(P 254) EOSINOPHILIC FASCIITIS (EF) AS A COMPLICATION OF NATURAL KILLER (NK) CELL-BASED IMMUNOTHERAPY IN A YOUNG ADULT WITH RECURRENT METASTATIC EWING SARCOMA

Objective: EF is a rare inflammatory connective tissue disease characterized by painful edema, erythema, thickening of muscle fascia and surrounding tissues, and sclerosis with limited range of motion [1]. Definitive diagnosis is an ongoing area of study but is supported by key findings on physical exam, imaging, and histopathology [2]. While its etiology remains unknown it is frequently associated with immunomodulation and malignancy

Methods: n/a

Results: A 19 year-old male with metastatic Ewing Sarcoma of the right tibia presented with recurrence to the primary site and right humerus, a year off standard of care therapy per COG AEWS1221 protocol. He underwent four cycles of salvage Irinotecan/Temozolomide but discontinued due to intolerable side effects. He then enrolled in a trial investigating universal donor, TGF-B imprinted NK cell infusions with dual chemotherapy for recurrent sarcoma (NCT05634369). Initial infusions were well-tolerated, however during Cycle 4 he reported painful bilateral leg pitting edema, weight gain and orthopnea refractory to oral diuretics. By Cycle 10, symptoms had progressed with a skin-tightening sensation, limited knee flexion, and foot drop of the right leg, and induration of both legs with linear depressions following venous tracks (‘Groove sign’). He was referred to Dermatology where punch biopsy showed marked dermal fibrosis, patchy lymphocytic infiltrate, sclerotic collagen, and thick/hyalinized fibrous bands in subcutaneous tissue; combined exam and pathology findings all consistent with EF. Oral methylprednisolone was prescribed but declined due to the side effect profile. He continued to have stable disease on treatment but was unfortunately taken off study due to a Grade 3 anaphylactic event during NK cell infusion. Since being off treatment the patient’s edema, discoloration and limb function have gradually improved without other interventions.

Conclusion: EF remains an uncommon but known adverse event reported with the use of immunomodulating agents. Most cases were described in patients receiving checkpoint inhibitors, especially PD-1 inhibitors such as nivolumab and pembrolizumab (3,4); to our knowledge, this is the first reported case of EF as a complication of NK cell adoptive immunotherapy for Ewing Sarcoma. With the rising trend of using established and novel immunomodulators in the treatment of various cancers (5), clinicians should remain vigilant in monitoring for complications of these therapies including atypical conditions like EF.