Patients who received MBTF prior to allo-HSCT achieved promising survival outcomes and manageable safety in relapsed/refractory acute myeloid leukemia.
The conditioning regimen of mitoxantrone hydrochloride liposome, thiotepa, busulfan, and fludarabine (MTBF) before salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) produced promising, durable efficacy in patients relapsed/refractory acute myeloid leukemia (AML), according to data from a prospective clinical trial (NCT06385808).1
Data published in Cell Transplantation showed that at a median follow-up of 15 months (range, 7-27) patients who received MTBF leading up to transplantation (n = 24) achieved a 2-year cumulative incidence of relapse (CIR) rate of 10% (95% CI, 0-27). One-year overall survival (OS) and progression-free survival (PFS) rates were 94.4% ± 5.4% (95% CI, 84.4%-100%) and 82.0% ± 13.2% (95% CI, 59.8%-100%), respectively.
Moreover, within 100 days of receiving allo-HSCT, 9 patients experienced any-grade graft-vs-host disease (GVHD), including 5 cases of grade 2 acute GVHD, 3 cases of grade 3 GVHD, and 1 case of grade 4 GVHD. The median onset time of acute GVHD among patients was 39 days (range, 12-90) with chronic and severe GVHD rates being 41.67% and 8.33%, respectively.
“This study provides a novel and promising conditioning regimen for R/R AML patients received salvage allo-HSCT, with the incorporation of mitoxantrone liposome being a core highlight of the regimen design,” Juan Ren, MD, of the Department of Hematology at The First Affiliated Hospital of Xi’an Jiaotong University in China, and coauthors wrote in a publication of the data.
What was the design of the trial evaluating MTBF in relapsed/refractory AML?
The single arm study enrolled patients who were at least 18 years of age and no older than 65 years with a bone barrow blast cells level higher than 5%, extramedullary disease, or leukemic blast cells found in the peripheral blood following 2 cycle of standard induction therapy. Patients must also not be able to achieve a complete response via chemotherapy and be eligible for allo-HSCT.2
If patients had hypersensitivity to investigational treatments, uncontrolled systemic diseases, cardiac disease, active hepatitis B or C infections, other malignant tumors, or human immunodeficiency virus infections, they were not enrolled in the study.
Patients received a 24 mg/m2 per day intravenous (IV) infusion of mitoxantrone hydrochloride liposome one week before transplantation followed by 5 mg/m2 per day IV infusions of thiotepa on 6 and 5 days prior to transplantation.1 Then, from 4 to 2 days prior to transplantation, patients received 3.2 mg/m2 per day IV infusions of busulfan and 50 mg/m2 per day IV infusions of fludarabine.
Two-year CIR rate was the primary end point of the study; 1-year PFS and OS rates, GVHD, and safety as key secondary end points.
Baseline characteristics revealed that patients had a median age of 39 years (range, 18-70) and were mostly male (54.17%). Most patients also had primary AML (70.8%), relapsed disease status (66.67%), a European LeukemiaNet cytogenetic/molecular risk that was poor (41.67%), and normal chromosome karyotypes (70.83%). The most common molecular biology and HCST type for patients were FLT3-ITD-mutated disease (37.5%) and haploidentical-HSCT (HID; 66.67%). Regarding bone marrow blast cell rates, patients had 5% to 20% (29.17%), 20% to 75% (45.83%), or extramedullary (25%).
What additional data was shown for MBTF before allo-HSCT in R/R AML?
Two-year OS and PFS rates were 78.9% ± 11.1% (95% CI, 59.9%-100%) and 51.2% ± 19.3% (95% CI, 24.5%-100%), respectively. Additionally, patients who received maintenance therapy following allo-HSCT (n = 8) achieved a 2-year OS rate of 100% compared with 50% in those who did not receive maintenance (n = 16; log-rank P = .041).
Further subgroup analyses revealed that patients with higher than 20% blast cells in bone marrow prior to transplantation, active extramedullary disease, and risk stratification at diagnosis did not result in significantly different outcomes vs the overall population. No significant differences when compared with the overall population were shown for OS, PDS, and CIR rates with patients who received matched sibling donor transplantation and HID-HSCT.
In terms of safety, all patients achieved hematopoietic recovery, median time to neutrophil reconstitution was 11 days (range, 9-13), and the median time to platelet reconstitution was 12 days (range, 9-23). One-year post transplantation infections rates were 29.17% with the most common types of infections being pulmonary (25%) and intestinal (10.3%). Common non-hematologic toxicities experienced by patients in the trial were nausea (66.7%), diarrhea (50%), mucositis (50%), gastrointestinal bleeding (20.83%), elevated aspartate aminotransferase (17%), and skin discoloration (16.67%). Finally, patients in the trial demonstrated a non-relapse mortality rate of 8.33% within 6 months.
“Our primary findings confirm that this regimen was a safe and effective conditioning regimen for [patients with] relapsed/refractory AML with poor prognosis,” study authors concluded.
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