The use of a JAK inhibitor prior to allogenic hematopoietic stem cell transplantation (alloHSCT) appears to be effective for patients with myelofibrosis, according to a study presented at the BMT Tandem Meetings (February 21-25, 2018; Salt Lake City, UT).
Rachel B Salit, MD, Fred Hutchinson Cancer Research Center, Seattle Care Cancer Alliance, and colleagues conducted a study to determine the effects of ruxolitinib—a JAK inhibitor—in the pre-transplant setting on patients with myelofibrosis,.
The primary endpoint of the study was 2-year post-transplant survival. Graft failure, 1-year relapse, and incidence of graft-versus-host disease (GVHD) served as secondary endpoints.
A total of 28 patients were included in the two-part trial. Candidates for the trial were patients with primary (n=15) or secondary (n=13) myelofibrosis who received ruxolitinib for a minimum of 8 weeks prior to alloHSCT. The median patient age was 56 years.
Patients agreed to transplant and ruxolitinib treatment tapered over 1 to 2 weeks through day four of conditioning. Patients received conditioning per provider choice with 120 mg/m2 fludarabine and 140 mg/m2 melphalan (n = 3) or 120 mg/kg cyclophosphamide and 16 mg/kg busulfan (n = 19).
Donor sources included 14 related, five unrelated, and three double cord blood grafts. Those who underwent transplant with cord blood received 75 mg/m2 fludarabine in addition to cyclophosphamide/busulfan conditioning.
Researchers noted that prior to JAK inhibitor treatment, one patient was deemed low risk, seven were intermediate-1 risk, and 14 patients were intermediate-2 risk.
The median follow-up was 12.5 months. All patients were engrafted at a median of 19 days (range 14-35). No incidence of cytokine release syndrome occurred and no graft failures were observed. Results showed the median chimerism at day 80 was 88% for CD3 and 100% for CD33.
Researchers observed chronic GVHD in six out of 17 evaluable patients, two of which cases were severe. The incidence of acute GVHD at grade 2-4 was 70% and at grade 3-4 was 15%. The 1-year survival rate was 93% (95% CI, 0.73-0.98) and 2-year survival was 86% (95% CI, 0.61-0.96).
Overlapping a JAK inhibitor with conditioning chemotherapy proved to be safe in patients with myelofibrosis and prevented cytokine release syndrome. However, authors noted that more research is needed to confirm this finding due to the small sample size of their study.—Janelle Bradley