Assessment and Early Management After Steroid Failure in Chronic GVHD

Assessment and Early Management After Steroid Failure in Chronic GVHD

This segment discusses the evolution in chronic graft-vs-host disease (GVHD) treatment paradigms over the past 2 decades. The speaker reflects on how training 20 years ago emphasized patience with steroid therapy—starting high-dose prednisone and waiting months to assess response before considering alternatives. In 2025, this approach has fundamentally changed due to the availability of multiple effective second-line agents. The current philosophy involves having a “short leash” for steroids, typically moving to second-line therapy within 2 to 3 weeks rather than waiting for true steroid-refractory disease. The primary motivations for adding second-line agents are now the need to discontinue steroids or inadequate quality of life improvement, rather than complete treatment failure.

Response assessment in busy clinical practice requires practical modifications of the comprehensive National Institutes of Health criteria, which score all 8 cardinal organs but are time-prohibitive when seeing 20 to 25 patients daily. The recommended approach focuses on dominant organ involvement, particularly calculating lung scores and FEV1 for pulmonary disease or assessing body surface area involvement and sclerotic changes for skin manifestations. A systematic head-to-toe assessment covering dry eyes, mouth symptoms, joint range of motion, and gastrointestinal symptoms remains important. Electronic medical record systems with built-in flow sheets and dropdown menus facilitate documentation and longitudinal comparison of responses over time.

Patient-reported outcomes (PROs) have become essential in both clinical practice and research for chronic GVHD assessment. The heterogeneous nature of the disease means that partial responses can be either transformational or minimally impactful for individual patients. Quality of life conversations with patients are crucial for determining treatment success, as the same degree of organ improvement may have vastly different impacts on different patients' daily functioning and expectations. This patient-centered approach has led to PROs becoming mandatory components of current chronic GVHD clinical trials, recognizing that objective organ response may not correlate with meaningful clinical benefit for patients.