mycophenolic-acid and Kidney-Neoplasms

Immune checkpoint inhibition with the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab has improved survival in metastatic melanoma, lung cancer and renal cancer. Use of these agents holds promise in other malignancies. The augmented immune response enabled by these agents has led to a particular group of side effects called immune-related adverse events (irAEs). The main irAEs include diarrhea, colitis, hepatitis, skin toxicities and endocrinopathies such as hypophysitis and thyroid dysfunction. The anti-PD-1 antibodies have a different toxicity profile to ipilimumab with fewer high grade events. This article identifies the rates of common and uncommon irAEs associated with each immune checkpoint inhibitor (ICPI) and their timing of onset, focusing mainly on the experience in melanoma and lung cancer. An approach to management for each class of irAE is provided.

Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Antineoplastic Agents; Carcinoma, Renal Cell; Chemical and Drug Induced Liver Injury; Colitis; CTLA-4 Antigen; Cyclosporine; Diarrhea; Drug Eruptions; Humans; Immunosuppressive Agents; Infliximab; Ipilimumab; Kidney Neoplasms; Lung Neoplasms; Melanoma; Mycophenolic Acid; Neoplasms; Nivolumab; Pituitary Diseases; Programmed Cell Death 1 Receptor; Skin Neoplasms; Tacrolimus; Thyroiditis

Safety and efficacy of two sirolimus (SRL)-based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF). Renal transplantation recipients were randomized to Group 1 (SRL+TAC; week 13 TAC elimination [n = 152]), Group 2 (SRL + MMF [n = 152]) or Group 3 (TAC + MMF [n = 139]). Group 2, with higher-than-expected biopsy-confirmed acute rejections (BCARs), was sponsor-terminated; therefore, Group 2 two-year data were limited. At 1 and 2 years, respectively, graft (Group 1: 92.8%, 88.5%; Group 2: 90.6%, 89.9%; Group 3: 96.2%, 95.4%) and patient (Group 1: 97.3%, 94.4%; Group 2: 95.2%, 94.5%; Group 3: 97.0%, 97.0%) survival rates were similar. One- and 2-year BCAR incidence was: Group 1, 15.2%, 17.4%; Group 2, 31.3%, 32.8%; Group 3, 8.2%, 12.3% (Group 2 vs. 3, p < 0.001). Mean 1- and 2-year modified intent-to-treat glomerular filtration rates (mL/min) were similar. Primary reason for discontinuation was adverse events (Group 1, 34.2%; Group 2, 33.6%; Group 3, 22.3%; p < 0.05). In Groups 1 and 2, delayed wound healing and hyperlipidemia were more frequent. One-year post hoc analysis of new-onset diabetes posttransplantation was greater in TAC recipients (Groups 1 and 3 vs. 2, 17% vs. 6%; p = 0.004). Between-group malignancy rates were similar. The SRL-based regimens were not associated with improved outcomes for kidney transplantation patients.

Topics: Adult; Female; Humans; Immunosuppressive Agents; Kidney Neoplasms; Male; Middle Aged; Mycophenolic Acid; Sirolimus; Tacrolimus

This phase I trial assessed the safety, efficacy, and immunologic responses to minor histocompatibility antigens following nonmyeloablative allogeneic hematopoietic cell transplantation as treatment for metastatic renal cell carcinoma.. Eight patients received conditioning with fludarabine and low-dose total body irradiation followed by hematopoietic cell transplantation from an HLA-matched sibling donor. Cyclosporine and mycophenolate mofetil were administered as posttransplant immunosuppression. Patients were monitored for donor engraftment of myeloid and lymphoid cells, for clinical response by serial imaging, and for immunologic response by in vitro isolation of donor-derived CD8(+) CTLs recognizing recipient minor histocompatibility (H) antigens.. All patients achieved initial mixed hematopoietic chimerism with two patients rejecting their graft and recovering host hematopoiesis. Four patients developed acute, grade 2 to 3, graft-versus-host disease and four patients developed extensive chronic graft-versus-host disease. Five patients had progressive disease, two patients had stable disease, and one patient experienced a partial response after receiving donor lymphocyte infusions and IFN-alpha. CD8(+) CTL clones recognizing minor H antigens were isolated from five patients studied. Clones from three patients with a partial response or stable disease recognized antigens expressed on renal cell carcinoma tumor cells.. Treatment of metastatic renal cell carcinoma with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning with fludarabine/total body irradiation is feasible and may induce tumor regression or stabilization in some patients. CD8(+) CTL-recognizing minor H antigens on tumor cells can be isolated posttransplant and could contribute to the graft-versus-tumor effect. Such antigens may represent therapeutic targets for posttransplant vaccination or adoptive T-cell therapy to augment the antitumor effects of allogeneic hematopoietic cell transplantation.

Topics: Adenocarcinoma, Clear Cell; Adult; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Papillary; Carcinoma, Renal Cell; Cells, Cultured; Cyclosporine; Female; Graft vs Host Disease; Graft vs Tumor Effect; Hematopoietic Stem Cell Transplantation; Humans; Kidney Neoplasms; Male; Middle Aged; Minor Histocompatibility Antigens; Mycophenolic Acid; Myeloid Cells; T-Lymphocytes, Cytotoxic; Tissue Donors; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Whole-Body Irradiation

This study aims to identify modifiable risk factors for de novo renal cell carcinoma (RCC) after kidney transplantation in a matched-pair approach matching for unmodifiable factors.. One thousand six hundred fifty-five adults who underwent kidney transplantation in the period 1 January 2000 to 31 December 2012 were analyzed. Patients with RCC after kidney transplantation were matched in a 1:2 ratio with those without RCC using the indication for transplantation, age at transplantation (± 10 years), recipient sex (male/female), number of received transplants, living organ donor transplantation (yes/no), and time of follow-up in days as matching criteria. The paired t test was used to compare continuous variables and the Cochran-Mantel-Haenszel test for categorical variables. Multivariable conditional logistic regression modeling was used to identify independent risk factors for RCC.. In matched-pair analysis, a total number of 26 incident cases with RCC after kidney transplantation could be matched. Post-transplant RCC was significantly associated with longer durations of pre-transplant hemodialysis (p = 0.007) and post-transplant immunosuppression with cyclosporine (p = 0.029) and/or mycophenolate mofetil (p = 0.020) and with larger proportions of post-transplant time on mycophenolate mofetil (p = 0.046) and/or prednisolone medication (p = 0.042). Multivariable conditional logistic regression modeling revealed a significant risk increasing multiplicative factor interaction between the duration of pre-transplant dialysis (years) and the time of prednisolone usage (percent/100). Cyclosporine A usage and mycophenolate mofetil usage were also revealed as independent, significant risk factors for RCC development.. Longer pre-transplant dialysis, cyclosporine-based protocols and/or intensified immunosuppression with additional mycophenolate mofetil, and larger proportions of time of prednisolone treatment during follow-up increase de novo RCC risk.

Topics: Adult; Aged; Carcinoma, Renal Cell; Cyclosporine; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Transplantation; Male; Matched-Pair Analysis; Middle Aged; Mycophenolic Acid; Prednisolone; Renal Dialysis; Retrospective Studies; Risk Factors; Time Factors; Young Adult

Topics: Adrenal Cortex Hormones; Adult; Atrophy; Biomarkers, Tumor; Carcinoma, Renal Cell; Glomerulonephritis, Membranous; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney; Kidney Diseases, Cystic; Kidney Neoplasms; Kidney Transplantation; Male; Mucin-1; Mycophenolic Acid; Nephrectomy; Postoperative Complications; Reoperation; Tacrolimus

Topics: Female; Humans; Immunosuppressive Agents; Kidney Neoplasms; Male; Mycophenolic Acid; Sirolimus; Tacrolimus

A 53-year-old man who underwent successful kidney transplantation for stage 5 chronic kidney disease presented to our clinic with intermittent painless gross hematuria. Urachal adenocarcinoma, stage III A by Sheldon system, was diagnosed after serial histopathologic and radiological studies. The patient was treated with extended partial cystectomy, en bloc resection of urachus and umbilicus, pelvic lymphadenectomy, and ileocystoplasty. There were no complications seen in this patient. Neither urachal adenocarcinoma recurrence, metastasis, nor de novo uroileal cancer developed during 48-month follow-up. His reconstructed bladder functioned efficiently, without compromising the transplanted kidney function. Our case demonstrated that conservative surgery and augmentation ileocystoplasty could be offered to kidney transplant recipients with localized urachal carcinoma.

Topics: Adenocarcinoma; Hematuria; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Neoplasms; Kidney Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Mycophenolic Acid; Neoplasm Staging; Prednisolone; Tacrolimus; Urachus

We describe a case of chronic mineralizing pulmonary elastosis in a seven-yr-old boy following DD renal transplantation for Wilms tumour. Fourteen months post-transplantation he developed respiratory symptoms with lung biopsy demonstrating chronic mineralizing pulmonary elastosis thought to be secondary to immunosuppression with MMF. Symptomatic resolution occurred following MMF cessation.

Topics: Calcinosis; Chronic Disease; Humans; Immunosuppressive Agents; Infant; Kidney; Kidney Neoplasms; Kidney Transplantation; Male; Mycophenolic Acid; Nephrectomy; Pulmonary Fibrosis; Remission Induction; Renal Dialysis; Tomography, X-Ray Computed; Wilms Tumor

Topics: Antilymphocyte Serum; Brain Neoplasms; Cytomegalovirus Retinitis; Epstein-Barr Virus Infections; Female; Ganciclovir; Graft Rejection; Herpesvirus 4, Human; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Neoplasms; Kidney Transplantation; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Muromonab-CD3; Mycophenolic Acid; Postoperative Complications; Prednisolone; Radiography; RNA, Viral; Tacrolimus; Transplantation, Homologous