Second-Line Therapy and Ruxolitinib for cGVHD

Segment 6 focuses on decision-making in second-line therapy for cGVHD, centering on the role of ruxolitinib. Dr. DeFilipp describes ruxolitinib as the most commonly used second-line agent, supported by randomized trial data demonstrating superior response rates and failure-free survival compared with best available therapy.

Ruxolitinib’s oral administration, broad organ activity, and favorable tolerability profile have contributed to widespread adoption. Ibrutinib is discussed as an alternative FDA-approved option, though its supporting trial was smaller and included a more selective patient population, raising questions about generalizability.

Using the case example, Dr. DeFilipp explains that early progression on steroids signals steroid-refractory disease and justifies prompt initiation of ruxolitinib while continuing steroids temporarily. The goal is to achieve disease control before tapering corticosteroids. The segment highlights the importance of anticipating treatment kinetics, recognizing that targeted agents require time to demonstrate benefit, and acting early to prevent irreversible organ damage.