Treosulfan-fludarabine regimen effective after allogeneic HSCT for myelodysplastic syndrome
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SALT LAKE CITY — Treosulfan plus fludarabine conditioning after allogeneic hematopoietic stem cell transplantation conferred better outcomes for patients with myelodysplastic syndrome than a busulfan-based regimen, study results showed.
The results — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR — suggest treosulfan plus fludarabine could be a new treatment option for patients with MDS who are older or who have comorbid conditions.
Rationale and methods
“Our post hoc-analysis was designed to separately analyze patients with MDS who received treatment within a phase 3 study that investigated whether the conditioning combination regimen provides a survival advantage after allogeneic HSCT for elderly and/or comorbid [patients with AML or MDS] compared with the reduced-intensity conditioning regimen of busulfan and fludarabine,” Mathias Stelljes, MD, professor of medicine in the department of medicine and hematology/oncology at University of Muenster in Germany, told Healio.
The analysis included 199 patients (median age, 61 years) with MDS who had a Hematopoietic Cell Transplantation-specific Comorbidity Index greater than 2 or who were aged 50 years or older.
Stelljes and colleagues grouped these patients according to disease risk, donor type and participating institution.
More than half (53%) of patients had high-risk/very high-risk MDS per Revised International Prognostic Scoring System (IPSS-R), whereas 27% had intermediate-risk disease and 20% had low-risk/very low-risk disease.
Researchers randomly assigned patients with matched-related or unrelated donor to 30 mg/m² fludarabine plus either 10g/m² treosulfan or 3.2 mg/kg busulfan.
EFS served as the primary endpoint. Secondary endpoints included OS, relapse/progression incidence, nonrelapse mortality, graft-versus-host disease and chimerism.
Key findings
Neutrophil engraftment occurred at a median 28 days and was comparable between both regimens, according to the researchers.
At day 28, 90% of patients assigned fludarabine-treosulfan and 77% of those assigned fludarabine-busulfan had a complete donor-type chimerism.
At 2 years, researchers reported a higher estimated EFS rate in the treosulfan group (68% vs. 48%; P = .048). Patients assigned the treosulfan-based regimen appeared more likely to be alive (73% vs. 54%) and GVHD-free (45% vs. 34%), and they had a lower cumulative rate of relapse and nonrelapse mortality (20% vs. 29%).
In the subgroup of patients with high-risk/very high-risk disease, results showed significantly better 2-year EFS (67% vs 31%; P = .0132) and OS (76% vs. 37%; P = .0148), as well as a lower rate of nonrelapse mortality (11% vs. 39%; P = .0281), among patients assigned the treosulfan regimen.
Treosulfan also conferred benefit to patients with baseline blast count of 5% or greater with regard to EFS (62% vs 33%; P = .0019) and OS (71% vs. 41%; P = .005).
“These results are not in line with study results from other groups, which indicate that both dose intensity of conditioning regimens and disease status — such as blast counts in the bone morrow prior start of conditioning — are important prognostic factors with regard to survival outcome after allogeneic HSCT,” Stelljes said.
Implications
Given the survival rates between 60% and 70% — even among patients with high-risk MDS and/or higher blast counts prior to start of conditioning — the results suggest treosulfan-based conditioning prior to allogeneic HSCT might mitigate prognostic factors such as MDS disease status and risk category, Stelljes said.
“However, this observation has to be confirmed in future research,” he added. “Transplantation not only relies on donor type, conditioning and GVHD prophylaxis. Other important factors such as policies for tapering of immunosuppression, monitoring of measurable disease/chimerism and treatment of impending relapse are of importance and usually differ between transplant centers and countries. These differences might also explain the differences in survival outcomes.”
Together with other transplant studies, these results demonstrate the substantial curative potential of allogeneic HSCT, even for elderly and/or comorbid patients with MDS, Stelljes said.
“Compared with busulfan-based reduced-intensity conditioning, the treosulfan plus fludarabine regimen showed better survival outcomes, particularly [for] patients with high-risk MDS defined by bone marrow blast count prior transplantation and/or IPSS-R,” he said. “We will now perform a retrospective analysis of patients with MDS who received treosulfan-based conditioning to confirm these findings. A prospective study comparing direct allogeneic HSCT vs. pretreatment followed by allogeneic HSCT might be of interest.”
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Stelljes M, et al. Abstract 42. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.
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