A prospective single-center study on CNI-free GVHD prophylaxis with everolimus plus mycophenolate mofetil in allogeneic HCT.

Abstract

We report a single-center phase I/II trial exploring the combination of everolimus (EVE) and mycophenolate mofetil (MMF) as calcineurin inhibitor (CNI)-free GVHD prophylaxis for 24 patients with hematologic malignancies and indication for allogeneic HCT after a high dose or reduced-intensity ablative conditioning. The study was registered as EudraCT-2007-001892-12 and Clinicaltrials.gov as NCT00856505. All patients received PBSC grafts and no graft failure occurred. 7/24 patients (29%) developed acute grades III and IV GVHD (aGVHD), 16/19 evaluable patients (84%) developed chronic GVHD (cGVHD) of all grades, and 6/19 (31.6%) of higher grades. No severe toxicities related to study medication were observed. The median follow-up of all surviving patients is 2177 days. The 3-year OS was 45.2% (95% CI: 27.4-61.4%), and the 3-year PFS was 38.7% (95% CI: 22.0-55.1%). The cumulative incidence of relapse at 1 year and 3 year was 25% (95% CI: 12.5-50.0%), and 33.3% (95% CI: 18.9-58.7%), the cumulative incidence of NRM at 1 year and 3 years was 20.8% (95%CI: 9.6-45.5%), and 29.2% (95%CI: 15.6-54.4%), respectively. The utilization of CNI-free GVHD prophylaxis with EVE+MMF resulted in high rates of acute and chronic GVHD. Therefore, we do not recommend a CNI-free combination of mTOR inhibitor EVE with MMF as the sole GVHD prophylaxis. In subsequent studies, this combination should be modified, e.g., with further components like post-transplant cyclophosphamide (PTCy) or anti-thymocyte globulin (ATG).

• Authors: Henning Schäfer, Jacqueline Blümel-Lehmann, Gabriele Ihorst, Hartmut Bertz, Ralph Wäsch, Robert Zeiser, Jürgen Finke, Reinhard Marks
• Journal: Annals of hematology (Ann Hematol) Vol. 100 Issue 8 Pg. 2095-2103 (Aug 2021) ISSN: 1432-0584 [Electronic] Germany
• PMID: 33755792 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Antibiotics, Antineoplastic
• Immunosuppressive Agents
• Everolimus
• Mycophenolic Acid

Topics

• Adult
• Aged
• Antibiotics, Antineoplastic (therapeutic use)
• Everolimus (therapeutic use)
• Graft vs Host Disease (etiology, prevention & control)
• Hematologic Neoplasms (therapy)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Male
• Middle Aged
• Mycophenolic Acid (therapeutic use)
• Prospective Studies
• Transplantation, Homologous (adverse effects, methods)
• Young Adult