The study also indicated that the type of transplantation donor impacted outcomes following the procedure.
Treating patients with myelofibrosis with ruxolitinib for a short period before they undergo hematopoietic transplantation is associated with a higher likelihood of the procedure occurring, according to results of a phase 2 multicenter trial.
Across the 64 patients included in the trial that had a donor, treatment with ruxolitinib 15 mg for 6 months prior to transplantation led to a 92% chance of transplantation. Twenty (31%) of these patients achieved a partial response before transplantation. All patients received treatment with the Janus kinase inhibitor from time of inclusion in the study to conditioning regimen, or to progression.
At 12 months, 68% of patients were still alive.
“The role of ruxolitinib on post-transplant outcome is difficult to determine, since the trial was not designed to compare patients with and without ruxolitinib,” explained the researchers. “We suspected that progressive ruxolitinib discontinuation before conditioning regimen was associated with higher risk of complication and mortality.”
The researchers did observe that the risk of graft-versus-host disease (GVHD), nonrelapse mortality, and mortality were lower when ruxolitinib treatment was abruptly stopped. However, this finding did not reach significance, potentially a result of the small number of patients.
The study also indicated that the type of transplantation donor impacted outcomes following the procedure. Patients who received transplants from a sibling had superior outcomes than patients with unrelated donors, which could be attributed to several factors, say the researchers.
Patients with a human leukocyte antigen (HLA)-matched sibling donor had a 55% 1-year disease-free survival, compared with 40% for patients with an HLA-matched unrelated donor and 34% for patients with an HLA mismatched unrelated donor.
“Higher mortality in patients who received a transplant from an unrelated donor was due to higher rate of hyperacute and grades 3–4 GVHD,” wrote the researchers, who explained that mortality and GVHD is regularly reported in these patients, which could be a result of several factors like the use of melphalan and the absence of systematical use of anti-thymoglobulin. “In particular, more than 80% of patients transplanted from an HLA mismatched unrelated donor developed grade 3–4 acute GVHD.”
The researchers caveat the finding with a note that inferior survival in patients with an HLA mismatched unrelated donor included 2 patients who never underwent transplantation due to cardiac failure. Of the patients who were transplanted, they did not respond to ruxolitinib, potentially resulting in advanced disease, which the researchers highlight as a potential bias in their study.
Reference
Robin M, Porcher R, Orvain C, et al. Ruxolitinib before allogeneic hematopoietic transplantation in patients with myelofibrosis on behalf SFGM-TC and FIM groups. Bone marrow Transplant. Published March 25, 2021. doi:10.1038/s41409-021-01252-7
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