Outcomes of Myelofibrosis Patients in the Era of Using JAK2 Inhibitor with Allogeneic-HSCT at the University of Southern California

Abstract

Introduction: In myelofibrosis (MF) patients, the standard of care curative option is with allogeneic-hematopoietic stem cell transplantation (allo-HSCT) but no clear standard of care pre- and post-allo-HSCT management exists. Questions then arise such as whether use of JAK inhibitors pre- or post-transplant lead to better outcomes. In addition, further elucidation of patient characteristics/risks/response are needed due to scarcity of data post-transplant. In this study, we aim to provide further data concerning this field. Methods: This retrospective chart review included patients aged 18 years with MF diagnosed in 2012-2020 and received allo-HSCT at our institution. Primary objectives include over-all survival (OS) and progression-free-survival (PFS) since transplant, stratified by risk, peri-transplant JAK2 inhibitor use and conditioning + associated graft versus host disease prophylaxis (GVHD ppx) use. Secondary objectives include patient/treatment/transplant characteristics, response, survival and GVHD rates. Two-sided p value ≤ 0.05 was significant. RESULTS: 21 screened MF patients received allo-HSCT at our institution, median age 61.1 years (85.7% non-Hispanic and 14.3% Hispanic). 71.4% had primary MF. 9.5% had unfavorable/high risk karyotype/cytogenetics with 38.1% at high risk per Dynamic International Prognostic Scoring System (DIPSS) Plus, and 38.1% high risk, 28.6% very high-risk per Mutation-Enhanced International Prognostic Score System (MIPSS) 70+ v2.0. 52.4% had JAK2 V617F mutation, 28.6% triple negative (lacked JAK2/MPL/CALR mutations) with 23.8% as having any positivity in either ASXL1, EZH2, SRSF2, IDH1/2 and U2AF1 mutations. Pre-transplant, 100% had pancytopenia requiring transfusions. 9.5% had CR/PR, 42.9% had PD and 47.6% had SD. Of note, 57.9% had any peri-transplant JAK2 inhibitor use (defined as use within 3 months pre- and post-transplant) with or without other MF related-treatments. 33.3% underwent MSD, 38.1% MUD and 28.6% underwent HAPLO allo-HSCT. 80% had reduced intensity conditioning (RIC) with an equal distribution of fludarabine-based regimens. In terms of GVHD ppx, 55% received tacrolimus+ methotrexate and 35% had post-transplant cyclophosphamide (PTCY). 30% underwent HAPLO + PTCY. In terms of outcomes and adverse events, pancytopenia improved from 90.5% at d+30 to 57.1% at d+365. Transfusion dependency decreased from 60% from d+90 to 26.7% by d+365. None had leukemic transformation. Clinical improvement rates increased from 33.3% d+30 to 78.6% by d+365. CR/PR rate increased from 5% at d+90 to 28.6% at d+365. 14.3% had relapsed/PD, 37.5% had primary graft failure with 33.3% any deaths post allo-HSCT. 42.9% had any acute GVHD pre-d+100, 42.1% had any chronic GVHD post d+100. Of note, 100% of our population were alive at d+100, and 78.9% alive by d+365. Since transplant, 3y OS was 62.6%, 3y EFS at 59.2% with corresponding worsening of OS/EFS with higher DIPSS (p=0.19-0.33) and a 3y OS (40%) (p=0.29) and EFS (40%) (p=0.41) in patients with very-high risk per MIPSS 70+ v2.0. With peri-transplant JAK2 inhibitor use, 3y OS was 56.8% vs 75% without; 3y EFS was 51.1% vs 75% without (p=0.33-0.51) (Fig.1). For patients who underwent HAPLO+PTCY GVHD ppx, OS and EFS reached at 16 months while patients who underwent non-HAPLO+ any GVHD ppx did not reach their median OS yet and achieved an EFS median of 57 months. 2y OS and EFS was at 50% for those who underwent HAPLO+PTCY vs a 67.1% OS and a 61.9% EFS for those who had non-HAPLO+ any GVHD ppx (p=0.51-0.72) (Fig.2). CONCLUSIONS: Given that most of our patients had high/very high-risk scores, we achieved a good rate of clinical improvement with less transfusion dependency. A good survival rate was also achieved (100% survival at d+100 and 78.9% at 1y). Our 3y OS of 62.6% and 3y EFS of 59.2% is also appreciable even with the rates of GVHD. Our data also further supports that having a higher risk score per DIPSS/MIPSS leads to poorer survival. Interestingly, there may be no difference in OS/EFS with peri-transplant JAK2 inhibitor use. Also, those who underwent HAPLO+PTCY had their median OS/EFS reached first (16 months) with a possible lower survival trend compared to those who underwent MSD/MUD + any GVHD ppx combination treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal