Faculty Collaboration Database

Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. J Clin Oncol 2022 Feb 01;40(4):356-368

Date

12/03/2021

Pubmed ID

34855460

Pubmed Central ID

PMC8797487

DOI

10.1200/JCO.21.02293

Scopus ID

2-s2.0-85123901255 (requires institutional sign-in at Scopus site)   68 Citations

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; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037).

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.

Author List

Luznik L, Pasquini MC, Logan B, Soiffer RJ, Wu J, Devine SM, Geller N, Giralt S, Heslop HE, Horowitz MM, Jones RJ, Litzow MR, Mendizabal A, Muffly L, Nemecek ER, O'Donnell L, O'Reilly RJ, Palencia R, Schetelig J, Shune L, Solomon SR, Vasu S, Ho VT, Perales MA

Authors

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Marcelo C. Pasquini MD, MS Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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