Transplant May Improve Survival in Older Patients With High-Risk Myelodysplastic Syndrome, Study Reports

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Stem cell transplants are not frequently offered to older patients with high-risk myelodysplastic syndromes (MDS). According to a study from the Blood and Marrow Transplant Clinical Trials Network (BMTCTN 1102), these patients may indeed achieve a survival benefit from stem cell transplant.

As reported by Corey Cutler, MD, MPH, FRCPC, of Dana-Farber Cancer Institute, Boston, at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition, subjects between the ages of 50 and 75 with HLA-compatible donors had nearly a doubled survival rate, without compromising quality of life.1 At 3 years, 48% of patients for whom donors were identified were alive, compared with 27% without donors.

“The results of our study should allow all patients [with myelodysplastic syndrome] who are potentially eligible for transplant to have a meaningful conversation about it.”
— Corey Cutler, MD, MPH, FRCPC

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In an as-treated analysis of patients who actually underwent transplant, the benefit was even greater. Transplants also led to more patients being free of leukemia at 3 years, Dr. Cutler reported.

“It is critical in myelodysplasia that patients are at least offered a chance for transplantation…. The results of our study should allow all patients who are potentially eligible for transplant to have a meaningful -conversation about it,” Dr. Cutler said in a press briefing prior to his -presentation.

ASH spokesperson Robert A. Brodsky, MD, Head of Hematology at Johns Hopkins School of Medicine, Baltimore, considered the results to be practice changing. “Bone marrow transplant will be the standard of care, rather than drug therapy, for those high-risk patients with MDS who can receive a transplant,” he said.

Study Design

The multicenter study involved 384 patients who were referred to transplant centers, which searched for suitable stem cell donors. Assignment to the donor or no-donor group was based on high-resolution typing to identify eight of eight HLA-matched related or unrelated donors.

The patients were between the ages of 50 and 75, had primary intermediate-2 or high-risk MDS by the International Prognostic Scoring System (IPSS), and were candidates for traditional reduced-intensity transplantation. The primary endpoint was adjusted 3-year overall survival, to account for the potential bias that could result from the biologic assignment. Adjustments were made for age, sex, gender, performance status, disease stage, comorbidities, IPSS score, MDS duration, and response to hypomethylating agents.

“Bone marrow transplant will be the standard of care, rather than drug therapy, for those high-risk patients with MDS who can receive a transplant.”
— Robert A. Brodsky, MD

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Investigators also analyzed 3-year leukemia-free survival. They conducted a sensitivity analysis that excluded subjects who died or withdrew before finding a donor during the 90-day search period and an as-treated analysis. Quality of life and cost-effectiveness were also analyzed.

The 260 patients who were matched with a donor within 90 days were assigned to undergo hematopoietic stem cell transplant (HCT). The other 124 patients received standard supportive care, mainly treatment with hypomethylating agents.

Survival Improved With Transplant

Approximately 3 years after enrolling in the trial, 47.9% of those slated for transplant were alive, compared with 26.6% of those for whom no donor was found. The absolute improvement in overall survival was 21.3% (P = .0001), Dr. Cutler reported.

In the subgroup analysis, there were no significant differences in treatment effects on survival for any subgroup, including, importantly, patients older and younger than age 65. The odds of surviving at 3 years were more than double in the donor group for both younger (odds ratio [OR] = 2.436) and older (OR = 2.962) patients. All other subgroups derived benefit from HCT.

Similarly, leukemia-free survival was significantly higher in the donor arm (35.8%) than in the no-donor arm (20.6%; P = .003). The sensitivity analysis was consistent, again, yielding odds ratios of 2.398 for patients younger than age 65 and 2.206 for patients aged 65 and older.

Other Transplant Outcomes

Approximately one-quarter of patients did not conform to their assignment, either failing to undergo transplant for a variety of reasons or undergoing an alternative donor transplant despite their assignment to the no-donor group. Therefore, the investigators conducted the as-treated analysis to ascertain outcomes in those patients who followed their treatment assignment. This showed an even greater survival advantage, with absolute improvements of 31.4% for overall survival (P < .0001) and 28.4% for leukemia-free survival (P < .0001), Dr. Cutler reported.

No Compromise in Quality of Life

Although quality-of-life factors will be fully analyzed later in the study, no significant differences were seen between the -donor and no-donor groups at this point. Patient-reported outcomes were assessed via the Functional Assessment of Cancer Therapy: General total score, SF-36 Physical and Mental Components, and EQ-5D. At all timepoints, outcomes were similar between donor and no-donor arms except for two measures at one time point each, which did not reflect clinically meaningful differences, according to Dr. Cutler.

“We plan to reanalyze the complete quality-of-life data set once all data collection is complete, but this early analysis demonstrates clearly that early transplant for higher-risk MDS is not associated with a decrement in quality of life shortly after transplant,” he said.

Will Medicare Rethink Decision on Reimbursement?

Part of the impetus for the 34-center trial was to provide a rationale for insurance coverage of transplants in older individuals, according to Dr. Cutler. Although allogeneic transplant has been shown to improve survival in numerous studies, its benefit in older patients has not been proven; thus, the Centers for Medicare and Medicaid Services (CMS) currently only reimburses for transplant services when patients are participating in clinical trials, including a large registration study being conducted through the Center for International Blood and Marrow Transplant Research.

“With the results of this trial showing a definitive overall survival benefit without detriment in quality of life, we hope CMS will reconsider its decision regarding payment policies,” he said. 


DISCLOSURE: Dr. Cutler has served as a consultant or advisor to Mesoblast, Generon, Medsenic, Jazz Pharmaceuticals, Kadmon, and Incyte. Dr. Brodsky has served on an advisory board for Achillion Pharmaceuticals; has received research funding from Achillion Pharmaceuticals and Alexion Pharmaceuticals; has served as a consultant to Alexion Pharmaceuticals; and has received honoraria from UpToDate.


1. Nakamura R, Saber W, Martens MJ, et al: A multicenter biologic assignment trial comparing reduced intensity allogeneic hematopoietic cell transplantation to hypomethylating therapy or best supportive care in patients aged 50–75 with advanced myelodysplastic syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102. 2020 ASH Annual Meeting & Exposition. Abstract 75. Presented December 5, 2020.