Abstract
Background: Tisagenlecleucel is a chimeric antigen receptor (CAR)-T cell therapy approved for the treatment of pediatric and young adult patients with B-cell acute lymphoblastic leukemia (B-ALL) that is refractory or in second or later relapse (r/r). Although tisagenlecleucel has proven efficacy and a manageable safety profile, pseudoprogression and eventual disease progression at extramedullary sites following tisagenlecleucel infusion have been reported. Depending on the site of extramedullary disease, inflammation around the extramedullary sites and/or progression may not be clinically tolerated in some patients.
Case Report: Herein we describe a 10-year-old female patient with r/r B-ALL following multiple lines of therapy. The patient was treated with tisagenlecleucel and subsequently developed pseudoprogression at extramedullary disease sites. Post infusion the patient experienced progressive swelling at extramedullary disease sites including intracranial, periorbital, scalp, retroperitoneal, intra-abdominal, and gingival lesions. A variety of anti-inflammatory agents were utilized to manage swelling, including tocilizumab, siltuximab, and corticosteroids. Although tocilizumab at first resulted in a rapid decrease in the size of visible subcutaneous scalp lesions, each subsequent dose was found to be progressively less effective, causing the patient to suffer due to the location and extent of enlarged extramedullary lesions. After continued growth of the lesions, biopsy revealed areas of necrotic inflammation as well as areas of continued leukemia involvement concerning for refractory disease. Ultimately, this patient died of complications of worsening leukemic progression at extramedullary sites.
Conclusion: Although tocilizumab is effective for the treatment of adverse events associated with CAR-T cell therapy, this case highlights unmet needs related to the identification and treatment of patients who will develop pseudoprogression, and potentially disease progression, at extramedullary sites post tisagenlecleucel infusion.