Organ Involvement, GVHD Severity Predict Ruxolitinib Failure in Chronic GVHD

In updated results from a real-world analysis presented at the 2021 ASH Annual Meeting, researchers confirmed that ruxolitinib is an effective treatment option for patients with chronic graft-versus-host disease (GVHD) but also identified factors prognostic of ruxolitinib failure.

The results were shared in a poster by Jennifer White, MD, MSc, FRCPC, from the British Columbia Cancer Agency and Vancouver General Hospital in Canada.

Study authors previously reported a real-world experience of ruxolitinib in 47 patients with cGVHD, with a six-month overall response rate (ORR) of 36%. The present study expanded this cohort to include 115 patients, evaluating ORR, failure-free survival (FFS) and overall survival (OS). Investigators also explored prognostic factors associated with clinical outcomes.

Participants’ median age at enrollment was 57.5 years. Sixty-nine patients (60%) had severe cGVHD and 44 (38.3%) had moderate cGVHD. Of the 108 patients with available HCT-CI scores prior to transplant, 29 (26.9%) had HCT-CI score ≥3 and 79 (73.1%) had HCT-CI score 0-2. The median number of organ involvement was three, with skin and mouth as the most common sites of organ involvement.

Ninety-six patients (84.2%) received ruxolitinib as the fourth line of therapy or later. The most common prior treatments were mycophenolate mofetil, extracorporeal photopheresis, imatinib, and ibrutinib. Ruxolitinib was started at 10 to 20 mg daily as the initial dose, then maintained at 20 mg daily in two divided doses on months three, six, and 12.

ORR was 46.8%, 61.8%, and 62.3% at three, six, and 12 months. Six-month ORRs in the range of 48.1% to 64.5% were observed across all the organ sites involved. The authors found no difference in ORR between patients with steroid-resistant and steroid-dependent cGVHD, or according to previous treatment with a tyrosine kinase inhibitor for GVHD.

Researchers observed 39 cases of treatment failure, for a rate of 33.4%, including resistance requiring switch to other therapy (n = 17), non-relapse mortality (n = 14), relapse of primary disease (n = 3), and ruxolitinib intolerance (n = 5). At 12 months, the FFS rate in the overall population was 64.6%, while the OS rate was 83.3%.

In their analysis of risk factors associated with FFS, they identified two significant factors:

  • Severe grade cGVHD at ruxolitinib initiation (hazard ratio [HR] = 2.496; p = 0.008).
  • Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) score ≥3 (HR = 2.802; p = 0.001).

When they generated a risk score model, the authors found that the model stratified patients according to FFS risk at 12 months: 85.8% for score 0 (n = 32); 58.7% for score 1 (n = 57); and 36.8% for score 2 (n = 19).