Measuring Therapeutic Response in Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. Response Criteria Working Group Report

Abstract

The lack of standardized criteria for quantitative measurement of therapeutic response in clinical trials poses a major obstacle for the development of new agents in chronic graft-versus-host disease (GVHD). This consensus document was developed to address several objectives for response criteria to be used in chronic GVHD-related clinical trials. The proposed measures should be practical for use both by transplantation and nontransplantation medical providers, adaptable for use in adults and in children, and focused on the most important chronic GVHD manifestations. The measures should also give preference to quantitative, rather than semiquantitative, measures; capture information regarding signs, symptoms, and function separately from each other; and use validated scales whenever possible to demonstrate improved patient outcomes and meet requirements for regulatory approval of novel agents. Based on these criteria, we propose a set of measures to be considered for use in clinical trials, and forms for data collection are provided (). Measures should be made at 3-month intervals and whenever major changes are made in treatment. Provisional definitions of complete response, partial response, and progression are proposed for each organ and for overall outcomes. The proposed response criteria are based on current expert consensus opinion and are intended to improve consistency in the conduct and reporting of chronic GVHD trials, but their use remains to be demonstrated in practice.

Impact of extracorporeal photopheresis on skin scores and quality of life in patients with steroid-refractory chronic GVHD

“…11 The extent of cutaneous involvement was measured by the percentage of body surface area involved. This measurement was subdivided to include the percentage of erythema and the percentage of movable and non-movable sclerosis.…”

“…11 Response was primarily assessed by one dermatologist to avoid inter-observer variation. A complete overall response was defined as a complete resolution of all symptoms and signs of cGVHD.…”

“…1 A change of 6-7 points in cGVHD SS was considered to be a clinically significant change. 11,12 The second was the dermatology QoL index (DLQI). 13 A change of 3.2 points in the DLQI score was considered clinically significant.…”

Phase-1/-2 study of pomalidomide in chronic GvHD

“…cGvHD activity was assessed at baseline, every 3 cycles and when therapy was stopped for any reason, using the NIH Criteria. 12,13 Complete organ response (CR) was defined as resolution of all reversible cGvHD features in a specific organ, partial organ response (PR) as ⩾ 50% improvement in the specific organ, progression as ⩾ 25% increase on the same scale and stable disease as no change in cGvHD. Complete overall response was defined as complete resolution of all reversible features in all affected organs and partial overall response as an improvement in at least one organ without progression in any other affected organ.…”

Graft-Versus-Host Disease (GvHD)

“…The global scoring system of NIH 2014 was developed to be suitable for clinical trial assessments and reflects the clinical impact of cGvHD on the patient's functional status and organ impairment and is defined by Jagasia et al 2015 as (Table 11.1): Pavletic et al (2006) proposed a set of measures for assessing the response to treatment of cGvHD patients. These should be performed at 3 monthly intervals or whenever a major change occurs.…”