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, of Dana-Farber Cancer Institute, and colleagues at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition, reduced-intensity allogeneic hematopoietic stem cell transplant from compatible donors improved the survival rate of patients aged 50 to 75, without compromising quality of life (Abstract 75). At 3 years, 48% of patients for whom donors were identified were alive, compared with 27% without donors.

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.

Corey Cutler, MD, MPH

Robert A. Brodsky, MD

“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,” said Dr. Cutler in a press briefing prior to his presentation.

Press briefing moderator Robert A. Brodsky, MD, ASH Secretary and Professor of Medicine and Oncology and Director of the Division of Hematology at Johns Hopkins School of Medicine, 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

BMTCTN 1102 was a multicenter study that involved 384 patients who were referred to transplant centers, which searched for suitable stem cell donors for them. Assignment to hematopoietic stem cell transplant (HCT) or no transplant was based on high-resolution typing to identify 8/8 human leukocyte antigen (HLA)-matched related or unrelated donors.

Enrolled patients were age 50 to 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, performance status, disease stage, comorbidities, IPSS score, MDS duration, and response to hypomethylating agents.

Investigators also analyzed 3-year leukemia-free survival; 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 were also conducted. Additionally, researchers analyzed quality of life and cost-effectiveness.

The 260 patients who were matched with a donor within 90 days were assigned to undergo HCT; the other 124 patients received standard supportive care—mainly, treatment with hypomethylating agents.

Survival Benefit With Transplant

Approximately 3 years after enrolling in the trial, 47.9% of patients slated for transplant were alive, compared to 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 in both the 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, yielding odds ratios of 2.398 for patients younger than 65 and 2.206 for patients age 65 or 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 one in spite of their assignment to the no-donor group. Therefore, the investigators conducted the as-treated analysis to ascertain outcomes in those patients who did undergo transplant, regardless of 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

While quality-of-life factors will be fully analyzed later in the study, at this point, no significant differences were seen between the transplant and no-transplant groups. Patient-reported outcomes were assessed via the FACT-G 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 dataset once all the 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 following transplant,” he said.

Transplant Not Covered by Medicare

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. While 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 has declined reimbursement.

“We hope, with results of this trial showing a definitive overall survival benefit without detriment in quality of life, that the Centers for Medicare and Medicaid Services will reconsider its decision regarding not paying for this service,” he said. 

The study authors concluded, “We observed a significant overall survival advantage in older patients with IPSS intermediate-2 and high IPSS risk de novo MDS who are reduced-intensity conditioning HCT candidates and have an HLA-matched donor, when compared with those without a donor. The benefit of having a matched donor was seen across subgroups, including those who were of Medicare age (> 65 years) and below. HCT should be offered to all individuals between the ages of 50-75 with intermediate-2 and high IPSS risk MDS in whom a suitable donor can be identified.”

Disclosure: For full disclosures of the study authors, visit ash.confex.com.