It has been reported that arsenic trioxide (ATO) regulates lymphoma cell cycle, apoptosis, autophagy and mitochondrial activity, while it synergizes with other cytotoxic agents. In addition, ATO targets anaplastic lymphoma kinase (ALK)-fusion oncoprotein to repress anaplastic large cell lymphoma (ALCL). The current study aimed to investigate the efficacy and safety of ATO plus etoposide, solumedrol, high-dose cytarabine and cisplatin (ESHAP) chemotherapy compared with ESHAP chemotherapy alone in patients with relapsed or refractory (R/R) ALK+ ALCL. A total of 24 patients with R/R ALK+ ALCL were enrolled in the present study. Among them, 11 patients were treated with ATO plus ESHAP, while the remaining 13 patients received ESHAP chemotherapy alone. Subsequently, treatment response, event-free survival (EFS), overall survival (OS) and adverse event (AEs) rates were recorded. Both complete response (72.7% vs. 53.8%; P=0.423) and objective response (81.8% vs. 69.2%; P=0.649) rates were higher in the ATO plus ESHAP group compared with the ESHAP group. However, statistical significance was not reached. In addition, EFS was significantly prolonged (P=0.047), while OS was not significantly increased (P=0.261) in the ATO plus ESHAP group compared with the ESHAP group. More specifically, the 3-year accumulating EFS and OS rates were 59.7 and 77.1% in the ATO plus ESHAP group, respectively, and 13.8 and 59.8% in the ESHAP group, respectively. The majority of AEs, such as thrombocytopenia (81.8% vs. 46.2%; P=0.105), fever (81.8% vs. 46.2%; P=0.105) and dyspnea (36.4% vs. 15.4%; P=0.182), were more prevalent in the ATO plus ESHAP group compared with the ESHAP group. However, no statistical significance was observed. In conclusion, the current study indicated that ATO plus ESHAP chemotherapy could exert a superior efficacy compared with ESHAP chemotherapy alone in patients with R/R ALK+ ALCL.

The mutation rate of anaplastic lymphoma kinase (ALK) in patients with non-small cell lung cancer is 3% to 7%. Due to its low mutation rate and better long-term survival compared with epidermal growth factor receptor-positive non-small cell lung cancer patients, therefore, it\'s called \"diamond mutation\". At present, there are three generations of ALK tyrosine kinase inhibitor (TKI) drugs in the world. The first-generation ALK-TKI drug approved in China is crizotinib, and the second-generation drugs are alectinib, ceritinib and ensartinib. Among them, ensartinib is an ALK-TKI domestically developed, and its efficacy is similar to that of alectinib. The main adverse event is transient rash, and compliance to ensartinib is better from the perspective of long-term survival of patients. The manifestation of rash caused by ensartinib is different from that of other ALK-TKI drugs. In order to facilitate clinical application and provide patients with more treatment options, under the guidance of the Committee of Cancer Rehabilitation and Palliative Care of China Anti-Cancer Association, this article collects and summarizes the common adverse reactions of ensartinib. Based on the clinical practice, a clear adverse classification and specific treatment plan are formulated, in order to provide a corresponding reference for clinicians to make more comprehensive clinical decisions.
非小细胞肺癌患者间变性淋巴瘤激酶(ALK)突变率为3%~7%。与表皮生长因子受体阳性非小细胞肺癌患者比较，ALK突变非小细胞肺癌患者更易获得长期生存，因此，ALK突变被称为钻石突变。目前，在全球范围内，ALK-酪氨酸激酶抑制剂(TKI)药物已经有三代药物。中国已获批的ALK-TKI第一代药物为克唑替尼，第二代药物为阿来替尼、塞瑞替尼和恩沙替尼。恩沙替尼为中国自主原研的ALK-TKI，其疗效与阿来替尼相似，耐受性表现为一过性皮疹，从患者长期生存的角度而言，顺应性更好。恩沙替尼引起的皮疹表现与其他ALK-TKI药物不同，为了便于临床应用和为患者提供更多的治疗选择，在中国抗癌协会肿瘤康复与姑息治疗专业委员会的指导下，专家收集汇总了恩沙替尼常见的不良反应，并结合临床实践制定了明确的不良分级及具体处理方案，以期为临床医师提供相应的参考依据。.

Aims: To describe the real-world economic burden of patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) treated with post-crizotinib, second-line ALK inhibitor therapy.Materials and methods: Retrospective analysis using data from US Optum: Clinformatics Data Mart administrative claims database. Adult patients with ALK + NSCLC treated with ceritinib or alectinib as second-line ALK inhibitors between 1 January 2011 and 30 September 2017 were included. Healthcare costs and resource utilization for up to 1 year of therapy were calculated on a per-patient-per-month (PPPM) basis and stratified by presence or absence of brain metastases (BM). Multivariate regression analysis was performed to identify factors associated with costs. Top ten cost drivers of non-inpatient procedure costs were recorded.Results: One hundred and twelve patients received second-line ALK inhibitors. Total mean PPPM healthcare costs were $23,984 for all patients receiving up to 1 year of post-crizotinib, second-line ALK inhibitor therapy. Total mean PPPM costs for patients with BM on or prior to post-crizotinib, second-line ALK inhibitor therapy were 1.37-times as high as those for patients without BM (p = 0.0406). Mean PPPM outpatient visits and inpatient hospitalization stays were higher for patients with BM versus no BM. The main cost drivers for non-inpatient procedures were radiation therapy, medications, and diagnostic radiology.Limitations: Analyses did not include newer ALK-directed therapies. BM development after the index date (defined as the date of the first claim for a second-line ALK inhibitor) may have been misclassified as non-BM. Findings may not be generalizable to patients with no health insurance coverage.Conclusions: Treatment of patients with ALK + NSCLC with ceritinib or alectinib as post-crizotinib, second-line ALK inhibitor therapy represents a high economic burden. Healthcare costs and resource utilization were significantly higher for patients with ALK + NSCLC with BM versus no BM.

BACKGROUND: A small proportion of Non-Small Cell Lung Cancers (NSCLC) are detected with Anaplastic Lymphoma Kinase (ALK) mutation by immunohistochemistry (IHC) but are negative by Fluorescence in situ Hybridization (FISH). Data on responses and outcome of this subset of patients when treated with crizotinib is limited. We analyzed the outcomes of such patients who received crizotinib.
METHODS: Demographics, treatment details, response to treatment, date of progression and date of death were collected for patients who were IHC positive and FISH negative for ALK mutation from a prospectively maintained database. Depending upon feasibility, patients received either platinum based doublet chemotherapy or the ALK inhibitor crizotinib as first line therapy. Outcomes were compared to our previously published historical cohort of FISH positive patients who were treated with crizotinib.
RESULTS: Thirteen patients were detected to be IHC+/FISH- and out of these seven received crizotinib. Objective response rate for crizotinib was 57.15% with an estimated mean PFS of 9.6 months (95% CI 3.8 -15.5 months). The difference in ORR of ALK IHC+/FISH- when compared to our historical cohort of ALK FISH positive treated with crizotinib was not statistically significant (57.15% vs 69.8%; P = 0.265). Estimated mean and median PFS was similar between the two cohorts (median PFS 6.0 months vs 14 months; mean PFS 9.6 months versus 14.7 months; P = 0.467).
CONCLUSIONS: NSCLCs positive for ALK mutation by IHC but not detected by FISH show good response to crizotinib and merit treatment with the same.

Despite improved progression-free survival, most patients treated with the first generation ALK inhibitor crizotinib ultimately experience central nervous system (CNS) progression. Brain metastases (BM) are associated with high clinical burden in patients with advanced anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC). In this study we estimate the real-world economic burden of BM in newly diagnosed ALK+ NSCLC patients and investigate whether alectinib, a second generation ALK inhibitor that delays CNS progression, may help reduce healthcare costs in patients with ALK+ NSCLC.
Cost of BM was measured in ALK+ NSCLC patients identified from a stacked PharMetrics Plus and MarketScan claims database from January 2008 to March 2016 and December 2015, respectively. Per patient per month (PPPM) cost of BM was calculated as the difference in baseline-adjusted total costs in patients with and without BM over a variable follow-up period of up to 24 months. Cumulative incidence of new BM was derived from 88 alectinib-treated and 93 crizotinib-treated patients without baseline BM in a randomized phase III clinical trial, ALEX (NCT02075840). Costs of BM per patient were then calculated by applying the PPPM BM cost to the number of incident BM patients in each treatment cohort.
207 patients with no BM and 198 with BM were selected from the claims database. Total cost of BM was estimated at $6,029 PPPM. 24-month cumulative incidence rates of BM from the clinical trial were 7.2% and 45.3% for alectinib and crizotinib, respectively. Over follow-up, alectinib was estimated to reduce BM-related costs by $41,434 per patient compared to crizotinib.
BM is associated with substantial economic burden. Alectinib was estimated to reduce BM-related costs by preventing or delaying the occurrence of BM compared to crizotinib.

Systemic anaplastic lymphoma kinase positive (ALK+) anaplastic large cell lymphoma with extranodal involvement (ALCL-E) is a rare form of non-Hodgkin lymphoma. No large study in the literature has compared the survival outcomes among different primary extranodal sites of involvement in ALK+ ALCL-E. We identified 1306 patients with ALK+ ALCL-E diagnosed between 2004 and 2014 in the US National Cancer Database, among whom 387 had primary extranodal site in the chest/abdomen/pelvis, 103 in the bone, 62 in the central nervous system, 134 in the head and neck and 620 in the cutaneous/soft tissue. Younger age, lower Charlson-Deyo score, lower clinical stage, receipt of chemotherapy and receipt of radiotherapy were predictors of longer overall survival. Patients with extranodal involvement of central nervous system and chest/abdomen/pelvis had shorter overall survival than those with involvement of head and neck, bone, and cutaneous/subcutaneous tissue after adjusting for confounding variables. We recommend treating these patients upfront with more aggressive therapy.