Bleomycin-induced Pneumonitis in a Child Treated With Nintedanib: Report of the First Case in a Childhood

Abstract

Pulmonary fibrosis caused by bleomycin-induced pneumonia (BIP) is the most important side effect limiting the use of bleomycin and is mainly treated with corticosteroids. However, 1% to 4% of patients do not respond to corticosteroid therapy. Idiopathic pulmonary fibrosis and BIP develop by similar pathophysiological mechanisms. Nintedanib is a tyrosine kinase inhibitor used successfully in the treatment of idiopathic pulmonary fibrosis and there is no information about its use in BIP treatment. Here, we would like to present a 13-year-old boy with Hodgkin lymphoma who developed BIP after 2 cycles of ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) and 4 cycles of BAECOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), whose respiratory failure impaired despite corticosteroid therapy, but was successfully treated with nintedanib.

Fibrotic lung diseases in children

“…The first case about the use of nintedanib in bleomycin‐induced pneumonia (BIP) was reported by Gundogan et al A 13‐year‐old boy with Hodgkin lymphoma who developed BIP with respiratory failure despite corticosteroid therapy after chemotherapeutic agents including bleomycin was presented. The patient was successfully treated with nintedanib 44 . The dose of nintedanib administered in this case was 200 mg/day.…”

“…26 In this study eligible children and with nintedanib. 44 The dose of nintedanib administered in this case was 200 mg/day. In a similar case of ours, nintedanib given as BIP treatment failed in an 11-year-old child whose respiratory functions were so poor that he could not perform PFT.…”

“…47 Although the efficacy of using antifibrotic agents in children is mostly supported by case reports, antifibrotic treatments can also be given a chance in case of progressive PF after other treatments have been failed. 44,46,48,49 Nevertheless, it is evident that additional comprehensive research is required to ensure the safe utilization of antifibrotic therapies and these treatments should be used with caution. A treatment strategy algorithm in light of available data is illustrated in Figure 7.…”

“…Patients who meet at least one of the following criteria despite appropriate clinical management within the preceding 24 months were accepted as having progressive PF: relative decline in FVC ≥ 10% predicted; relative decline in FVC ≥ 5 to <10% predicted and worsening of respiratory symptoms; relative decline in FVC ≥ 5 to <10% predicted and increased extent of fibrosis on HRCT; worsening of respiratory symptoms and increased extent of fibrosis on HRCT 47 . Although the efficacy of using antifibrotic agents in children is mostly supported by case reports, antifibrotic treatments can also be given a chance in case of progressive PF after other treatments have been failed 44,46,48,49 . Nevertheless, it is evident that additional comprehensive research is required to ensure the safe utilization of antifibrotic therapies and these treatments should be used with caution.…”

Effectiveness and safety of nintedanib in prevention of pulmonary fibrosis induced by bleomycin in malignant ovarian germ cell tumour: study protocol for a randomised, double-blind, placebo-controlled trial

“…Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF) in many countries, and several clinical trials have proven its effectiveness and safety in the treatment of IPF 16 17. Recently, Gundogan et al also reported a 13-year-old lymphoma patient treated with a bleomycin-containing chemotherapy regimen who developed bleomycin-induced pneumonia that was successfully treated with nintedanib 18. Moreover, nintedanib also showed antitumour effects in some reports 19 20…”