New guidance on the management of pulmonary chronic graft versus host disease (cGvHD) following stem cell transplantation has been published to standardise a clinical approach for the first time.
Prevention and treatment of pulmonary cGVHD, which affects up to 14% of patients after allogeneic haematopoietic stem cell transplantation, are significant unmet needs and management of the condition remains a challenge, particularly as there are few therapeutic options available.
To drive advances in the care of patients, a joint European Respiratory Society (ERS) and European Society for Blood and Marrow Transplantation (EBMT) task force developed evidence-based recommendations for the treatment of bronchiolitis obliterans syndrome (BOS), given that it is the most common and best-described clinical phenotype of pulmonary cGvHD.
“These recommendations include important advancements that could be incorporated in the management of adults with pulmonary cGvHD, primarily aimed at improving and standardising treatment and improving outcomes,” the taskforce noted, in a paper published in the European Respiratory Journal (link here).
The taskforce, comprised of a range of experts including respiratory clinicians and haematologists, conditionally recommended inhaled corticosteroids with or without LABA in addition to a conventional immunosuppressive regimen.
They also backed the use of fluticasone, azithromycin and/or montelukast alongside immunosuppression, with the caveat that azithromycin be used with caution in patients with a high risk of secondary malignancies or those predisposed to cancer.
Use of imatinib was suggested, particularly as a potential option for patients with sicca symptoms and in those with chronic myeloid leukaemia, but experts noted that it was “a less favourable option” in those with cGvHD myalgia, gastrointestinal symptoms and anorexia.
In general, ibrutinib was not favoured as a treatment for adults with lung cGvHD phenotype BOS because of its toxicity profile in the overall cGvHD population, although the panel felt that it could possibly be a “valuable option” in some circumstances.
Extracorporeal photopheresis (ECP) was also conditionally recommended for progressive disease, and the experts also emphasised that lung transplantation is a potentially life-saving therapeutic intervention for patients with end-stage lung cGvHD phenotype BOS.
In ERS video interview, taskforce co-chair and respiratory consultant/lung transplant specialist Dr Saskia Bos, Translational Clinical Research, Newcastle University, said the guideline panel felt it important to stress that the decision on the type of treatment to proceed with should always be shared with the patient, “taking into account their preferences, the risk of side effects, and individual values”.
The panel also stressed that any treatment should be prescribed by physicians “who have the necessary expertise in their use and the possible side effects,” and that “interdisciplinary collaboration is of great importance to help this very specific patient population,” she said.
With regard to lung function testing and follow-up, the taskforce endorsed: spirometry at least every three months; full pulmonary function testing at diagnoses and annually thereafter, as well as at disease progression; and high-resolution chest CT scan at diagnosis or when there is respiratory decline.
They also suggested a package of wider healthcare interventions for adults with lung cGvHD phenotype BOS that included influenza immunisation and pneumococcal/COVID-19 vaccinations, long-term oxygen therapy when there is severe chronic resting hypoxaemia, and physical activity in patients with functional impairment, according to the paper.
While it is hoped that development of these evidence-based recommendations marks a significant step toward harmonising treatment approaches, the taskforce emphasised that all within the guideline are based on either low or very low certainty of evidence.
Also, limitations include the rarity of BOS-specific studies and their mostly retrospective nature, as well as heterogeneity across study protocols, treatment doses, conventional immunosuppression and lines of treatment, they said.
“One of the outcomes of this guideline should be to promote further research on the optimal treatment of patients with pulmonary cGvHD. Larger studies are urgently needed and should preferably be randomised in nature, specifically target BOS patients and use predefined similar endpoints,” they stressed.