Calcineurin Inhibitor–Free Chronic Graft-vs-Host Disease Interventions in Myeloablative HCT for Hematologic Malignancies

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As reported in the Journal of Clinical Oncology by Luznik et al, the phase III Blood and Marrow Transplant Clinical Trial Network 1301 trial has shown no improvement in the composite outcome of chronic graft-vs-host disease or relapse-free survival with calcineurin inhibitor–free regimens in patients undergoing myeloablative hematopoietic cell transplantation (HCT) for hematologic malignancies.

Study Details

In the open-label trial, 346 patients with acute leukemia or myelodysplasia and a human leukocyte antigen–matched donor from sites in the United States and Germany were randomly assigned 1:1:1 between September 2015 and June 2018 to receive: 

  • CD34-selected peripheral blood stem cell graft (n = 114)
  • Posttransplantation cyclophosphamide after bone marrow graft (n = 114)
  • The calcineurin inhibitor tacrolimus plus methotrexate after bone marrow graft (control group; n = 118).

The composite primary endpoint consisted of moderate or severe chronic graft-vs-host disease or relapse-free survival in the intent-to-treat population. For pairwise comparisons of outcomes, a P value of ≤ .017 was considered significant.

Key Findings

Rates of relapse-free survival at 2 years were 50.6% in the CD34 selection group (hazard ratio [HR] vs control group = 0.80, 95% confidence interval [CI] = 0.56–1.15, P = .24), 48.1% in the posttransplantation cyclophosphamide group (HR vs control = 0.86, 95% CI = 0.61–1.23, P = .41), and 41.0% in the control group.

Overall survival at 2 years was 60.1% in the CD34 selection group (HR vs control = 1.74, 95% CI = 1.09–2.80, P = .02), 76.2% in the posttransplantation cyclophosphamide group (HR vs control = 1.02, 95% CI = 0.60–1.72, P = .95), and 76.1% in the control group.

The CD34 selection group had lower 2-year rates of moderate to severe chronic graft-vs-host disease vs the control group (8.9% vs 33.7%, HR = 0.25, 95% CI = 0.12–0.52, P = .02) but higher transplant-related mortality (21.5% vs 7.9%, HR = 2.76, 95% CI = 1.26–6.06, P = .01). No significant difference in 2-year relapse rates was observed.

The posttransplantation cyclophosphamide group did not differ significantly vs the control group in 2-year rates of chronic graft-vs-host disease (27%; HR = 0.79, 95% CI = 0.48–1.29, P = .34) or transplant-related mortality (15.7%, HR = 1.88, 95% CI = 0.84–4.21, P = .13), but exhibited a trend towards lower 2-year relapse rate (13.9% vs 25.6%, HR = 0.52, 95% CI = 0.28–0.96, P = .037).

The investigators concluded, “Calcineurin inhibitor–free interventions as performed herein did not result in superior relapse-free survival compared with tacrolimus and methotrexate with bone marrow grafts. Lower rates of moderate and severe chronic [graft-vs-host disease] did not translate into improved survival.”

Marcelo C. Pasquini, MD, MS, of the Medical College of Wisconsin, Milwaukee, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by grants from the National Heart, Lung, and Blood Institute and National Cancer Institute and by Miltenyi Biotec. For full disclosures of the study authors, visit

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