Optimal Treatment of Steroid-refractory Chronic Graft-versus-host Disease (cGvHD) in the Era of Novel drugs – a Systematic Review and Meta-analysis

Despite recent novel drug approvals and numerous treatment options, the steroid-refractory chronic graft-versus-host disease (SR-cGvHD) remains a significant clinical problem. We aimed to evaluate the efficacy and safety of available therapies in adult patients, based on a systematic review and meta-analysis. The analyzed treatment options included: axatilimab, belumosudil, extracorporeal photopheresis (ECP), ibrutinib, imatinib, rovadicitinib, and ruxolitinib. The endpoints included: best overall response rate (ORR), 12-month failure-free survival (FFS), the ratio of patients who discontinued therapy due to unacceptable toxicity, and the ratio of patients who experienced grade 3-5 adverse events. Rovadicitinib was the most effective treatment option, with manageable safety profile. Axatilimab produced a high response rate, yet worse 12-month FFS. It was a very safe option in SR-cGvHD. Despite promising efficacy, belumosudil produced the highest incidence of adverse events of all drugs. Ruxolitinib was proven to be an efficient and safe drug. Ibrutinib produced poor results in terms of both efficacy and safety. ECP was proven to be a very safe therapy, without spectacular efficacy. The analysis of imatinib yielded inconsistent results. As cGvHD is a disease with a heterogeneous clinical image, clinical experience remains an important factor that affects treatment choice for patients with certain disease manifestations.