Phase II Single Center Prospective Study of Ruxolitinib in Addition to Standard Graft Versus Host Disease Prophylaxis in Patients with Myelofibrosis Demonstrates Encouraging Outcomes.

Abstract

Background

In the last decade, hematopoietic cell transplantation (HCT) outcomes in patients with myelofibrosis (MF) have greatly improved. However, the incidence of Grade II-IV acute (74%) and all grades chronic (52%) graft versus host disease (GVHD) with standard GVHD prophylaxis is still high at our Center. In 2019 and 2021, ruxolitinib (Rux), previously only FDA approved for the treatment of MF, was approved for the treatment of steroid refractory acute GVHD and chronic GVHD respectively. Whether Rux is useful in the GVHD prophylaxis setting has only begun to be explored.

Methods

We conducted a Phase II single center prospective study of pre-, peri-, and post-HCT Rux in HCT eligible patients with primary and secondary MF with a primary endpoint of Grade II-IV acute GVHD. Patients had to have at least Dynamic International Prognostic Staging System (DIPSS) Intermediate I stage disease, not have received prior HCT, and not transformed to AML. Patients were treated with at least 8 weeks of planned Rux prior to conditioning chemotherapy (cyclophosphamide 120 mg/kg and targeted 4-day busulfan, or fludarabine 150 mg/m2, and melphalan 140 mg/m2). Rux was then tapered to 5mg BID by Day -4 pre-HCT and could be increased up to 10mg BID after post-HCT Day +28 if tolerated. In addition to Rux, GVHD prophylaxis included tacrolimus (tac) (target level 5-10) and MTX 10mg/m2 on Days 1, 3, 6 and 11; Rux taper started 1 month after completion of tacrolimus and was tapered by month 9 - 12 per clinician discretion.

Results

Twenty-five patients median age 66 (range 42-71) were enrolled on study between 2020-2024. The majority had primary MF (60%), were JAK2 mutated (68%), had intermediate-2 or high-risk DIPSS (72%) and had at least 1 high molecular risk mutation (54%). Most had unrelated donors (76%) and fludarabine/melphalan conditioning (68%). Patients were on Rux for a median of 6 (range 2-24) months prior to conditioning and were continued until a median of 12 (3-34) months post-HCT. 96% of patients engrafted at median Day 20 (range 15 – 26); one patient engrafted at Day 43. Acute GVHD grade II-IV was diagnosed in 36% (n = 9), and grades III-IV in 8% (n = 2); 2 patients required topical therapy only. Rux was held for at least 1 week in 3 patients prior to day 100 resulting in 2 of the 9 cases of GVHD. Chronic GVHD was seen in 12% of patients at 1 year; 2 additional patients developed de novo chronic GVHD at > 1 year once they were off Rux. Kaplan Meier estimates of survival at 1 year and 2 years are 100% and 87% respectively. Relapse and NRM were each seen in 8% (n = 2) of patients.

Conclusions

Compared to patients given standard GVHD prophylaxis at our Center, the incidence of acute and chronic GVHD was considerably reduced in patients who received pre-, peri- and post-transplant Rux. Non-relapse mortality was low and 1- year overall survival was 100%. These data are encouraging, and this strategy will be further pursued.