Therapeutic response of metastatic angiomatoid fibrous histiocytoma carrying EWSR1‐CREB1 fusion to the interleukin‐6 receptor antibody tocilizumab

Abstract

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that has been associated with EWSR1-CREB1 gene fusion. Outcome in patients with unresectable distant metastases is generally fatal. Interleukin-6 (IL-6) secretion has been described in tumors with EWSR1-CREB1 fusion, and may promote tumor growth due to autocrine stimulation. Tocilizumab is an IL-6 receptor antibody that has potential benefit as a targeted therapy in refractory neoplasms with IL-6 secretion. We describe a child with metastatic AFH with EWSR1-CREB1 fusion and elevated IL-6 whose disease progressed during treatment with traditional chemotherapeutic agents, but improved after targeted therapy with tocilizumab.

An integrative histopathological and epigenetic characterization of primary intracranial mesenchymal tumors, FET:CREB‐fused broadening the spectrum of tumor entities in comparison with their soft tissue counterparts

“…Although most cases grouped together and the existence of a distinct methylation class could potentially be masked by the low number of cases included, the remaining tumor samples did segregate into different groups. First, one of our cases shared clinical (young age), radiological (presence of a cystic component) ( 57 ), histopathological (presence of the triad), and molecular ( EWSR1:ATF1 fusion, the preferential fusion transcripts in AFH of the soft tissue ( 2 , 3 , 4 , 5 , 7 , 8 , 12 , 13 , 15 , 16 , 17 , 18 , 58 , 59 , 60 , 61 , 62 , 63 , 64 )) features with AFH of the soft tissue but no other tumor location was found. Further samples with DNA‐methylation analyses are needed to confirm that true primary AFH exist in the CNS.…”

Tocilizumab for the treatment of paraneoplastic inflammatory syndrome associated with angiomatoid fibrous histiocytoma

“…A partial metabolic response and remission of IL6-induced PIS with tocilizumab was previously reported in a case of a paediatric metastatic AFH with an EWS-CREB1 fusion. 5 Treatment with tocilizumab led to remission of severe IL6-induced PIS associated with metastatic AFH, where IL6 overproduction is likely related to the oncogenic fusion involving transcription factors regulating IL6. The contribution of this anti-IL6 antibody to clinical tumour growth factor in AFH remains to be established, and will be further explored.…”

Angiomatoid Fibrous Histiocytoma With ALK Expression in an Unusual Location and Age Group

“…Peak incidence lies within the first three decades, however they can occur at any age. Patients with tumours harbouring the EWSR1-CREB1 fusion may present with fever, malaise and anemia as part of a paraneoplastic syndrome secondary to CREB-mediated interleukin 6 upregulation [7].…”

“…Adjuvant chemotherapy and or radiotherapy is indicated for unresectable lesions and metastatic disease. Case reports describing the efficacy of targeted therapeutics against IL-6 have also been published in the literature [7]. The majority of AFHs follow a benign course, however case series have demonstrated up to 15% local recurrence risk [4,26].…”