Posttransplant Triplet Regimen as GVHD Prophylaxis for Myeloablative Allogeneic HSCT

By Dustin Samples - Last Updated: December 11, 2022

A new phase II study conducted at the University of Minnesota has demonstrated positive outcomes using a 3-drug combination for graft-versus-host disease (GVHD) prophylaxis after hematopoietic stem cell transplantation (HSCT). The results were presented at the 64th American Society of Hematology Annual Meeting and Exposition.

Myeloablative conditioning (MAC) with either matched related (MRD) or matched unrelated (MUD) donor allogeneic HCT is the current standard of care for younger patients with hematopoietic malignancies. Typically carried out using total body irradiation (TBI), MAC prepares the recipient (host) to receive the donor cells by suppressing the host’s immune system response. After transplantation, immunosuppressive therapy is required to prevent GVHD.

“An ideal HCT is one that combines strategies to reduce the incidence and severity of GVHD without compromising graft-versus-tumor effect,” lead author Alex Hoover, MD, wrote.

Dr. Hoover and his team hypothesized that a combination of posttransplant cyclophosphamide (PTCy), tacrolimus (TAC), and mycophenolate mofetil (MMF) would successfully prevent GVHD without increased risk of relapse in patients receiving MAC HCT.

This study enrolled 125 patients with a median age at transplant of 38 years. Most patients received MAC with TBI (89.6%); the remainder received MAC with busulfan and fludarabine.

The HCT source was 8/8 MRD for 69 patients (55.2%), 8/8 MUD for 44 (35.2%), and 7/8 MUD for 12 (9.6%).

By Day 42, all but 1 patient had achieved primary neutrophil engraftment, and by 6 months, 119 had achieved platelet engraftment.

Grade II-IV GVHD occurred in 16% of patients by Day 100, and grade III-IV GVHD occurred in only 4% by the same point.

“No patients experienced grade IV GVHD, and there were no deaths due to GVHD,” the study reported.

At 2 years posttransplant, relapse had occurred in 25%, and overall survival was 80%. Two-year GVHD-free, relapse-free survival was 57%.

The primary outcome of interest in this study was incidence of chronic GVHD, and it appears that the combination of MAC with either TBI or busulfan/fludarabine and GVHD prophylaxis with PTCy, TAC, and MMF was successful at preventing chronic GVHD.

“Further improvement in outcomes could potentially be achieved by incorporating posttransplant relapse mitigating strategies as well as supportive care measures to decrease regimen-related toxicities,” the researchers concluded.

Hoover A, O’Leary D, Cao Q, et al. Phase II study of myeloablative 8/8- or 7/8-matched allotransplantation with post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil: marked reduction in Gvhd risk without increased relapse risk compared to historical cyclosporine/methotrexate. Abstract #114. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.

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