Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

血管新生が進行性腎細胞癌の遠隔成績に及ぼす影響

著者らの施設において腎細胞癌の診断で腎摘除を行った148例中32例を対象に, 進行性腎細胞癌における血管新生因子, および治療に奏功した症例と進行した症例の相違について検討した.その結果, 1年, 5年そして10年生存率は各々82.4%, 30%, 30%であった.奏功症例(group A)は計4例で肺転移は3例に認められ, 2例に著効そして1例が有効であった.骨転移1例は有効であった.13例には奏功所見は認められなかった(group B).Thymidine Phosphorylaseはgroup Aがgroup Bより陽性率が高く, また多変量解析の結果, positive mean vascular areaが進行腎細胞癌における遠隔成績に影響をおよぼす独立した因子であることが示されたWe studied the relationship between angiogenic factors and clinical responses in advanced renal cell carcinomas (RCCs) and evaluated the angiogenic factors to clarify the potential impact of these factors on the cancer-specific survival. From January 1990 to December 2000, 148 patients underwent a nephrectomy for RCCs at our institution. Of the 32 patients who had distant metastasis, 17 met the histopathologic analysis requirements for an immuno-histochemical investigation. Fifteen of them were administered interferon-gamma and the remaining two patients were added to interferon-alpha and eight of seventeen patients also underwent radiation therapy. Both thymidine phosphorylase (TP) and Factor VIII immunostaining were performed. The overall survival rates at 1, 5 and 10 years were 82.4%, 30% and 30%, respectively. Three of these patients were diagnosed with lung metastasis and a complete response was seen in two, while a partial response was observed in one. In addition another patient who was diagnosed with bone metastasis also showed a partial response (group A). The remaining 13 patients showed progressive disease (group B). Group A had a higher TP-positive ratio (TP-PR) than that of group B. A multivariate analysis of the clinicopathologic data showed that a positive mean vascular area (PMVA) could be an independent factor regarding the potential impact of these factors on a long survival in advanced RCCS. PMVA was thus found to be an independent factor regarding the prognosis with advanced RCCs

Nimotuzumab enhances temozolomide-induced growth suppression of glioma cells expressing mutant EGFR in vivo

exterior, hous

インターフェロンγの腎細胞癌術後再発予防の長期成績 : 末梢血リンパ球は術後再発の指標となりえるか

This study examined the outcome of postoperative recurrence therapy on renal cell carcinoma (RCC) prevention involving treatment with single doses of interferon-gamma (IFN-gamma). From 1990-2000, 37 patients with no distant metastasis at the time they underwent a nephrectomy were enrolled in this investigation. Subcutaneous IFN-gamma was administered once a week. Total and differential white blood cells were counted before the pre-administration of IFN-gamma and then monthly thereafter for all patients. Blood lymphocyte subsets were analyzed phenotypically by direct immunofluorescence. Disease-free survival rates (DFSR) at 5 and 10 years were 81.7% and 75.9%, respectively. To clarify the effects of preoperative peripheral blood lymphocyte (PBL) and NK activity on DFSR, we categorized the patients into two groups according to the median number of PBL before the administration of IFN-gamma. Except for CD11b, PBL level had no effect on DFSR. Multiple logistic regression analysis showed that CD11b levels greater than 16.5% were associated with 25.35 odds ratio increase in the risk of postoperative recurrence. A multivariate analysis found that CD11b may be an independent factor for postoperative recurrence. In terms of preventing postoperative recurrence, our results showed that an elevated CD11b level may indicate patients who can benefit from further combination therapy.[目的]腎細胞癌術後再発に対するインターフェロンγの単剤投与の有用性について検討した.[対象と方法]1990～2000年までの間に原発巣摘除時に転移病巣のない腎細胞癌37例を対象とした.インターフェロンγを毎週連続で皮下投与して末梢血のリンパ球の分画について, 投与前, 投与後各1ヵ月ごとにflow cytometryを用いて検討した.[結果]37例中7例に再発が認められ, 非再発率は5年が81.7%, 10年が75.9%であった.術後再発に関わる影響を調べるため末梢血リンパ球とNK活性について投与前の中央値でおのおの2群に分けた.CD11bとNK活性を除いて術後再発に関連は認められなかった.多変量解析の結果, 投与前CD11bが16.5%以上だと16.5%未満の症例に比較して25.35倍術後再発が高く, 逆に投与前NK活性が13%以上の症例は0.25倍術後再発が減少する.[結語]多変量解析の結果術後に補助療法としてインターフェロンγ投与した症例では, CD11bとNK活性が術後再発に関わる独立した因子であることが判明した.また腎細胞癌の術後再発予防という観点からCD11bが高く, NK活性が低い症例には, さらなるcombination therapyが必要と考えられる(著者抄録

Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study

Oligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing