Allogeneic hematopoietic cell transplantation with a combination of posttransplantation bendamustine and cyclophosphamide in refractory myeloid neoplasms.

Abstract

Prognosis after salvage allogeneic hematopoietic cell transplantation (HCT) in refractory myeloid malignant diseases is poor with no standard of care. A prospective single-arm study was conducted to evaluate if a combination of posttransplantation bendamustine and cyclophosphamide (PTBCy) facilitates augmented graft-vs-leukemia effect in this group of patients. The prospective study (NCT04943757) of HCT from all types of donors enrolled 50 patients with refractory myeloid neoplasms. Cumulative incidence of engraftment was 88%; 76% had no measurable residual disease. Immune toxicity in the form of cytokine release syndrome was observed in 30%. Cumulative incidence of acute graft-vs-host disease (GVHD) Grade 2 through 4 was 20%. Cumulative incidence of moderate and severe chronic GVHD was 34%. Nonrelapse mortality was 20%. Relapse incidence was 62%, but median time to relapse was 245 days. Overall survival was 33% and event-free survival was 22%. In the multivariate analysis of event-free survival alternative donor (hazard ratio, 0.24; 95% CI, 0.11-0.52) and adverse genetic features (hazard ratio, 2.48; 95% CI, 1.26-4.88) were significant. PTBCy regimen was associated with unique immune reconstitution pattern with high levels of CD8+ effector memory T cells, PD-1L-positive monocytes, and granulocytes. PTBCy GVHD prophylaxis is a promising approach for refractory myeloid neoplasms, which delays relapse after HCT and opens the window for posttransplant prophylaxis.