The use of dupilumab in bronchiolitis obliterans after hematopoietic stem cell transplant.

BACKGROUND

Bronchiolitis obliterans is a serious pulmonary manifestation of chronic graft-versus-host disease (cGVHD) following hematopoietic stem cell transplant (HSCT). Bronchiolitis obliterans is typically treated with a combination of inhaled steroids, azithromycin, montelukast and immunosuppressants. There are no curative treatments other than lung transplant, however, and additional therapies remain an unmet need.

CASE PRESENTATION: Here we report two patients who developed bronchiolitis obliterans following HSCT. Both developed strong type 2 inflammatory markers including high eosinophil counts ≥ 1000 cells/mm3 and had history that was concerning for a possible concomitant asthma. Patient 1 had worsening symptoms after exposure to old wood during a construction project, and patient 2 had a history of asthma. Both patients were started on the anti-IL4 receptor monoclonal antibody, dupilumab, to target this type 2 inflammation. Both patients reported some symptomatic improvement but only had limited changes in their spirometry. Their courses were further complicated by multiple respiratory infections in the setting of immunosuppression for cGVHD.

CONCLUSION

These cases highlight the unmet need for treatment in the bronchiolitis obliterans space and the potential role of type 2 inflammation in their pathogenesis. Given the complex nature of these cases and the infectious risks of immunosuppression, larger studies would be needed to better assess the potential role of dupilumab in this population.