Response: Imatinib in lung cGVHD of mild to moderate severity

We appreciated the letter written by Stadler and colleagues reporting their experience with imatinib for treating patients with severe chronic graft-versus-host disease (GVHD) involving lungs. They had results that were less satisfactory than ours, only 2 of their 9 patients benefiting from partial response (PR). We treated with imatinib 19 patients with cGVHD, 11 of them with lung involvement; the study approval was obtained from the institutional review board of Potenza (Italy). Informed consent was provided according to the Declaration of Helsinki. Clearly, our experience was more encouraging, as 6 of our 11 patients markedly improved (reduction by 2 or more points) their lung function score (LFS), and 2 of them were able to discontinue steroid therapy.¹  As also suggested by Stadler et al, several factors may easily explain this apparent discrepancy of efficacy. Indeed, in the 9 patients treated by Stadler and colleagues, lung deterioration was much more severe, as shown by the values of forced expiratory volume (FEV₁). It is reasonable to conceive that when lung tissue damage is too severe, even an antifibrotic effect^2,3  will not be able to restore respiratory function. Support for this interpretation is provided by the observation that also our 2 patients with the worst lung deterioration (namely, those with LFS ≥ 5) did not respond to treatment. Moreover, patients treated by Stadler et al were older than ours, and it is possible that young patients have a better capacity to repair tissue damage. Finally, we found that most patients converted from no response to PR or from PR to complete response in 3 to 6 months of treatment, suggesting that the prolongation of treatment can increase both the response rate and the quality of response at lung level. Six of the 9 patients treated by Stadler et al were given imatinib mesylate for only 1 to 4 months, which possibly contributed to the unsatisfactory results they reported. In view of all these findings, we confirm our recommendation that, in the absence of an early response (ie, within 1-3 months), imatinib should not be discontinued before reaching at least 6 months of treatment. Earlier discontinuation may be premature or even detrimental.

In conclusion, available evidence suggests that imatinib mesylate may be effective in a relevant proportion of patients with lung involvement by chronic GVHD, especially in those with mild to moderate deterioration of pulmonary function and if treatment is prolonged over time. Whether other tyrosine kinase inhibitors, such as nilotinib and dasatinib, may lead to even better results in the treatment of chronic GVHD with fibrotic features remains to be proved with proper future studies.