| 2020 | A Phase 1 Study of IRX195183, a RARα-Selective CYP26 Resistant Retinoid, in Patients With Relapsed or Refractory AML. | Front Oncol | Subsets of non-acute promyelocytic leukemia (APL) acute myelogenous leukemia (AML) exhibit aberrant retinoid signaling and demonstrate sensitivity to retinoids . We present the results of a phase 1 dose-escalation study that evaluated the safety, pharmacodynamics, and efficacy of IRX195183, a novel retinoic acid receptor α agonist, in patients with relapsed or refractory myelodysplastic syndrome (MDS) or AML. In this single center, single arm study, eleven patients with relapsed or refractory MDS/AML were enrolled and treated. Oral IRX195183 was administered at two dose levels: 50 mg daily or 75 mg daily for a total of two 28-day cycles. Patients with stable disease or better were allowed to continue on the drug for four additional 28-day cycles. Common adverse events included hypertriglyceridemia, fatigue, dyspnea, and edema. Three patients at the first dose level developed asymptomatic Grade 3 hypertriglyceridemia. The maximally tolerated dose was not reached. Four of the eleven patients had (36%) stable disease or better. One had a morphological complete remission with incomplete hematologic recovery while on the study drug. Two patients had evidence of leukemic blast maturation, as reflected by increased CD38 expression. In a pharmacodynamics study, plasma samples from four patients treated at the lowest dose level demonstrated the capacity to differentiate leukemic cells from the NB4 cell line . These results suggest that IRX195183 is safe, achieves biologically meaningful plasma concentrations and may be efficacious in a subset of patients with MDS/AML. clinicaltrials.gov, identifier NCT02749708. |
| 2019 | Multiparameter Flow Cytometry for the Identification of Neoplastic Plasma Cells in POEMS Syndrome with IgG-kappa Gammopathy: Successful Treatment Using Lenalidomide and Dexamethasone. | Intern Med | A 72-year-old man presented with a 6-month history of systemic edema. Hyperpigmentation, hemangioma, pleural effusion, IgG-kappa-type monoclonal protein, high vascular endothelial growth factor values, renal failure, and nerve conduction study abnormalities were also present. Multiparameter flow cytometry (MFC) showed 0.2% neoplastic plasma cells (CD38-, CD56-, and kappa-positive; CD19-, CD27-, and lambda-negative) in the bone marrow leading to POEMS syndrome. Cases involving kappa-type POEMS syndrome are extremely rare. A kidney biopsy revealed membranous proliferative glomerulonephritis-like changes in our case. Lenalidomide-dexamethasone therapy improved the renal function. Detection of neoplastic plasma cells by MFC was useful for the accurate diagnosis and treatment evaluation. |
| 2017 | FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. | Oncologist | On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone. The estimated median PFS had not been reached in the daratumumab arm and was 18.4 months in the control arm (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.27-0.52; < .0001), representing a 63% reduction in the risk of disease progression or death. Similar results were observed in the MMY3004 trial comparing the combination of daratumumab, bortezomib, and dexamethasone with bortezomib and dexamethasone. The estimated median PFS was not reached in the daratumumab arm and was 7.2 months in the control arm (HR = 0.39; 95% CI: 0.28-0.53; < .0001), representing a 61% reduction in the risk of disease progression or death. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3003 were infusion reactions, diarrhea, nausea, fatigue, pyrexia, upper respiratory tract infection, muscle spasm, cough, and dyspnea. The most frequently reported adverse reactions (greater than or equal to 20%) in MMY3004 were infusion reactions, diarrhea, peripheral edema, upper respiratory tract infection, and peripheral sensory neuropathy. Neutropenia and thrombocytopenia have been added to the Warnings and Precautions of the drug label.Daratumumab, the first monoclonal antibody targeted against CD38, received U.S. Food and Drug Administration accelerated approval in 2015 based on data from single-agent, single-arm trials that provided response rate information. Results of the MMY3003 and MMY3004 trials established that daratumumab can be combined synergistically with some of the most highly active agents used to treat multiple myeloma, leading to daratumumab's regular approval in 2016. Daratumumab added to lenalidomide and dexamethasone, or bortezomib and dexamethasone, provides a substantial improvement in progression-free survival in previously treated patients with multiple myeloma. These combinations will likely improve the survival outlook for patients with multiple myeloma. |
| 2014 | The hysteroscopy and histological diagnosis and treatment value of chronic endometritis in recurrent implantation failure patients. | Arch Gynecol Obstet | To study the consistency of hysteroscopy findings and histological chronic endometritis (CE) in recurrent implantation failure (RIF) cases, and to compare their values in indicating antibiotic treatment.Sixty RIF cases (January 2009-January 2010) and 202 consecutive RIF cases (May 2010-April 2012) in Peking University Third Hospital reproductive medical center were studied. 60 RIF patients' endometrial samples redid section and CD38/CD138 immunohistochemical stain for CE screening. In 202 RIF cases, the presence of hyperemia, mucosal edema, and micropolyps under hysteroscopy were considered CE diagnostic parameters. Antibiotic was offered to part of the patients. The patients' clinical outcomes were analyzed by statistical methods.In 202 RIF cases, the hysteroscopy CE rate was 66.3 %, while histological CE rate was 43.6 %. The sensitivity and specificity of hysteroscopy were 35.2 and 67.5 %. In histological CE patients, 68 cases underwent regular antibiotic treatment and 20 did not. Two groups had similar clinical pregnancy rates (35.3 vs. 30.0 %), embryo implantation rates (18.9 vs. 20.4 %) and ongoing pregnancy rates (29.4 vs. 25.0 %). In hysteroscopy CE patients, the implantation rate (18.6 vs. 4.9 %) and ongoing pregnancy rate (29.3 vs. 7.4 %) significantly increased (P < 0.05) with antibiotic treatment, and higher intrauterine pregnancy rate in treatment group (29.3 vs. 11.1 %). In reviewing the chosen 60 RIF cases, the histological CE rates were similar in both pregnancy and non-pregnancy group after subsequent embryo transfer.CE occurs frequently in RIF patients; hysteroscopy has more diagnostic and treatment value for them. |
| 2007 | An anti-inflammatory effect of murine fetal liver cells in BALB/c mouse contact hypersensitivity model. | Int Immunopharmacol | Anti-inflammatory effects of murine fetal liver (FL) cells were studied using BALB/c mouse contact hypersensitivity (paw edema) model. Paw weight differences, lymphatic organ weights, hematological and histological indices as well as proinflammatory (TNF-alpha) and anti-inflammatory (IL-10) cytokine levels in sera were evaluated. Immunophenotyping revealed that both murine FL homogenate cells (HC) and FL hematopoietic stem cells (HSC) express CD117 and CD38 surface markers. Single doses of 1x10(6) cells/mouse and 2x10(6) cells/mouse of FL HC as well as of FL HSC, when used separately, all statistically significantly (p<0.05) inhibited paw edema, but the lower dose was more effective and giving results similar to that of prednisolone. Either dose of FL HC or FL HSC studied had no significant influence on lymphatic organ weights; no significant changes were also observed in blood indices. The data of cytokine studies showed that TNF-alpha concentration in sera of mice treated with either FL HC or FL HSC at a dose of 1x10(6) cells/mouse was statistically significantly (p<0.001) lower than that of the control mice. A concentration of IL-10 was statistically significantly higher (p<0.01) in mice treated with a dose of 1x10(6) cells/mouse of FL HC but not with the same dose of FL HSC as compared to the control group. Histological examination revealed better effects of a dose of 1x10(6) cells/mouse of FL HC when compared with the same dose of FL HSC as in regard to reduction of edema thickness and cell infiltration. |
| 1990 | Infiltrating leukocyte populations and T-lymphocyte subsets in head and neck squamous cell carcinomas from patients receiving perilymphatic injections of recombinant interleukin 2. A pathologic and immunophenotypic study. | Mod Pathol | Nine patients with squamous cell carcinoma of the oral cavity and oropharynx underwent preoperative perilymphatic administration of recombinant interleukin 2 (rIL-2). A more marked eosinophil and lymphocyte infiltration and more extensive edema than in 13 untreated cases were observed in surgical specimens. Necrosis was present in five of nine cases, but involved no more than 10% of the neoplastic tissue; in three of nine cases, characteristic necrotic changes with intense eosinophil infiltration possibly induced by lymphokines involved the peritumoral soft tissues. Of the tumor-infiltrating lymphocytes, T-lymphocytes (mostly CD4+ cells) prevailed over B-lymphocytes. CD4+ and CD8+ cells were mainly located close to the neoplastic sheets. Moderate amounts of CD38+ and CD11c+ cells (macrophages) and few CD16+ and CD56+ lymphocytes were found in all cases. CD25+ and LAK1+ cells were significantly more numerous in treated than in untreated cases. This suggests that local administration of rIL-2 induces an increase in activated T-lymphocyte subsets infiltrating the neoplastic tissue, thus eliciting a tumor-specific T-lymphocyte reactivity. |