Objectives

To determine whether having a suitable HLA-matched donor improves outcomes for older patients with higher-risk myelodysplastic syndrome who are candidates for reduced-intensity allogeneic stem-cell transplantation.

Background

Myelodysplastic syndrome (MDS) is predominantly a disease of older adults. Treatment with DNA hypomethylating agents can improve hematologic parameters, reduce transfusion requirements, delay transformation to acute myelomonocytic leukemia (AML), and prolong progression-free survival and overall survival (OS) in individuals with higher-risk disease. However, fewer than half of the patients with MDS achieve objective responses to hypomethylating therapy, and these responses are usually of limited duration. Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for MDS and an established therapy for younger patients with MDS. Allogeneic HCT does carry the risk of early transplant-related mortality. Although transplantation outcomes among selected older individuals with MDS are similar to those in younger patients with MDS, early transplantation for older individuals is not broadly accepted. Statistical modeling analyses demonstrate the benefits of early HCT in older populations, and two prospective studies from European groups showed a benefit of HCT over non-HCT therapy when a suitable donor is available. The BMT CTN-1102 clinical trial was designed to evaluate the relative benefits of reduced intensity conditioning (RIC) allogeneic HCT compared to non-transplant therapies in older patients.

Participants

All subjects were required to have been diagnosed with de novo intermediate-2 or high-risk MDS by IPSS criteria. Eligible subjects were between 50 and 75 years of age and candidates for RIC HCT from an HLA-matched related or 8/8 HLA-matched unrelated donor.

A total of 260 patients were enrolled in the Donor arm, and 124 patients were enrolled in the No-Donor arm.

Design

The BMT CTN-1102 study was an open-label, multicenter, biologic assignment trial. Biologic assignment was to a Donor or No-Donor arm based on high-resolution HLA typing of eligible family members and a 90-day search of the unrelated donor registry through the National Marrow Donor Program. Subjects assigned to the Donor arm were expected to undergo RIC HCT within 6 months of enrollment, whereas those assigned to the No-Donor arm were expected to receive non-HCT therapy or best supportive care. Both the RIC HCT regimen and non-transplant therapy/best supportive care were at the discretion of the treating physician.

Quality-of-life (QOL) measures were collected at enrollment, as well as at 6, 12, 18, 24, and 36 months. The post-transplant outcomes of disease-free survival, relapse, treatment-related mortality (TRM), and acute and chronic graft-versus-host disease (GVHD) are described through 27 months post-HCT.

The primary end point was 3-year overall survival. Secondary end points included 3-year leukemia-free survival, QOL measures, and cost effectiveness.

Conclusions

There was a significant 3-year overall survival advantage in older MDS subjects who were RIC HCT candidates with matched donors identified when compared with those without a donor. Based on this study, HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.

Nakamura R, Saber W, Martens MJ, et al. Biologic Assignment Trial of Reduced-Intensity Hematopoietic Cell Transplantation Based on Donor Availability in Patients 50-75 Years of Age With Advanced Myelodysplastic Syndrome. J Clin Oncol. 2021;39(30):3328-3339. doi:10.1200/JCO.20.03380

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