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Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus
B Mookerjee1, V Altomonte, G Vogelsang
1The Bone Marrow Transplant Program, Johns Hopkins Oncology Center, Baltimore, MD, USA.
Insights
Refractory chronic graft-versus-host disease (GVHD) after bone marrow transplantation (BMT) showed a 46% response rate with a steroid-sparing mycophenolate mofetil and tacrolimus combination. This regimen was well-tolerated and warrants further investigation for improved survival and quality of life.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Chronic graft-versus-host disease (GVHD) is a significant complication following allogeneic bone marrow transplantation (BMT), leading to substantial morbidity and non-relapse mortality.
- Despite advances in managing acute GVHD, chronic GVHD rates remain a concern due to factors like an aging patient population, increased use of mismatched and unrelated donors, and donor lymphocyte infusions for relapsed disease.
- Patients with high-risk chronic GVHD or those refractory to standard treatments face a poor prognosis, with limited success from current salvage therapies.
Purpose of the Study:
- To evaluate the efficacy and tolerability of a steroid-sparing combination of mycophenolate mofetil (MMF) and tacrolimus in patients with refractory chronic GVHD.
- To assess the potential of this synergistic regimen to improve outcomes, including survival and quality of life, in a challenging patient population.
Main Methods:
- A retrospective analysis was conducted on 26 patients diagnosed with refractory chronic GVHD.
- The treatment regimen involved a combination of mycophenolate mofetil (MMF) and tacrolimus, specifically designed to spare the use of steroids.
- Patient responses were categorized into objective response, stable disease, progression, and not evaluable.
Main Results:
- An objective response rate of 46% was observed in patients treated with the MMF and tacrolimus combination.
- An additional 11.5% of patients achieved stable disease, while 34.6% experienced disease progression.
- The combination therapy was generally well-tolerated by the study participants, suggesting a favorable safety profile.
Conclusions:
- The steroid-sparing combination of mycophenolate mofetil (MMF) and tacrolimus demonstrated promising preliminary results in treating refractory chronic GVHD.
- These findings support the initiation of a prospective trial to further assess the safety and efficacy of this regimen, aiming to improve survival and quality of life in patients with chronic GVHD who have failed prior therapies.
Abstract:
Chronic graft-versus-host disease (GVHD) is a common late complication of allogeneic bone marrow transplantation (BMT) and is the principal cause of morbidity and non-relapse mortality. The improved management of acute GVHD has not translated into lower rates of chronic GVHD as older patients undergo allogeneic BMT, more patients receive unrelated or related mismatched allogeneic BMT, and donor lymphocyte infusion is increasingly used for treatment of post-BMT relapses. Patients with high risk chronic GVHD or those who fail on standard therapy have a bad prognosis. Salvage therapies have produced disappointing results. Here, we present a retrospective analysis of 26 patients where a steroid sparing synergistic combination of mycophenolate mofetil (MMF) and tacrolimus was used in refractory chronic GVHD. 46% patients showed an objective response, 11.5% had stable disease, 34.6% had progression and 7.7% were not evaluable. The combination was well tolerated. This promising preliminary result has prompted a trial to assess the safety and efficacy of this regimen in patients with chronic GVHD who have failed prior therapy and to determine if it would improve survival as well as quality of life in such patients.