Diffuse alveolar hemorrhage with pseudoprogression during nivolumab therapy in a patient with malignant melanoma

Abstract

Nivolumab, an anti-PD-1 antibody, has been shown to be effective in many cancers, such as malignant melanoma and lung cancer; however, nivolumab therapy can result in pseudoprogression. Diffuse alveolar hemorrhage (DAH) is persistent or recurrent pulmonary hemorrhage as a result of drugs, autoimmune diseases, or infections. DAH with pseudoprogression during nivolumab administration has rarely been reported. Herein, we describe our experience with one such case. A 41-year-old woman exhibited bloody sputum and ground glass opacities in the lungs along with tumor growth during nivolumab therapy for multiple lung metastases of malignant melanoma. We diagnosed DAH with pseudoprogression as a result of nivolumab and administered steroid therapy. The DAH subsequently improved and the tumor shrank. This case illustrates that nivolumab can cause DAH with pseudoprogression, which can be controlled by steroid therapy. Thus, if bloody sputum and ground glass opacities in the lungs are observed with tumor growth during nivolumab administration, steroid therapy should be considered to control DAH with pseudoprogression.

Keywords: Diffuse alveolar hemorrhage; immuno-checkpoint inhibitor; lung metastasis; nivolumab; pseudoprogression.

Figure 1

(a) Chest computed tomography showing multiple lung metastases before nivolumab therapy. (b,c) A slight increase in the size of the lung metastatic lesions and the appearance of nearby ground glass opacities (GGOs) (triangle) are observed after one and two months of therapy. A slight increase in the size of lung metastatic lesions without GGOs is also observed (blue arrows) (d) There are multiple lung metastases and increased GGOs (triangles), as well as the emergence of new GGOs in areas without lung metastases (red arrows). (e) Disappearance of GGOs and reduction of multiple lung metastases after steroid therapy.

Figure 2

Bronchoalveolar lavage fluid showed a progressively bloody return from the right upper lobe.