mycophenolic-acid and Lung-Neoplasms

Immune checkpoint inhibitors (ICIs) sometimes cause immune-related liver injury, which can lead to cessation of treatment, hospitalization, and even mortality. Although high-dose corticosteroids are usually effective in treatment of ICI-related liver injury, one fifth of affected patients require additional immunosuppressive therapy. It remains uncertain how best to treat ICI-related liver injury that relapses under corticosteroid therapy after temporary remission.. Here we report two cases of ICI-related liver injury successfully treated with mycophenolate mofetil (MMF). In the first case, a 74-year-old man with stage IIIA lung cancer underwent curative chemoradiotherapy. After the second infusion of durvalumab, grade 3 ICI-related liver injury (mixed pattern) developed. In the second case, a 46-year-old man with stage IVB lung cancer received pembrolizumab-containing chemotherapy. After the first cycle, grade 2 ICI-related hepatitis developed. In the both cases, liver injury improved with high-dose prednisolone but relapsed during tapering of the drug. After liver biopsy was performed to confirm the diagnosis of ICI-related liver injury, MMF (2000 mg/day) was added. MMF was effective for both patients and permitted discontinuation or reduction of prednisolone.. MMF appears to be an appropriate treatment option for ICI-related liver injury that respond to high-dose corticosteroids but relapse during steroid tapering.

Topics: Adrenal Cortex Hormones; Aged; Chemical and Drug Induced Liver Injury; Drug Tapering; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Male; Middle Aged; Mycophenolic Acid; Neoplasm Recurrence, Local; Prednisolone

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

The emergence of immune checkpoint inhibitors (ICIs) has significantly prolonged the survival time of cancer patients. However, it may also lead to various immune-related adverse events (irAEs), including Guillain-Barré syndrome (GBS), a rare type of irAE. Most GBS patients can recover spontaneously due to the self-limited nature of the disease, but severe cases can result in respiratory failure or even death. Here we report a rare case of GBS occurring in a 58-year-old male patient with non-small cell lung cancer (NSCLC) who developed muscle weakness and numbness of the extremities during chemotherapy combined with KN046, a PD-L1/CTLA-4 bispecific antibody. Despite receiving methylprednisolone and γ-globulin, the patient's symptoms did not improve. However, there was significant improvement after treatment with mycophenolate mofetil (MM) capsules, which is not a routine regimen for GBS. To the best of our knowledge, this is the first reported case of ICIs-induced GBS that responded well to mycophenolate mofetil instead of methylprednisolone or γ-globulin. Thus, it provides a new treatment option for patients with ICIs-induced GBS.

Topics: Antibodies, Bispecific; Carcinoma, Non-Small-Cell Lung; Guillain-Barre Syndrome; Humans; Lung Neoplasms; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid

A 69-year-old man with stage III lung squamous cell carcinoma developed immune-related hepatitis following treatment with durvalumab, and was given high-dose corticosteroids and immunosuppressive drugs (mycophenolate mofetil, azathioprine, tacrolimus) but without demonstrating any improvement. Two cycles of infliximab (5 mg/kg) were then administered and thereafter the hepatitis improved. At the time of writing (9 months after the initiation of first course of durvalumab), the patient is alive without either any hepatitis symptoms nor any lung cancer progression. Infliximab may be effective for treating non-small cell lung cancer (NSCLC) patients who develop immunosuppressive drug-resistant immune-related hepatitis caused by durvalumab.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Azathioprine; Carcinoma, Non-Small-Cell Lung; Chemical and Drug Induced Liver Injury; Humans; Immunosuppressive Agents; Infliximab; Lung Neoplasms; Male; Mycophenolic Acid

Pulmonary lymphangioleimyomatosis (PLAM) is a rare disease involving lung. PLAM primarily affects young women, a characteristic it shares with systemic lupus erythematosus (SLE). Estrogen has long been assumed to play an important role both in PLAM and SLE. We report a menopausal woman, who was found to have PLAM 1 year after she was diagnosed with SLE. Her chest radiograph was normal in the early phase of SLE.. A 52-year-old Chinese woman was referred to our hospital in August 2014 because of swelling in both legs. She also reported a malar rash and intermittent generalized arthralgia. Laboratory examination showed leukopenia. Her serum albumin level was 23 g/L; 24-h urinary protein excretion was 5.3 g. She tested positive for anti-Smith (Sm) antibody and anti-SS-A antibody. Renal biopsy indicated Class V + IV(G)-A lupus nephritis (LN). The condition of SLE and LN improved on a regime of tapering prednisolone and intermittent intravenous cyclophosphamide therapy until 1 year later when she developed exertional dyspnea accompanied with frequent cough. Thoracic computed tomography revealed numerous well-defined cysts and the diagnosis of PLAM was confirmed by lung biopsy. In the follow-up period, the patient continued to be on prednisolone and mycophenolate mofetil for the treatment of SLE, but only agreed to receive symptomatic treatment for PLAM. One year after the diagnosis of PLAM, during which time the SLE was stable, she died of respiratory failure and cor pulmonale.. We report a patient with coexisting SLE and PLAM, who was treated with immunosuppressive therapy. SLE was stable but PLAM was not improved. Although the coexistence of SLE and PLAM might be a coincidence, the occurrence of these two diseases in a menopausal woman may warrant further mechanistic exploration.

Topics: Anti-Bacterial Agents; Cyclophosphamide; Drug Therapy, Combination; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Leiomyomatosis; Lung Neoplasms; Lupus Nephritis; Lymphangioma; Menopause; Methylprednisolone; Middle Aged; Mycophenolic Acid; Pneumonia, Bacterial; Prednisolone

Topics: Adult; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antiviral Agents; Biopsy; Combined Modality Therapy; Disease Progression; Hepatitis C; Humans; Immunocompromised Host; Immunosuppressive Agents; Lip Neoplasms; Liver Function Tests; Liver Transplantation; Lung Neoplasms; Male; Melanoma; Mycophenolic Acid; Neoplasm Staging; Steroids

Topics: Administration, Oral; Aged; Antibodies, Monoclonal; Antineoplastic Agents; Dacarbazine; Drug Administration Schedule; Fluorodeoxyglucose F18; Humans; Immunosuppressive Agents; Ipilimumab; Kidney Transplantation; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Mycophenolic Acid; Platinum Compounds; Positron-Emission Tomography; Prednisone; Radiopharmaceuticals; Skin Neoplasms; Tacrolimus; Temozolomide; Tomography, X-Ray Computed; Treatment Outcome

Cancer after heart transplant is recognized as a leading cause of morbidity and mortality. A man's clinical course after receiving a heart transplant is described, with emphasis on important clinical considerations in the care of heart transplant recipients.

Topics: Azathioprine; Carcinoma, Squamous Cell; Drug Therapy, Combination; Fatal Outcome; Glucocorticoids; Heart Transplantation; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Neoplasms; Male; Mediastinal Neoplasms; Middle Aged; Mycophenolic Acid; Neoplasm Recurrence, Local; Pleural Neoplasms; Prednisone; Sirolimus; Skin Neoplasms; Tacrolimus

Topics: Amyotrophic Lateral Sclerosis; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Carcinoma, Small Cell; Disease Models, Animal; Humans; Immunologic Factors; Immunosuppressive Agents; Lambert-Eaton Myasthenic Syndrome; Lung Neoplasms; Mycophenolic Acid; Myelin-Associated Glycoprotein; Neuromuscular Diseases; Polyneuropathies; Rats; Rituximab; Superoxide Dismutase; Superoxide Dismutase-1

Everolimus inhibits the growth of several tumor cell lines in vitro as well as tumor growth in a rat model. Mycophenolate mofetil (MMF) inhibits growth of a Walker sarcoma in a rat model in vivo. Herein we tested the in vitro antiproliferative capacity of everolimus and MMF on a pancreatic tumor cell line Panc-1 and on a small cell lung cancer cell line ScLc.. Cells were cultured under standardized conditions. Everolimus was added in increasing doses from 0.005 to 500 microg/mL; MMF was used from 0.05 to 5000 microg/mL. For co-incubation experiments, we combined everolimus (0.005 microg/mL and 0.05 microg/mL) with five concentrations of MMF; and MMF (0.5 microg/mL and 5 microg/mL) with five concentrations of everolimus. The antiproliferative capacity was assessed by a BrdU incorporation assay.. Everolimus and MMF inhibited BrdU incorporation into Panc-1 and ScLc in a dose-dependent fashion. A 50% inhibition was seen in Panc-1 only at 50 microg/mL everolimus, but in ScLc at 5 microg/mL everolimus. MMF was clearly more potent in Panc-1: 50% inhibition was observed at 5 microg/L. In ScLc, 40% inhibition of BrdU incorporation was seen only at 50 microg/L MMF. In co-incubation, an effective combination for both Panc-1 and ScLc was 5 microg/mL MMF with 0.005 microg/mL everolimus resulting in 50% inhibition of BrdU incorporation (P < .001).. Everolimus and MMF showed dose-dependent antiproliferative effects in tumor cell lines in vitro both alone and in combination. The combined use of everolimus and MMF showed supra-additive effects at concentrations used for therapeutic immunosuppression in patients.

Topics: Animals; Carcinoma 256, Walker; Cell Division; Cell Line, Tumor; Everolimus; Immunosuppressive Agents; Lung Neoplasms; Mycophenolic Acid; Pancreatic Neoplasms; Rats; Sirolimus

Topics: Adult; Female; Humans; Immunosuppression Therapy; Liver Neoplasms; Liver Transplantation; Lung Neoplasms; Mycophenolic Acid; Neoplasm Metastasis; Sirolimus; Tomography Scanners, X-Ray Computed; White People

Kaposi's sarcoma (KS) is an human herpesvirus 8-associated tumor, occurring in immunocompromised patients. We report here an increased incidence of KS among kidney graft recipients (KGRs) during the last 2 years, concomitant to the introduction of the immunosuppressant mycophenolate mofetil (MMF).. A total of 1835 KGRs, receiving organs between 1987 and 1997, were surveyed for the development of KS. A total of 371 patients received therapy including MMF (group A), whereas 1464 patients were treated with an MMF-free protocol (group B).. 3/371 patients (0.8%) of group A versus 2/1464 patients (0.1%) of group B developed KS. In group A, KS became evident 7+/-2 months after initiation of MMF therapy.. At our center, during the last 2 years, the incidence of KS has increased in KGRs, and it is not clear whether the introduction of MMF contributes to the phenomenon.

Topics: Drug Therapy, Combination; Extremities; Fatal Outcome; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Lung Neoplasms; Male; Middle Aged; Mycophenolic Acid; Postoperative Care; Postoperative Complications; Radiography; Sarcoma, Kaposi; Skin Neoplasms