Ruxolitinib-associated pulmonary alveolar proteinosis successfully managed by switching to belumosudil in chronic graft-versus-host disease.

Abstract

Secondary pulmonary alveolar proteinosis (PAP) is a rare but serious complication that can occur during immunosuppressive therapy for chronic graft-versus-host disease (GVHD). It is characterized by the intra-alveolar accumulation of surfactant due to drug-induced alveolar macrophage dysfunction. Managing PAP while maintaining control of active chronic GVHD represents a significant clinical challenge, particularly with regard to the optimal strategy for transitioning between immunosuppressive agents. A 25-year-old male with severe chronic GVHD developed a dry cough and bilateral ground-glass opacities (GGOs) after 2.8 years of ruxolitinib treatment. A lung biopsy confirmed secondary PAP. Ruxolitinib was tapered and replaced with belumosudil. Following the switch, the GGOs resolved rapidly within one month, and chronic GVHD remained stable, eventually allowing for successful corticosteroid tapering. Unlike ruxolitinib, belumosudil is thought to preserve the signaling pathways essential for alveolar macrophage activation. Transitioning to belumosudil may therefore represent a promising therapeutic strategy for managing secondary PAP in patients with chronic GVHD who require ongoing immunosuppressive therapy.