Selinexor Combined with Reduce Intensity Conditioning of BU/CY for Allogeneic HSCT in Elderly Patients with Relapsed/Refractory AML/MDS
Authors: Ni Xiaofei , Zhang Rongli , Jiang Erlie 
Published: December 2024

Objective: To investigate the safety and efficacy of a modified busulfan (Bu)/cyclophosphamide (Cy) conditioning regimen incorporating Selinexor for allogeneic hematopoietic stem cell transplantation in elderly patients with relapsed/refractory hematologic malignancies.

Methods: We retrospectively evaluated the clinical outcomes of patients aged 50 and above with hematologic malignancies who had received allo-HSCT with conditioning incorporating Selinexor at the Institute of Hematology and Blood Disease Hospital.

Results: Between September 2022 and March 2024, 25 elderly patients with high-risk hematologic malignancies were enrolled including 13 males and 12 females with a median age of 55 (50-67) years (Table 1). There were 10 patients with acute myeloid leukemia (AML), 14 with myelodysplastic syndromes (MDS), 1 with MDS/MF.

Nine patients were in complete remission (CR), six in CR1, three in ≥CR2, four in non-remission (NR), and five patients were in a progressive disease status (PD) prior to conditioning. One patient received matched-sibling donors transplant, one patient received unrelated donor transplant, while 23 patients received related haploid hematopoietic stem cell transplantation.

All patients had received myeloablative conditioning regimen incorporating Selinexor: Bu (3.2mg/kg/d*2d); Melphalan (Mel, 60mg/m2/d*2d), Cladribine (CLA, 5mg/m2/d*3d), Cyclophosphamide (Cy, 40mg/kg/d*2d), Selinexor 60mg/d*2d. The median amount of infused mononuclear cell and CD34+ stem cell was 11.72×108/kg (range, 8.83 to 21.27) and 5.033×106/kg (range, 1.695 to 9.78), respectively.

All the 25 patients achieved neutrophil engraftment with a median time of 12 (range, 10 to 22) days and 23 patients achieved platelet engraftment with a median time of 13 (range, 10 to 51) days. Two patients were still experiencing prolonged isolated thrombocytopenia.

All patients achieved complete donor chimerism and minimal residual disease (MRD) negative at 30 days post-transplantation.The cumulative incidence of cytomegalovirus (CMV) reactivation was 24%, while the cumulative incidence of Epstein-Barr virus (EBV) reactivation was 8%. Mucosal barrier injury occurred in 9 patients (36%), primarily presenting as oral mucosal ulcers and hemorrhagic cystitis. The cumulative incidence of grade 0-II and grade III-IV acute graft-versus-host disease (GVHD) was 12% and 16%, respectively. Two cases (8%) of patients experienced mild chronic GVHD.

The median follow-up for all the participants was 313.5 (124-606) days after transplantation. The overall survival (OS) rates at 6 months and 1 year are 88.8% ± 7.6% and 59.6% ± 15.2%, respectively. The cumulative relapse rates at 6 months and 1 year are 20% ± 8% and 39% ± 13.3%, respectively. The relapse-free survival (RFS) rates at 6 months and 1 year are 68.1% ± 10.3% and 51.9% ± 12.8%, respectively. The cumulative transplant-related mortality (TRM) rates at 6 months and 1 year are both 11.5% ± 7.6%(Figure 1).

Conclusions: Incorporating Selinexor into the modified BU/CY conditioning regimen for allogeneic HSCT in elderly patients with relapsed/refractory hematologic malignancies demonstrated a favorable safety profile. Ongoing prospective trials will provide valuable insights into the potential benefits of Selinexor in patients undergoing HSCT.