In a study reported in the Journal of Clinical Oncology, Nakamura et al found that use of reduced-intensity conditioning allogeneic hematopoietic cell transplantation (HCT) in older patients with advanced myelodysplastic syndrome (MDS) with an available matched donor improved overall survival vs hypomethylating therapy or best supportive care in patients not receiving HCT due to absence of a matched donor.
Study Details
In the U.S. multicenter trial, 384 patients aged 50 to 75 years with intermediate-2 or high-risk de novo MDS were enrolled between January 2014 and November 2018. Patients were assigned to the donor group (n = 260) or no-donor group (n = 124) based on availability of a matched donor (human leukocyte antigen [HLA]-matched related or 8/8 HLA-matched unrelated) within 90 days of study registration. Patients in the donor group received reduced-intensity conditioning HCT. Patients in the no-donor group received hypomethylating therapy or best supportive care. The primary outcome was overall survival probability at 3 years, with analysis adjusted for age, race/ethnicity, performance status, disease status, comorbidity index, International Prognostic Scoring System score, MDS disease duration, and response to hypomethylating therapy.
We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.— Nakamura et al
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Key Findings
Median follow-up for surviving patients was 34.2 months (range = 2.3–38 months) in the donor group and 26.9 months (range = 2.4–37.2 months) in the no-donor group.
In intention-to-treat analysis, the adjusted 3-year overall survival rate was 47.9% (95% confidence interval [CI] = 41.3%–54.1%) in the donor group vs 26.6% (95% CI = 18.4%–35.6%) in the no-donor group (absolute improvement = 21.3%, 95% confidence interval [CI] = 10.2%–31.8%, P = .0001; odds ratio for survival = 2.76, 95% CI = 1.59–4.81). A survival benefit in the donor group was observed across all subgroups examined.
In intention-to-treat analysis, leukemia-free survival at 3 years was 35.8% (95% CI = 29.8%–41.8%) in the donor group vs 20.6% (95% CI = 13.3%–29.1%) in the no-donor group (absolute improvement = 15.2%, 95% CI = 13.3%–29.1%, P = .003).
A total of 44 patients (17%) in the donor group did not undergo HCT, and 26 (10%) received myeloablative HCT. A total of 31 patients (25%) in the no-donor group underwent HCT, including 9 from a matched donor identified after the 90-day search period; all others received alternative donor transplant (mismatched unrelated, haploidentical, or umbilical cord blood), including 6 who received myeloablative conditioning. In an as-treated analysis, 3-year overall survival was 47.4% vs 16.4% (P < .0001) and 3-year leukemia-free survival was 39.3% vs 10.9% (P < .0001).
The investigators concluded, “We observed a significant survival advantage in older subjects with higher-risk MDS who have a matched donor identified and underwent reduced-intensity HCT, when compared with those without a donor. HCT should be included as an integral part of MDS management plans in fit older adults with higher-risk MDS.”
Corey Cutler, MD, MPH, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Heart, Lung, and Blood Institute and National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
