Pediatric Blood & Cancer | 2021
Single‐agent rituximab for treatment of multifocal and multiple relapsed pulmonary inflammatory myofibroblastic tumor in an adolescent patient
Abstract
Dear Editor: Inflammatory myofibroblastic tumors (IMTs) are predominantly pediatric mesenchymal, nonmalignant, locally invasive masses. They are characterized by spindle cell component with infiltration by mononuclear inflammatory cells.1 Genetic aberrations can be present, most commonly rearrangements of anaplastic lymphoma kinase (ALK).1 Treatment is difficult due to frequent recurrence and metastasize.2,3 Surgical resection is the main stay of therapy when feasible.4–6 When a complete excision is not feasible, therapies indicated include pathway-directed therapies,7–10 nonsteroidal anti-inflammatories with steroids, chemotherapy, and/or radiation to variable effect.11,12 Rituximab, an anti CD20monoclonal antibody, has been used successfully in two previous cases.13,14 We care for an 18-year-old female patient who was initially treated for intermediate risk Hodgkin lymphoma with chemotherapy and radiotherapy leading to complete response. Cancer predisposition evaluation found one variant of unknown significance in gene NBN. Threemonths off therapy, surveillance scans showedmultiple new pulmonarymasses. Biopsy revealed inflammatorymyofibroblastic tumors. Immunohistochemical stainswere negative for ALK protein.Molecular cytogenetics were attempted but unsuccessful. Initial treatment with two courses of oral prednisone (6 mg/m2/dose) lead to near complete resolution initially but with rapid recurrence. Second recurrence was treated with weekly vinblastine (4 mg/m2/dose) and oral methotrexate (20 mg/m2/dose) plus celecoxib daily (200 mg) for four cycles with improved but persistent disease. Dexamethasone was added and vinblastine was discontinued for two additional cycles. Ten months on treatment scans demonstrated multiple recurrent masses. For fifthline treatment, due to the potential for false negative ALK detection by ICH, an empiric trial of ALK-inhibitor crizotinib (400 mg) was tried for 6 months but discontinued due to disease progression. Repeat biopsy and review re-demonstrated IMT, this time with programmed death ligand 1+ (PDL1+) mutation; sixth-line pembrolizumab (200 mg once every 3weeks) was initiated. Thiswas discontinued after 3months due to disease progression. Seventh-line rituximab 375 mg/m2/dose every other week for four total doses was given. She was treated with supportive measures for symptomatic joint pain. Treatment course had no grade three or four toxicities. Follow-up imaging at end of monotherapy with rituximab showed complete resolution. This casehighlights successful treatment for amultifocal andheavily pre-treated inflammatory myofibroblastic tumor. Specific to this case, first-line treatment, surgical resection, was not feasible. While ALK rearranged tumors demonstrate response to targeted therapies,15,16 tumorswithoutALK rearrangements require additional targeted treatments. Rituximab is hypothesized to be effective in this lymphocytemediated process. Rituximab was well tolerated and there were no grade three or four toxicities, consistentwith previously described toxicity profile. There is a recognized risk of b-cell aplasia and immune suppression with rituximab. Long-term remission has been robust: 19 months without relapse by imaging, 25 months since treatment without suggestion of relapse by symptoms. Rituximab should be considered as an option for treatment in patients with IMTs, especially when surgical resection may not be a feasible treatment option, such as multifocal tumors. Further studies are needed to investigate the broader clinical efficacy of rituximab in this patient population in the future.