Novel Approaches to the Treatment of Chronic Graft-Versus-Host Disease

Abstract

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. Chronic graft-versus-host disease (cGVHD) is an immune-mediated disease that ensues after allogeneic hematopoietic cell transplantation often affecting multiple organs, decreases quality of life, and necessitates immunosuppressive therapy. The current standard first-line cGVHD therapy is glucocorticoids (GCs) which have major side effects. So far, all attempts to improve response to first-line GC therapy of cGVHD by adding other agents, such as mycophenolate mofetil, or cyclosporine A have not improved response. The data reported in the trial by Miklos et al indicate that ibrutinib should not be added to GC in first-line cGVHD therapy. The findings instruct future studies that aim at the identification of patients with cGVHD who may benefit from a GC-ibrutinib combination using biomarkers or clinical parameters. Currently, ibrutinib, ruxolitinib, and belumosudil are the only drugs that are approved by the Food and Drug Administration for steroid-refractory cGVHD. In light of the current standard management of cGVHD, the trial results indicate that ibrutinib will remain reserved for second-line therapy, which may be due to its mechanisms of action. The recommendation on the basis of this trial is that GC monotherapy remains the standard therapy for cGVHD.

Repeated Infusions of Bone-Marrow-Derived Mesenchymal Stem Cells over 8 Weeks for Steroid-Refractory Chronic Graft-versus-Host Disease: A Prospective, Phase I/II Clinical Study

“…Newly approved immunomodulatory agents, such as ibrutinib [ 9 ] and ruxolitinib [ 8 ], are currently being incorporated into second-line management strategies for chronic graft-versus-host disease (cGVHD) [ 46 ]. There is a lack of prospective and retrospective studies comparing MSC therapy with other immunosuppressants.…”

Phototherapie in Theorie und Praxis

“…In der aktuellen Leitlinie zur akuten GvHD finden die PUVA und die UVB-Therapie als Zweitli-nientherapien zur Behandlung der isolierten Haut-GvHD Eingang in die Empfehlungen. 86…”

Body Surface Area-Based Dosing of Mycophenolate Mofetil in Pediatric Hematopoietic Stem Cell Transplant Recipients: A Prospective Population Pharmacokinetic Study

“…All patients received oral MMF for the prophylaxis and treatment of aGVHD. The MMF dosage was administered at 15-20 mg/kg twice daily in either oral suspension or capsule formulation [10,13,37]. Whole blood samples were drawn at pre-dose at 0 h and at post-dose 1, 2, 6 h after MMF administration at least 3 days after the initiation of MMF to ensure that the MPA concentration had reached a steady-state concentration.…”

“…MMF is an immunosuppressant drug used with calcineurin inhibitors for prophylaxis and treatment of graft-versus-host disease (GVHD) after HSCT as off-label in pediatric and adult patients [9][10][11]. For adult HSCT patients, the recommended MMF dosage is determined to be administered at 10-15 mg/kg twice daily or 1 g twice daily [12,13]. Although dosing regimens for pediatric HSCT patients have been extrapolated from pediatric solid organ transplantation and adult HSCT pharmacokinetic studies [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], there is no standardized dosing regimen for pediatric HSCT recipients due to a lack of clinical evidence.…”