Tyrosine Kinase Inhibitors in the Treatment of Steroid Refractory Chronic Graft Versus Host Disease

Introduction:

Different novel drugs have been investigated for steroid-refractory chronic graft versus host disease (SR-cGVHD). Despite Rixulotinib approval, the need for more therapeutic options is still warranted. Tyrosine kinase (TK) inhibitors are known to inhibit pathways involved in cGVHD pathophysiology, including transforming growth factor (TGF)-β and platelet-derived growth factor receptor (PDGF-r) signaling pathways. Therefore, this drug class is currently under investigation in treating SR cGVHD.

Methods:

A comprehensive search was conducted across various data sets, including PubMed, Cochrane, and Embase. A review of the most recent data is summarized in this abstract.

Results:

Results from a randomized single-arm multicenter study highlighted the efficacy of Bruton's TK inhibitor ibrutinib with an acceptable safety profile. Similarly, multiple pilot studies show Imatinib, BCR/ABL TK inhibitor, as a suitable alternative treatment for steroid-refractory cGVHD. One study shows higher efficacy of Imatinib when combined with mycophenolate. A single phase I/II study highlighted the potential role of nilotinib. A list of complete and partial response rates of these studies with their most common adverse effects are listed in the table. 1.

A cumulative analysis of these studies showed that overall these three tyrosine kinase inhibitors showed a median complete response (CR) rate of 3.85% with ranges from 0 to 36.80% and a median partial response (PR) rate of 55.50% with ranges of 25-80%. These results, although not groundbreaking but still are encouraging.

Conclusion

Tyrosine kinase inhibitors are promising results in treating patients with SR cGVHD with a good side effect profile. More research is warranted to explore this drug class in this patient population.

No relevant conflicts of interest to declare.