Wei Li

Chronic myeloid leukemia in the Asia-Pacific region: Current practice, challenges and opportunities in the targeted therapy era

Chronic myeloid leukemia (CML) management varies across Asia due to disparities in affluence and healthcare provision. We surveyed CML management practice at 33 hospitals in 14 countries/regions to identify treatment challenges and opportunities for harmonization. Patients were generally treated according to international guidelines; however, tyrosine kinase inhibitors (TKIs) and molecular monitoring are inaccessible to many patients not covered by national insurance or eligible for subsidized treatment. Late diagnosis and suboptimal monitoring, often due to cost and accessibility issues, are challenges. Priorities for Asia include: extending accessibility to TKIs; specialist laboratory monitoring; and enriching data to support regional CML management guidelines.

Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer

BackgroundExtensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority.MethodsFrom June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60xa0mg/m2, day 1) and amrubicin (40xa0mg/m2, days 1–3) once every 21xa0days. EP-treated patients received cisplatin (80xa0mg/m2, day 1) and etoposide (100xa0mg/m2, days 1–3) once every 21xa0days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal.ResultsMedian overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3xa0months (pu2009=u20090.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95xa0% confidence interval for hazard ratio 0.63–1.03xa0months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7xa0months (pu2009=u20090.35) and 69.8xa0% vs. 57.3xa0%, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4xa0%; EP 44.0xa0%). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable.ConclusionsAP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5xa0months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China.Trial registrationThis trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504).

Circularly permuted TRAIL plus thalidomide and dexamethasone versus thalidomide and dexamethasone for relapsed/refractory multiple myeloma: a phase 2 study

PurposeCircularly permuted TRAIL (CPT) has exhibited promising efficacy as a mono-therapy or in combination with thalidomide for patients with multiple myeloma (MM). In this phase 2 study, the safety and efficacy of CPT in combination with thalidomide and dexamethasone (CPTxa0+xa0TD) was evaluated in patients with pretreated relapsed/refractory MM (RRMM).MethodsPatients who received at least two previous therapies for MM were randomly assigned at a 2:1 ratio to receive treatment with CPTxa0+xa0TD or thalidomide and dexamethasone (TD). The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), duration of response (DOR) and safety.ResultsOverall, 47 patients were assigned to the CPTxa0+xa0TD group, and 24 patients were recruited to the TD group. The ORR in the CPTxa0+xa0TD group was 38.3 vs. 25.0% in the TD group. The median PFS time was 6.7xa0months for the CPTxa0+xa0TD group and 3.1xa0months for the TD group. The median DORs for the CPTxa0+xa0TD and TD groups were 7.1 and 3.2xa0months, respectively. Most of the adverse effects (AEs) were grade 1 or 2. Serious AEs were reported in 19.7% of the patients. No treatment-related deaths were reported.ConclusionCPT plus TD could serve as a new therapeutic strategy for patients with RRMM. A randomized, double-blind, placebo-controlled confirmatory study is currently under way.

Standardized fluorescence in situ hybridization testing based on an appropriate panel of probes more effectively identifies common cytogenetic abnormalities in myelodysplastic syndromes than conventional cytogenetic analysis: A multicenter prospective study of 2302 patients in China

In an attempt to establish the advantages of fluorescence in situ hybridization (FISH) studies over conventional cytogenetic (CC) analysis, a total of 2302 de novo MDS patients from 31 Chinese institutions were prospectively selected in the present study for both CC and standardized FISH analysis for +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities. CC analysis was successful in 94.0% of the patients; of these patients, 35.9% of the cases were abnormal. FISH analysis was successful in all 2302 patients and detected at least one type of common cytogenetic abnormality in 42.7% of the cases. The incidences of +8, -7/7q-, -5/5q-, 20q- and-Y chromosomal abnormalities by FISH were 4.1% to 8.7% higher than those by CC. FISH identified abnormalities in 23.6% of the patients exhibiting normal CC results and revealed that 20.7% of the patients with adequate normal metaphases (≥20) had abnormal clones. FISH identified cytogenetic abnormalities in 50.4% of the patients with failed CC analysis. In summary, our multicenter studies emphasised and confirmed the importance of applying standardized FISH testing based on an appropriate panel of probes to detect common cytogenetic abnormalities in Chinese de novo MDS patients, particularly those with normal or failed CC results.

Rituximab plus chemotherapy as first-line treatment in Chinese patients with diffuse large B-cell lymphoma in routine practice: a prospective, multicentre, non-interventional study

BackgroundThe efficacy and safety of rituximab-based chemotherapy (R-chemo), the standard regimen for patients with diffuse large B-cell lymphoma (DLBCL), which is more common in Asia than in Western countries, are well confirmed in randomized controlled trials (RCTs). However, the safety and effectiveness of R-chemo in patients who are largely excluded from RCTs have not been well characterized. This real-world study investigated the safety and effectiveness of R-chemo as first-line treatment in Chinese patients with DLBCL.MethodsTreatment-naive DLBCL patients who were CD20 positive and eligible to receive R-chemo were enrolled with no specific exclusion criteria. Data collected at baseline included age, gender, disease stage, international prognostic index (IPI), B symptoms, extranodal involvement, performance status, and medical history. In the present study, data on safety, treatment effectiveness, and HBV infection management were collected 120xa0days after the last R-chemo administration.ResultsOverall, R-chemo was well tolerated. The safety profile of R-chemo in patients with a history of heart or liver disease was well described without any additional unexpected safety concerns. The overall response rate (ORR) in the Chinese patients from this study was 94.2xa0% (complete response [CR], 55.0xa0%; CR unconfirmed [CRu] 18.2xa0%; and partial response [PR], 20.9xa0%). Compared to patients with no history of disease, the CR and PR rates of patients with a history of heart or liver disease were lower and higher, respectively; this tendency could be in part explained by treatment interruptions in patients with heart or liver diseases. HBsAg positivity and a maximum tumor diameter of ≥7.5xa0cm negatively correlated with CRu2009+u2009CRu, whereas age and HBsAg positivity negatively correlated with CR.ConclusionsThis study further validated the safety and effectiveness of R-chemo in Chinese patients with DLBCL. Patients with a history of heart or liver disease may further benefit from R-chemo if preventive measures are taken to reduce hepatic and cardiovascular toxicity. In addition to IPI and tumor diameter, HBsAg positivity could also be a poor prognostic factor for CR in Chinese patients with DLBCL.Trial registrationClinicalTrials.gov #NCT01340443, April 20, 2011.

Comparison of Clinical Efficacy of Cytarabine with Different Regimens in Postremission Consolidation Therapy for Adult t(8;21) AML Patients: A Multicenter Retrospective Study in China

Background: The survival of patients with acute myeloid leukemia (AML) with t(8;21) was reported to be shorter in China than in other countries. Patients: We analyzed the correlation between different cytarabine (Ara-c) regimens and outcome in 255 t(8;21) AML patients in China who received postremission consolidation chemotherapy only. Results: The 5-year overall survival (OS) of the high-dose Ara-c group (HDAC; 2≤ Ara-c ≤3 g/m2), intermediate-dose Ara-c group (MDAC; 1.0≤ Ara-c <2.0 g/m2), low-dose Ara-c group (LDAC; 0.2< Ara-c <1.0 g/m2) and standard-dose Ara-c group (SDAC; 0.1≤ Ara-c ≤0.2 g/m2) were 65.3, 39.4, 25.2 and 27.9%, respectively (p = 0.003). In the HDAC group, but not in the MDAC group, the 5-year OS of patients who achieved 3-4 cycles of chemotherapy was superior to those who underwent 1-2 cycles (84.4 vs. 43.6%, p < 0.05), and the 3-year OS of patients who achieved an accumulated 36 g/m2 of Ara-c was significantly higher compared to those who did not (85.3 vs. 39.2%, p < 0.05). Multivariate analysis indicated that factors such as WBC >3.5 × 109/l, PLT ≤30 × 109/l, and extramedullary infiltration were associated with a poor prognosis. Conclusion: The survival of t(8;21) AML patients treated with high-dose Ara-c (≥2 g/m2) was superior to other dose levels in postremission consolidation chemotherapy. Patient survival was improved by 3-4 cycles of chemotherapy with an accumulated concentration of 36 g/m2 of Ara-c. WBC >3.5 × 109/l, PLT ≤30 × 109/l and extramedullary infiltration could be indicative of a poor clinical prognosis.

Three-year Follow-up on the Safety and Effectiveness of Rituximab Plus Chemotherapy as First-Line Treatment of Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in Real-World Clinical Settings in China: A Prospective, Multicenter, Noninterventional Study

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50–67%) for DLBCL patients and 46% (95% CI: 20–69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration: ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.

Effectiveness and Tolerability of Micafungin in Chinese Patients with Invasive Fungal Infections: A Retrospective, Multicenter Study

IntroductionInvasive fungal infections (IFIs) are a significant health problem in immunocompromised patients, resulting in substantial morbidity, mortality, and healthcare costs. Micafungin is a broad-spectrum echinocandin with activity against Candida and Aspergillus spp. This was a multicenter, non-comparative, retrospective observational study that evaluated the effectiveness and tolerability of intravenously administered micafungin for treating IFIs caused by Candida and Aspergillus spp.MethodsAdult patients in China who had received at least one dose of intravenously administered micafungin were eligible. Retrospective data (May 2008–April 2015) were extracted from patients’ medical files and recorded using electronic data capture. The primary endpoint was overall success rate (patients with complete or partial response). Subgroup analyses determined effectiveness according to diagnostic certainty, fungal species, type of IFI, duration of micafungin treatment, and daily dose of micafungin. Tolerability, including the incidence of adverse events (AEs), was also assessed.ResultsOverall, 2555 patients who received at least one dose of micafungin were identified. The mean duration of treatment and mean daily dose were 10.2xa0days and 133.0xa0mg, respectively. The overall success rate was 60.8%; this was significantly higher in patients who received treatment for at least 1xa0week (range 67.9–71.6% [mean 69.2%]) compared with less than 1xa0week (47.8%; Pu2009<u20090.0001), and those who received 50–100xa0mg (65.7%) compared with other daily doses (range 42.9–60.1% [mean 59.0%]; Pu2009=u20090.0011). Success rates in Candida- and Aspergillus-infected patients were similar (61.9% and 56.8%, respectively). AEs and adverse drug reactions were observed in 36.2% and 4.5% of patients, respectively. The majority of AEs were mild, while discontinuation due to AEs was low (2.3%).ConclusionMicafungin is effective and well tolerated for the treatment of patients with IFIs in China, as demonstrated in Candida- and Aspergillus-infected adults. Subgroup analyses highlighted the potential benefits of treating IFIs with micafungin for a minimum of 1xa0week.Trial registrationClinicalTrials.gov identifier NCT02678598.FundingAstellas Pharma Inc.