiologists and internists is crucial for timely diagnosis and comprehensive management, ultimately resulting in enhanced outcomes.

Identification of FIP1L1::PDGFRA rearrangements is important as they enable treatment with a tyrosine kinase inhibitor, which has significantly improved the overall prognosis for PDGFRA-rearranged neoplasms. Prospective studies assessing imatinib dosage, duration, and long-term safety are warranted in this cohort.

P3, N=117, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2024 --> May 2025