Mycophenolate mofetil for the treatment of acute and chronic steroid-refractory graft-versus-host disease

Abstract

Corticosteroid-resistant graft-versus-host disease (GvHD) is difficult to manage and is associated with high morbidity and mortality. The purpose of our study was to evaluate the safety and efficacy of mycophenolate mofetil (MMF) as the salvage therapy for steroid-refractory GvHD. Twenty one patients (10 with acute GvHD and 11 with chronic GvHD) were studied retrospectively. Steroid-resistant GvHD was defined as acute or chronic GvHD not responding to a first-line regimen of cyclosporine A and corticosteroids in a dose equivalent to 2 mg/kg methylprednisolone for at least 7 days. MMF was added at a dose of 2 g daily, and corticosteroids were tapered. Thirteen (62%) of 21 patients responded to the treatment with MMF, including 6 (60%) of 10 patients with acute refractory GvHD and 7 (64%) of 11 patients with chronic refractory GvHD. The most common adverse effects were infectious complications (67%, 14 of 21 patients) and hematological toxicity (29%, 6 of 21 patients). Median duration of MMF administration was 6 months (range 1-27 months). Sixteen of 21 patients were alive after the median follow-up of 27 months (range 1-72 months) after the initiation of MMF therapy. All 16 surviving patients were in good clinical condition and in remission of their hematological malignancy. Five patients died--two of relapses of leukemia and three of refractory intestinal GvHD. These results suggest that MMF can be an effective treatment for some cases of steroid-refractory GvHD.

UVA (UVA-1) therapy for the treatment of acute GVHD of the skin

“…In addition, durable responses to first-line steroids are only seen in 20-40% of patients. 8,11,12 For these reasons, there is a real need for the development of non-pharmacological approaches for the treatment of acute GVHD of the skin. Long-wavelength UVA (340-400 nm; UVA-1) therapy has been used in our department since 2002.…”

“…1,2,[8][9][10][11] A major side effect of systemic glucocorticoids is an increased risk of infection and of relapse of the underlying malignancy. 8,12 In addition, only 20-40% of patients show a durable response to first-line glucocorticoid treatment. 11 These results emphasize the need for new treatment options for acute GVHD.…”

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

“…[31][32][33][36][37][38] Direct comparisons to other series examining MMF in refractory GVHD are difficult for several reasons. Basara et al reported an overall grade improvement in 65% of patients, where MMF was used as first-line therapy in addition to CSA and prednisolone on development of aGVHD or cGHVD.…”

“…[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Mycophenolate mofetil (MMF), whose metabolite mycophenolic acid inhibits the de novo synthesis of purines in lymphocytes, has probable efficacy in the treatment of aGVHD, based on three small case series that cumulatively reported 17 cases in which MMF was used for initial therapy for aGVHD, and 16 cases with glucocorticoidrefractory aGVHD. [31][32][33] Here, we report outcomes in a series of 27 recipients of allogeneic hematopoietic cell transplantation treated with MMF as salvage therapy for steroid-refractory aGVHD.…”

Combination antithymocyte globulin and soluble TNFα inhibitor (etanercept) +/− mycophenolate mofetil for treatment of steroid refractory acute graft-versus-host disease

“…The first involves use of cytotoxic agents directed towards effector (T) cells, with agents such as antithymocyte globulin (ATG), OKT3 or mycophenolate mofetil (MMF). [2][3][4][5][6] The second approach is based upon blockage of cytokine pathways involved in the pathogenesis of acute GVHD, by use of antibodies inhibiting especially tumor necrosis factor-a (TNFa) (etanercept, infliximab) and interleukin-2 (dacluzimab, basiliximab) pathways. [7][8][9][10][11][12][13][14][15][16][17] We have previously reported on use of tacrolimus and ATG for steroid refractory acute GVHD.…”