Progressive substitution of posttransplant cyclophosphamide with bendamustine: A phase I study in haploidentical bone marrow transplantation.

We have initiated a single center phase I study in patients with hematologic malignancies progressively substituting day +4 posttransplant cyclophosphamide (PT-CY) with bendamustine (PT-BEN) following myeloablative conditioning (MAC) and T-cell replete haploidentical bone marrow transplantation (haplo-BMT). We report herein our interim analysis of our first three cohorts PT-CY (mg/kg)/PT-BEN (mg/m): 40/20, 20/60, and 0/90. All patients have tolerated PT-CY/BEN well with no dose limiting toxicities. Compared to contemporaneous controls undergoing haplo-BMT with the same MAC regimens but only PT-CY, we have observed earlier trilineage engraftment (.002 neutrophils, .014 platelets) and a lower incidence of cytomegalovirus reactivation (.016) in the PT-CY/BEN cohorts. After substituting day +4 PT-CY with PT-BEN, the registered trial (www.clinicaltrials.gov; NCT02996773) is proceeding to replace day +3 PT-CY with PT-BEN with a view to identifying further evidence on the potential advantages of PT-BEN.