Peri-Transplant Ruxolitinib Is Safe for Patients with Myelofibrosis

By Kerri Fitzgerald - Last Updated: March 3, 2021

A study presented at the 2021 Transplantation and Cellular Therapy Meetings found that peri-transplant ruxolitinib was safe and well tolerated in older patients with myelofibrosis (MF).

The prospective pilot trial included 18 patients. Ruxolitinib treatment was assessed at two dose levels: 5 mg (DL1; n=6) and 10 mg (DL2; n=12), given twice daily for up to 100 days, starting three days prior to transplant.

Median age at hematopoietic cell transplant (HCT) was 65 years (range, 25-73 years) overall, 53 years (range, 25-66 years) in the DL1 cohort, and 69 years (range, 55-73 years) in the DL2 cohort. According to the Dynamic International Prognostic Scoring System, four patients were high risk, while 14 were intermediate risk. Time from diagnosis to initial treatment was 17 months (range, 2.7-74.2 months), and median time from diagnosis to HCT was 17.2 months (range, 3.0-74.5 months). Patients had the following driver mutations: JAK2 (n=9), MPL (n=1), and CALR (n=4); four patients were triple-negative.

All patients achieved engraftment with neutrophil recovery: Patients in the ruxolitinib 5 mg arm achieved engraftment within 19 days (range, 13-23 days) and patients in the ruxolitinib 10 mg cohort achieved engraftment within 16 days (range, 12-22 days). At each dose level, one patient developed a dose-limiting toxicity (DLT): one grade 3 cardiac and gastrointestinal DLT and one grade 4 pulmonary DLT occurred in the 5 mg cohort and one patient experienced grade 3 kidney damage in the 10 mg group.

Cumulative incidence of acute graft-versus-host disease (GVHD) grade II-IV and III-IV were 17% (95% confidence interval [CI], 6-47) and 11% (95% CI, 3-41), respectively. Cumulative incidence of one-year chronic GVHD was 42% (95% CI, 24-74).

After a median follow-up of 22.6 months (range, 6.2-25.8 months) among surviving patients, one-year overall survival and progression-free survival were 77% (95% CI, 50-91) and 71% (95% CI, 44-87), respectively. At one year, cumulative incidence of relapse was 6% (95% CI, 1-40) and non-relapse mortality was 23% (95% CI, 10-54).

Four deaths occurred due to cardiac arrest, GVHD, respiratory failure, and refractory GVHD of the liver.

“Our results showed that peri-HCT ruxolitinib was safe and well tolerated, with the maximum tolerated dose determined as 10 mg twice daily, associated with dose-dependent pharmacokinetics and cytokine profile,” the researchers concluded.

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