P1382: RUXOLITINIB USE IN A REAL WORLD ACUTE AND CHRONIC GRAFT VERSUS HOST DISEASE COHORT IN THE NETHERLANDS: A RETROSPECTIVE STUDY

Abstract

Background: Preclinical data showed that Janus Kinase (JAK) signaling plays an important role in the pathogenesis of Graft versus Host Disease (GVHD) and several clinical studies showed remarkable clinical efficacy in both acute and/or chronic steroid-refractory (SR)-GVHD patients. However, these clinical results have not yet been repeated in real world cohorts with long term follow-up. Furthermore, infectious complications have not been highlighted in published clinical trials whilst these remain a significant problem in daily practice. Aims: To assess the response of acute and/or chronic SR-GVHD patients to ruxolitinib treatment and to assess side-effects of ruxolitinib treatment occurring in adult acute and/or chronic SR-GVHD patients. Methods: We performed a retrospective analysis of 121 consecutive patients treated with ruxolitinib for either acute or chronic GVHD. Patients were included from 3 academic centers in the Netherlands from 2014 to 2019. Patients provided written informed consent, with the exception of deceased patients in accordance with the local ethics committee. Patient data were extracted by personnel from an independent CRO to minimize reviewer bias. Patient data were anonymized. Results: 121 patients were included in the study of whom 54 were diagnosed with acute and 67 patients with chronic GVHD. Selected baseline characteristics are depicted in Table 1. The overall response rate at day 28 of acute GVHD was 70% (38/54) with a complete response in 50% of patients (27/54). At timepoint 6 months after initiation of ruxolitinib for chronic GVHD, the majority of patients showed stable disease. The overall response rate at 6 months in chronic GVHD was 28% (19/67) with a complete response in 13% of patients (9/67). Ruxolitinib use was mainly complicated by infections and hematological toxicity. Of the reported (S)AE’s possibly related to ruxolitinib, 38% were infectious and 13% were hematological. Severity of infections ranged from grade 1 to grade 5, median grade 2. Most infections were viral (43%), followed by bacterial (19%) and fungal or mould infections (14%). During follow up mortality was 14,9% (18 patients) of which 6 cases were due to uncontrolled GVHD, 5 cases due to infections and 3 patients died of relapse of their primary malignancy, 4 patients died of other causes. Image:Summary/Conclusion: In a real world cohort of GVHD patients treated with ruxolitinib we observed in patients with acute GVHD a complete response rate at day 28 of 50%. Overall response rate at 6 months in cGVHD patients was 28%. Infectious adverse events were common in both acute and chronic GVHD patients and were mainly caused by viral pathogens.