Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies

Authors

Leo Luznik
Marcelo C Pasquini
Brent Logan
Robert J Soiffer
Juan Wu
Steven M Devine
Nancy Geller
Sergio Giralt
Helen E Heslop
Mary M Horowitz
Richard J Jones
Mark R Litzow
Adam Mendizabal
Lori Muffly
Eneida R Nemecek
Lynn O'Donnell
Richard J O'Reilly
Raquel Palencia
Johannes Schetelig
Leyla Shune
Scott R Solomon
Sumithira Vasu
Vincent T Ho
Miguel-Angel Perales

Publication Date

2-1-2022

Journal

Journal of Clinical Oncology

DOI

10.1200/JCO.21.02293

PMID

34855460

PMCID

PMC8797487

PubMedCentral® Posted Date

12-2-2021

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Adolescent, Adult, Aged, Calcineurin Inhibitors, Chronic Disease, Cyclophosphamide, Disease-Free Survival, Drug Therapy, Combination, Female, Germany, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Immunosuppressive Agents, Male, Methotrexate, Middle Aged, Myeloablative Agonists, Recurrence, Tacrolimus, Time Factors, Transplantation Conditioning, United States, Young Adult

Abstract

PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).

METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS).

RESULTS: Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15;

CONCLUSION: CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

Comments

Associated Data