Post-transplant cyclophosphamide (PT-CY) is the most widely applied graft-versus-host disease (GvHD) prophylaxis regimen in T-cell replete haploidentical bone marrow transplantation (haplo-BMT). While PT-CY has been met with great success in the haplo-BMT arena by suppressing GvHD, patients without acute GvHD have high relapse rates.
One of the strategies being explored by others to lessen relapse rates is the dose reduction of PT-CY. We have taken a different approach in evaluating whether partially replacing PT-CY with post-transplant bendamustine (PT-BEN) would be advantageous, which is based on our pre-clinical research that delineated several beneficial immunomodulatory properties of BEN.
We therefore initiated and completed a Phase Ia trial which evaluated the progressive substitution of PT-CY with PT-BEN (NCT02996773). Thirteen patients with high-risk hematologic malignancies have received PT-CY/BEN and their outcomes compared to 31 contemporaneous haplo-BMT recipients treated with the same myeloablative conditioning (MAC) regimens but receiving only PT-CY.
We demonstrate that partial replacement of PT-CY with PT-BEN on day +4 (PT-CY/BEN) is well tolerated and associated with significantly earlier trilineage engraftment. We also show favorable trends to significant improvements in univariate and multivariate analyses, with PT-CY/BEN compared to PT-CY, with respect to chronic GvHD (HR, 0.08; 95% CI, 0.005, 1.11; P=0.06), and GvHD-free-relapse-free survival (GRFS) (HR, 0.22; 95% CI, 0.05, 0.86; P=0.039). Our human trial has transitioned to Phase Ib which will further evaluate the safety and potential benefits of PT-CY/BEN. Herein, we also expand our pediatric, adolescent, and young adult (AYA) experience to 31 patients demonstrating an overall survival (OS), progression-free survival (PFS) and GRFS at 3 years of 85.6%, 76.1% and 58.2%, respectively in a largely racial/ethnic minority cohort.
PT-CY/BEN appears to be a promising treatment option that requires further evaluation.

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