Pulmonary manifestations of chronic graft-versus-host disease (cGVHD) include bronchiolitis obliterans syndrome (BOS), which severely impacts patient quality of life and lung function. Targeted agents are increasingly being used as treatment, offering the potential for more effective management of pulmonary cGVHD.

When talking about pulmonary cGVHD, most of the time, we are referring to BOS. One problem with pulmonary manifestations of cGVHD such as BOS is that patients can be asymptomatic early in the disease course, and, when they do present with symptoms, the disease is more advanced and often more difficult to treat.

Recent guidelines recommend performing pulmonary function tests at more frequent intervals following transplant to better catch changes in lung function. I agree with this recommendation in principle, but I also acknowledge that the logistics of scheduling with an increasing number of transplant recipients can prove to be difficult. However, we can use spirometers in the clinic to get quick initial assessments and then, if there is a signal of impaired function, send that patient for a more comprehensive assessment.

If a patient with cGVHD develops BOS, my first choice for treatment is systemic therapy in addition to fluticasone, azithromycin, and montelukast (the FAM regimen), as well as a beta agonist. We typically do not use high doses of steroids in these patients because they can cause a lot of toxicities. Ruxolitinib is one of the most used therapies for overall cGVHD, but data from the REACH3 trial suggested that lung responses were not great. We recently published results from a nonrandomized, phase 2, multicenter, clinical trial of ruxolitinib in patients with BOS. The best lung-specific overall response rate over the first year of treatment was more encouraging at approximately 34%.

Similarly, a combined analysis of data from 2 clinical trials of belumosudil reported a best overall response rate for pulmonary cGVHD of 32%. One thing we have seen with ruxolitinib and belumosudil is that patients with mild or moderate disease seem to respond better than those with severe disease. That also emphasizes the take-home point that early detection and treatment may lead to better responses.

Recently, axatilimab, a CSF-1 receptor–blocking monoclonal antibody, was US Food and Drug Administration (FDA) approved for the treatment of cGVHD that has failed 2 or more lines of systemic therapy. Data on axatilimab from the AGAVE-201 study look encouraging in patients who had sclerotic disease in the skin and those with lung manifestations. I think that the field is currently focused on how we can optimize the use of these newer FDA-approved targeted agents in clinical practice and learn in more detail how they work and how well they do or do not work in pulmonary cGVHD so that we can come up with better strategies to help these patients.