iMTSS: A two-axis, prognostic framework for post-transplant myelofibrosis

Results from an international, retrospective study evaluating an integrated framework to quantify post-transplant prognosis in 1,550 adults with primary or secondarymyelofibrosis (MF) undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT) were published in Transplantation and Cellular Therapy by Gagelmann et al. The primary endpoint was 5-year overall survival (OS). 

Key data: The integrated Myelofibrosis Transplant Scoring System (iMTSS) was created across a development (n = 930) and validation (n = 620) cohort. At a median follow-up of 5.6 years, 5-year OS was 61%, with a cumulative non-relapse mortality (NRM) incidence rate of 30% at 5 years. In the iMTSS low-, intermediate-, and high-risk groups, 5-year OS was 72%, 58%, and 39%, respectively, in the validation cohort (p < 0.001); iMTSS outperformed all established prognostic systems (concordance, 0.640; 95% confidence interval [CI], 0.616–0.662). A disease-intrinsic axis, including TP53 allelic state, RAS -pathway mutations, ASXL1, driver genotype, blasts, and blood counts, predicted 2-year relapse incidence (validation concordance, 0.69; 95% CI, 0.63–0.74). A host and structural axis, including portal vein thrombosis, donor type, performance status, and platelet count, predicted 2-year NRM (concordance, 0.63; 95% CI, 0.59–0.68). The two axes were independent and shared 3.4% of their variance (r = 0.18). 

Key learning: In this study, the two-axis iMTSS framework predicted post-transplant prognosis in patients with MF, outperforming all other evaluated prognostic systems. The framework provided risk stratification based on disease and host factors which may potentially inform transplant decision-making and future trial design.