Imatinib mesylate may induce long-term clinical response in FIP1L1-PDGFRα-negative hypereosinophilic syndrome

Abstract

The idiopathic hypereosinophilic syndrome (HES) comprises a heterogenous group of disorders characterized by marked blood eosinophilia with eosinophilia-associated organ damage. Eight patients with a median age at diagnosis of 42 years (range 19-67) received imatinib mesylate (IM) for FIP1L1-PDGFRα-negative HES resistant to previous conventional treatment. Median number of prior therapies was 3 (range 2-4). Median time from diagnosis to IM initiation was 112 months (range 2-293). Four patients were treated daily with 100 mg IM, whereas the remaining four patients were treated daily with 400 mg IM. Four male patients (50%) achieved complete haematologic response (CHR) after median of 7 days (range 3-150) using 100 mg daily IM (n = 2) and 400 mg (n = 2). Median duration of IM treatment for IM responders was 18 months (range 2-88). No adverse events were reported throughout the treatment duration. Two patients maintained CHR while on 100 mg weekly IM. Four patients (2 men and 2 women) failed IM treatment. Median duration of IM for non-responding patients was 3 weeks (range 3-12). Non-responding HES patients were significantly older and had lower percentage of blood eosinophilia when compared with IM responders. Our results suggest that IM, even at lower than conventional doses, may induce and maintain long-term remission for FIP1L1-PDGFRα-negative HES.

Successful Treatment For Chronic Eosinophilic Leukemia (CEL) With Imatinib Mesylate

“…There have been reports of patients with CEL NOS or Hypereosinophilic Syndrome who benefited from imatinib mesylate when given at doses higher than 400 mg per day [20]. In our patient, four months elapsed between the diagnosis and the start of treatment; complete hematologic response occurred in the second month of treatment with a dosage of 400 mg/day, In agreement with the results found in the literature when referring to similar cases [21].…”

Imatinib Treatment in PDGFRA‐Negative Childhood Hypereosinophilic Syndrome

“…It is unclear why certain patients without an identified mutation respond to imatinib. One study found that mutation‐negative responders tended to be younger with higher percentages of peripheral blood eosinophils compared to non‐responders, consistent with our patient's presentation and response . It may be that responders have other molecular aberrations not currently part of standard screening.…”

“…Corticosteroids remain the first line treatment but many suggest an imatinib trial for unresponsive or intolerant patients . Higher doses are often used and these patients often take longer to respond . It is unclear why certain patients without an identified mutation respond to imatinib.…”

Complete Response of Myeloid Sarcoma with <b><i>FIP1L1-PDGFRA</i></b>-Associated Myeloproliferative Neoplasms to Imatinib Mesylate Monotherapy

“…FIP1L1-PDGFRA -associated MPN is very responsive to IM, and durable remission can be achieved using IM and intensive chemotherapy despite disease evolution to AML or coexistence with T cell lymphoma in some affected patients [14,15]. In addition, many studies have shown that IM exhibits the same therapeutic potential in patients who present with chronic eosinophilic leukemia (CEL) or hypereosinophilic syndrome (HES) but without abnormalities in the PDGFRA, PDGFRB or FGFR1 gene [16,17,18]. …”