Biologic therapies for hypereosinophilic disorders: From tyrosine kinase inhibitors to monoclonal antibodies. Towards an increasingly customized management?

Iurlo, Alessandra; Cattaneo, Daniele

doi:10.1016/j.blre.2022.101014

Cited by 4 publications

(2 citation statements)

References 103 publications

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“…Currently, imatinib is the drug of choice for myeloid neoplasms with eosinophilia and PDGFRA/B rearrangement, as its hematologic benefit has been confirmed in several studies, even at lower dosages than those used for chronicmyeloidleukemia. 3 Here we describe the case of two 33-year-old Caucasian men who presented with both these conditions, achieving complete response on imatinib.…”

Section: Introductionmentioning

confidence: 96%

“…Recurrent genetic abnormalities ( PDGFRA/B , FGFR1 ) have a low incidence among eosinophilic disorders and, in particular, FIP1L1::PDGFRA fusion gene median frequency has been reported to be approximately 23% (range 3%–56%). Currently, imatinib is the drug of choice for myeloid neoplasms with eosinophilia and PDGFRA/B rearrangement, as its hematologic benefit has been confirmed in several studies, even at lower dosages than those used for chronic myeloid leukemia 3 …”

Section: Introductionmentioning

confidence: 99%

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Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases

Bellani

Croci

Bucelli

et al. 2023

The Journal of Dermatology

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Lymphomatoid papulosis (LyP) is a benign condition, listed among primary cutaneous CD30+ lymphoproliferative disorders. Its typical picture consists of relapsing–remitting papular lesions and it can be encountered in the course of a hematologic disease, at times representing its first manifestation. Hypereosinophilic syndromes are a heterogeneous group of disorders characterized by persistent peripheral blood hypereosinophilia that may lead to life‐threatening organ damage. Among eosinophilic disorders, the subtype identified as myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene fusions has aroused particular interest due to its excellent response to tyrosine kinase inhibitors, including imatinib. Here, we described the case of two 33‐year‐old men presenting with LyP and myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement who achieved complete clinical and molecular remission of both conditions a few months after starting imatinib.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases

Bellani

Croci

Bucelli

et al. 2023

The Journal of Dermatology

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Value and limitations of targeted next-generation sequencing in idiopathic hypereosinophilia: an integrative diagnostic tool in challenging cases

Cattaneo,

Marchetti,

Bucelli

et al. 2024

Clin Exp Med

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Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 28 consecutive patients admitted to our hospital between September 2011 and November 2021 for idiopathic hypereosinophilia (HE).Bone marrow (BM) morphology was evaluated in 22 patients: while in six subjects BM was unremarkable, in the remaining cases an increase in BM eosinophils was observed, together with a slight increase in BM fibrosis (MF-1) in 5/22 patients.A total of 4/28 patients had at least one genetic lesion by targeted NGS. In particular, the genes involved were: two each of TET2 and DNMT3A; and one each of JAK2V617F, ASXL1, PPM1D, and ZBTB33. Notably, JAK2V617F and TET2 mutations co-occurred, with the JAK2V617F-mutated sample also carrying TET2 lesions. Median VAF was 21%, with the exception of the oncodriver JAK2V617F, which showed a VAF > 50% in the reported case. Of note, of the four cases bearing lesions, 2/4 had multiple hits in different genes.While in recent years mutational analysis using NGS has proven to be able to differentiate clonal hematopoietic neoplasms from reactive processes in diagnostically difficult cases, we found somatic mutations in only 14.3% of patients who acceded to our hospital for idiopathic HE. More importantly, excluding the JAK2V617F-mutated case with an underlying MPN-Eo diagnosis, NGS was able to identify somatic mutations in only three cases, all older than 70 years. Consequently, the detection of these mutations in idiopathic HE patients should be interpreted with caution and only in the context of other supportive clinical-pathological findings.

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Phase II trial of imatinib mesylate in patients with PDGFRA/B‐negative hypereosinophilic syndrome

Kim,

Park

et al. 2024

Br J Haematol

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SummaryThe role of imatinib in PDGFRA/B‐negative hypereosinophilic syndromes (HES) is controversial because of the heterogeneity of HES and the scarcity of prospective studies. We conducted a phase II clinical trial to evaluate the efficacy of imatinib in PDGFRA/B‐negative HES. Thirty‐two patients were treated with imatinib (100–400 mg daily), and the molecular basis of their response was identified using whole‐exome sequencing (WES) and whole‐transcriptome sequencing (WTS). The haematological response rate was 46.9%, with a complete haematological response (CHR) rate of 18.8%. The median time to response was 1.5 months. Among the six patients who achieved CHR, five maintained it until the 24th cycle of imatinib and one lost response after 20 months. The median progression‐free survival was 4.3 months. WES and WTS were conducted for 11 patients. The number of non‐silent mutations did not differ between responders and non‐responders. Nine differentially expressed genes, including SNORD15A, were downregulated in responders. STAT5B::RARA, PAK2::PIGX, and FIP1L1::CHIC2 fusions were identified in patients with sustained responses, and RNF130::BRAF and WNK1::KDM5A fusions were identified in non‐responders. Imatinib, along with an appropriate biomarker, could be a promising option for PDGFRA/B‐negative HES.

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Biologic therapies for hypereosinophilic disorders: From tyrosine kinase inhibitors to monoclonal antibodies. Towards an increasingly customized management?

Cited by 4 publications

References 103 publications

Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases

Lymphomatoid papulosis associated with myeloid neoplasm with eosinophilia and FIP1L1::PDGFRA rearrangement: Successful imatinib treatment in two cases

Value and limitations of targeted next-generation sequencing in idiopathic hypereosinophilia: an integrative diagnostic tool in challenging cases

Phase II trial of imatinib mesylate in patients with PDGFRA/B‐negative hypereosinophilic syndrome

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