Long-term effects of ruxolitinib versus best available therapy on bone marrow fibrosis in patients with myelofibrosis

Abstract

BackgroundMyelofibrosis (MF) is a life-shortening complication of myeloproliferative neoplasms associated with ineffective hematopoiesis, splenomegaly, and progressive bone marrow (BM) fibrosis. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib has been shown to improve splenomegaly, symptom burden, and overall survival in patients with intermediate-2 or high-risk MF compared with placebo or best available therapy (BAT).MethodsThe effects of ruxolitinib therapy for up to 66 months on BM morphology in 68 patients with advanced MF with variable BM fibrosis grade were compared with those in 192 matching patients treated with BAT. Available trephine biopsies underwent independent, blinded review by three hematopathologists for consensus-based adjudication of grades for reticulin fibrosis, collagen deposition, and osteosclerosis.ResultsRuxolitinib treatment versus BAT was associated with greater odds of BM fibrosis improvement or stabilization and decreased odds of BM fibrosis worsening based on changes from baseline in reticulin fibrosis grade. Generally, these changes were accompanied by a sustained higher level of individual spleen size reduction and regression of leukoerythroblastosis. Patients with more advanced baseline fibrosis showed lower spleen size response.ConclusionsThe finding that long-term ruxolitinib therapy may reverse or markedly delay BM fibrosis progression in advanced MF suggests that sustained JAK inhibition may be disease-modifying.Trial registrationINCB18424-251, ClinicalTrials.gov identifier NCT00509899.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0585-5) contains supplementary material, which is available to authorized users.

The Myeloproliferative Neoplasm Landscape: A Patient’s Eye View

“…In clinical trials, ruxolitinib was shown to significantly reduce spleen size, ameliorate debilitating MF-related symptoms, and improve QoL in patients with intermediate-2 or high-risk MF versus best available treatment, with overall survival also improved versus placebo [38,39]. The benefits of ruxolitinib on spleen size and overall survival have been shown to be maintained over longer-term therapy [40,41], and sustained treatment was also associated with greater odds of bone marrow fibrosis improvement or stabilization and decreased odds of bone marrow fibrosis worsening in a large proportion of patients with MF versus best available treatment [42]. Additionally, ruxolitinib has demonstrated significant reductions in spleen size, control of haematocrit, and improvement of PV-related symptoms.…”

Osteolytic Lesions in Primary Myelofibrosis and Effect of Ruxolitinib Therapy: Report of a Case and Literature Review

“…In addition, a possible effect of ruxolitinib on bone marrow fibrosis has been reported in both clinical studies [14] and in real-life experience [15-17]. …”

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

“…BCR-ABL tyrosine kinase inhibitors (TKI) have fundamentally changed the therapeutic paradigm of chronic myeloid leukemia (CML) and possibly of ALL with BCR-ABL mutations in the near future [22,23]. JAK2 inhibitors, ruxolitinib and fedratinib, are major therapy options for myelofibrosis [24][25][26]. Inhibitors for BCL-2, venetoclax, and Bruton tyrosine kinase, ibrutinib and acalabrutinib, are playing major roles in therapy for chronic lymphoid leukemia as well as in mantle cell lymphoma [27][28][29][30].…”