Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies.

Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing, which may provide more therapeutic options for the treatment of B-cell malignancies. Considering the unmet need of evidence on BTK inhibitors in all clinical settings and to standardize the use of BTK inhibitors available in mainland China, Taiwan, Hong Kong, and Macau regions, this consensus has been formulated for the treatment of various B-cell malignancies based on the clinical practice and available evidences on the use of BTK inhibitors. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective treatment of B-cell malignancies with BTK inhibitors.

Impact of pathological nodal staging and tumour differentiation on survival and postoperative radiotherapy in completely resected stage IIIA Non-small-cell lung cancer.

BACKGROUND: Tumour differentiation is an important index for adjuvant therapy in many cancers; however, non-small cell lung cancer (NSCLC) is an exception. Furthermore, postoperative radiotherapy (PORT) is controversial in patients with NSCLC with N0-1 and N2 disease. We aimed to evaluate the impact of tumour-related factors on overall survival (OS), cancer-specific survival (CSS), and distant control (DC) in patients with completely resected stage IIIA NSCLC. MATERIALS AND METHODS: Patients with stage IIIA non-metastatic NSCLC who underwent complete resection and adjuvant chemotherapy were identified from the Taiwan Cancer Registry (January 2007-December 2017). Logistic regression analysis was performed to determine the factors associated with PORT. Survival and relapse outcomes were compared using log-rank tests and Cox regression analysis. Sensitivity analysis was performed using propensity score-matched pairs. RESULTS: In total, 1,897 patients were included and stratified according to PORT use (PORT vs. non-PORT). After adjusting for covariates, PORT was not found to be associated with improved survival outcomes. In patients with poorly differentiated tumours and N2 disease, absolute benefits for OS (adjusted hazard ratio [aHR] 0.76), CSS (aHR 0.80), and DC (aHR 0.74) were observed. Multivariable hazard models of propensity score-matched pN2 disease and poorly differentiated tumour subgroups also showed significant survival benefit with PORT treatment. CONCLUSIONS: Patients with poorly differentiated tumours and receiving PORT for pN2 disease showed a lower risk of distant recurrence and more favourable survival outcomes in stage IIIA NSCLC with R0 resection.

Curvilinear prediction of posttraumatic growth on quality of life: a five-wave longitudinal investigation of breast cancer survivors.

PURPOSE: Do cancer survivors experience positive changes (i.e., posttraumatic growth; PTG) resulting in better quality of life? The issue has yet to yield consistent notions. This longitudinal study extends the literature on the role of PTG by examining the curvilinear relationship between PTG and Health-Related Quality of Life (HRQoL), and explored whether PTG predicts subsequent HRQoL in a quadratic relationship across 2 years following surgery. METHODS: Women with breast cancer (N = 359; Mage = 47.5) were assessed at five waves over two years. On every measurement occasion, PTG measured by the posttraumatic growth inventory and HRQoL measured by SF-36 were assessed. The five waves reflect major medical demands and related challenges in the breast cancer trajectory, in which 1-day, 3 months, 6 months, 12 months, and 24 months after surgery were adopted as the survey timing. In a series of hierarchical linear modeling (HLM) analyses, the time-lagged predictions of PTG (i.e., linear, quadratic) on HRQoL were examined, controlling demographic and medical covariates. RESULTS: The results revealed that the quadratic term of PTG consistently significantly predicted physical and mental health quality of life (PCS and MCS), while the linear term of PTG did not significantly predict PCS or MCS. CONCLUSION: With multi-wave longitudinal data, this study demonstrated that the relationship between PTG and HRQoL is curvilinear, and this finding extends to PTG's prediction of subsequent HRQoL. The quadratic relationship has critical implications for clinical assessment and intervention. Details are discussed.

Cancer-Associated Thrombosis: A Taiwanese Perspective on Therapeutic Options with Focus on Non-Vitamin K Antagonist Oral Anticoagulants.

Cancer-associated thrombosis (CAT) is a common complication of malignancies. Patients with CAT are at risk of venous thromboembolism recurrence, but also at risk of bleeding while anticoagulated. Taiwanese patients are perceived to have a lower incidence of CAT, likely leading to false reassurance for Taiwanese patients with cancer. Because of this, oncologists and cardiologists from multiple medical institutions in Taiwan have set forth to provide clinical consensus guidelines on the management of CAT, based on local clinical practices and guided by predominant international clinical practice guidelines. This paper aims to describe the current disease burden of cancer-associated venous thromboembolism in Taiwanese cancer patients, and discusses the unmet needs and gaps in the management of this medical complication. It also outlines diagnostic and management strategies relevant to the different treatment options available, such as non-vitamin K antagonist oral anticoagulants.

A Cross-sectional Study of Patients and Physicians on the Impact of Myeloproliferative Neoplasms on Patient Health: The Landmark Survey From Taiwan.

Patients with myeloproliferative neoplasm (MPN), including myelofibrosis, polycythemia vera, and essential thrombocythemia, experience a pronounced symptom burden. This study aimed to collect information from physicians and patients in Taiwan to explore their perceptions regarding MPN, treatment goals, and satisfaction with disease management. A cross-sectional, online survey was conducted among patients and physicians from September 2018 to November 2018 in Taiwan as a subset of the expansion of the Landmark survey. Overall, 50 patients with MPN and 30 physicians participated in this study. The symptom burden was low, with the mean number of symptoms experienced being 1.8. The most frequent symptom per physicians' perception was fatigue, whereas it is not the most common symptom from MPN patients' perspective. Blood count was the key indicator to determine treatment success from patients' view, whereas presence of a new symptom was the key indicator from physicians' perspective. Concordant with previous studies, our study revealed a lack of alignment between physician and patient perceptions relating to treatment goals and disease management. Nevertheless, the physical, emotional, work/activities and financial impacts on patients were minimal in Taiwan.

Long-Term Survival Effect of the Interval between Postoperative Chemotherapy and Radiotherapy in Patients with Completely Resected Pathological N2 Non-Small-Cell Lung Cancer.

(1) Purpose: To investigate the effects of the time interval between initiation of adjuvant chemotherapy and radiotherapy on survival outcomes in patients with completely resected stage IIIA pN2 non-small-cell lung cancer (NSCLC); (2) Methods: Data on 2515 patients with completely resected stage IIIA pN2 NSCLC in 2007-2017 were extracted from the Taiwan Cancer Registry Database. The survival outcomes in patients who underwent concurrent chemoradiotherapy (CCRT) and sequential chemotherapy and radiotherapy (SCRT) with either a short (SCRT1) or long (SCRT2) interval between treatments were estimated using Kaplan-Meier, Cox regression, and propensity score matching (PSM); (3) Results: Multivariate analyses of OS showed that SCRT2 (hazard ratio [HR] 0.64, p = 0.017) was associated with improved overall survival (OS). After PSM, the median OS periods were 64 and 75 months in the SCRT1 and SCRT2 groups, respectively, which differed significantly from that of 58 months in the CCRT group (p = 0.003). In elderly patients, SCRT2 significantly improved survival relative to CCRT before PSM (p = 0.024) and after PSM (p = 0.002); (4) Conclusions: A longer interval between initiation of adjuvant chemotherapy and postoperative radiotherapy (PORT; SCRT2) improved OS relative to CCRT; the benefits were greater in elderly patients (age >60 years).

The Double-Edged Sword of Reflective Pondering: The Role of State and Trait Reflective Pondering in Predicting Depressive Symptoms Among Women With Breast Cancer.

BACKGROUND AND PURPOSE: Prior research has debated whether reflective pondering is a more constructive form of rumination than brooding, which is generally considered maladaptive. This study sought to investigate whether reflective pondering predicts depressive symptoms and whether reflective pondering is adaptive under certain conditions. We predicted that the effectiveness of reflective pondering could depend on concurrent coping strategies and the trait-state distinction. METHOD: Women with breast cancer (N = 309; M age = 47.5) were assessed at four waves over 2 years. A time-lagged design was applied, with rumination (i.e., brooding and reflective pondering) and coping (i.e., engagement and disengagement) measured from T1 to T3, predicting depressive symptoms assessed from T2 to T4. These variables were measured by the Ruminative Response Scale, the Brief COPE, and the Hospital Anxiety and Depression Scale. RESULTS: Using hierarchical linear modeling, brooding, but not reflective pondering, predicted elevated depressive symptoms at both between- and within-person levels. The relationship between reflective pondering and depression was moderated by the coping strategies. Individual differences in reflective pondering predicted worse depressive symptoms, but higher use of engagement coping mitigated the detrimental effect. Within individuals, the co-occurrence of reflective pondering and disengagement coping predicted a subsequent decrease in depressive symptoms. CONCLUSIONS: The emerging role of reflective pondering in the face of breast cancer-related stress appears to be a double-edged sword. Its impact on depression may depend on concurrent coping strategies and whether reflective pondering is assessed at state and trait levels.

Therapeutic Efficacy and Inhibitory Mechanism of Regorafenib Combined With Radiation in Colorectal Cancer.

BACKGROUND: Although both chemotherapy and radiotherapy (RT) can sufficiently maintain tumor suppression of colorectal cancer (CRC), these treatments may trigger the expression of nuclear factor kappa B (NF-κB) and compromise patients' survival. Regorafenib suppresses NF-κB activity in various tumor types. However, whether regorafenib may act as a suitable radiosensitizer to enhance therapeutic efficacy of RT remains unknown. MATERIALS AND METHODS: Here, we established a CRC-bearing animal model to investigate the therapeutic efficacy of regorafenib in combination with RT, through measurement of tumor growth, body weight, whole-body computed tomography (CT) scan and immunohisto-chemistry staining. RESULTS: Smallest tumor size and weight were found in the combination treatment group. In addition, RT-induced up-regulation of NF-κB and downstream proteins were diminished by regorafenib. Moreover, the body weight and liver pathology in the treated group were similar to those of the non-treated control group. CONCLUSION: Regorafenib may enhance the anti-CRC efficacy of RT.

Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis.

INTRODUCTION: The primary analysis of a global phase 3 study that evaluated the efficacy and safety of denosumab versus zoledronic acid for preventing skeletal-related events (SREs) in adults with newly diagnosed multiple myeloma (MM) indicated that denosumab was noninferior to zoledronic acid for time to first on-study SREs. Here we present a subgroup analysis to evaluate efficacy and safety in Asian patients. METHODS: Patients were randomized 1:1 to receive denosumab 120 mg subcutaneously or zoledronic acid intravenously 4 mg every 4 weeks in a double-blind, double-dummy fashion. All patients received standard-of-care first-line antimyeloma treatment. Each patient received either study drug until an estimated 676 patients experienced at least one on-study SRE and the primary efficacy and safety analyses were completed. RESULTS: Of 1718 total enrolled patients, 196 Asian patients (denosumab, n = 103; zoledronic acid, n = 93) were included in this subgroup analysis. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% and 50.5%, respectively (HR [95% CI], 0.77 [0.48-1.26]). All 194 patients receiving at least one dose of study drug experienced at least one treatment-emergent AE. The most common AEs reported in either group (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), and pyrexia (38.2%, 41.3%). Treatment-emergent renal toxicity occurred in 9/102 (8.8%) and 20/92 (21.7%) patients, respectively. Similar rates of positively adjudicated osteonecrosis of the jaw (7 [6.9%] vs 5 [5.4%]) and treatment-emergent hypocalcemia (19 [18.6%] vs 17 [18.5%]) were reported in the denosumab and zoledronic acid groups, respectively. CONCLUSION: Efficacy and safety outcomes from this Asian subgroup were comparable to those of the full study population. Overall, this analysis supports denosumab as an additional treatment option for standard of care for Asian patients with newly diagnosed MM with lytic bone lesions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01345019.

A nationwide survey of fatigue in cancer patients in Taiwan: an unmet need.

BACKGROUND: Cancer-related fatigue (CRF) is an emerging clinical issue, although its prevalence and impact on quality of life (QOL) in cancer patients in Taiwan remain unclear. The present nationwide cross-sectional study was conducted to provide a thorough overview of the prevalence, related factors and impact of CRF in Taiwan. METHODS: In this multi-center survey, data were collected using the International Classification of Diseases 10th Revision (ICD-10) Fatigue evaluation, Brief Fatigue Inventory-Taiwan (BFI-T), the Chinese version of the Symptom Distressed Scale and a fatigue experience survey. Logistic regression was used to determine the correlations between fatigue characteristics and the factors studied. RESULTS: A total of 1207 cancer patients were recruited from 23 hospitals in Taiwan. Fatigue was the most distressing symptom in Taiwanese cancer patients. The distress score was higher if CRF was diagnosed using ICD-10 compared with BFI-T. Rest and nutritional supplementation were the most common non-pharmacological treatments; blood transfusion was the most common pharmacological treatment. There were 45% of patients reported not receiving a timely intervention for fatigue. CONCLUSIONS: Fatigue is the most bothersome symptom reported by Taiwanese cancer patients. Caregivers should be aware of the impact of CRF on QOL in cancer patients, constantly measure the severity of fatigue and provide appropriate interventions.

Satisfaction with pain management and impact of pain on quality of life in cancer patients.

AIM: To evaluate the prevalence of pain in cancer outpatients in Taiwan and to investigate the impact of pain on quality of life (QoL) and patient satisfaction. Results were compared to those of a similarly designed study conducted in 2008 to identify trends. METHODS: Adult patients with cancer treated as outpatients in hospitals throughout Taiwan were recruited. Pain intensity and the extent to which pain interfered with QoL were self-reported using a modified version of the Brief Pain Inventory. Patients also indicated their level of satisfaction with their physician, as well as with their pain control. RESULTS: A total of 2652 patients were enrolled from 16 sites. Of these, 1167 (44.0%) patients reported experiencing pain during the previous week. Prevalence and severity of pain were highest in patients with progressive disease. A higher pain severity score was significantly associated with greater interference in both physical and psychological functions. Overall, 86.0% of all participants expressed satisfaction with their physician and 84.8% were satisfied with their pain control; satisfaction rates were associated with pain severity. Compared with the findings from the 2008 study, pain prevalence was notably lower and patient satisfaction was significantly greater in the current study. CONCLUSIONS: Prevalence and severity of pain were associated with disease stage. Pain interference on QoL correlated significantly with pain severity. Treatment of pain in cancer patients in Taiwan seems to have improved from 2008 to 2014, possibly attributable to new cancer pain treatment guidelines and the wider availability of novel analgesic therapies.

Bortezomib therapy in a real-world setting in patients with relapsed or refractory multiple myeloma.

Bortezomib is a proteasome inhibitor, approved for treating newly diagnosed and relapsed multiple myeloma (MM). This realworld, multicenter, observational, non-interventional study of bortezomib was designed to collect and analyze prospective data in Taiwanese patients with relapsed or refractory MM. The primary endpoints included clinical effectiveness outcomes (disease response, disease progression [PD], time-to-response, time-toprogression, response duration, and overall survival [OS]). Secondary endpoints were safety and healthcare resource utilization. Total 100 patients (median [range] age 64.9 [37.0-85.5] years) were enrolled; 47 patients completed the study. Of the withdrawn patients (n=53), there were 48 deaths (PD-related death: n=35, adverse events [AEs]-related: n=12, other reason: n=1), and 5 due to loss to follow-up. Four patients in Cycle 1, 6 patients each in Cycle 2 and 5, 7 in Cycle 3, 10 patients in Cycle 4, 5 patients in Cycle 6, and 3 patients each in Cycle 7 and 8 achieved overall response during the study. Time-to-response was 4.68 months (95%CI: 3.2, NE) and response duration was 10.08 months (95%CI: 2.3, 28.6). Median OS was 9.8 months (95%CI: 3.8, 13.7), and median time-to-progression was 11.3 months (95%CI: 6.2, 20.2). Most common non-hematological AEs were diarrhea (n=32) and hypoesthesia (n=25); most common hematological AE was thrombocytopenia (n=18). Efficacy and safety profile of bortezomib in Taiwanese patients with MM was similar to global and other Asian population. Study provides a critical insight on use of bortezomib in realworld clinical practice, which can be helpful for Taiwanese healthcare providers' decision-making processes.

Karnofsky Performance Status as A Predictive Factor for Cancer-Related Fatigue Treatment with Astragalus Polysaccharides (PG2) Injection-A Double Blind, Multi-Center, Randomized Phase IV Study.

Fatigue is a common and debilitating symptom in patients with advanced cancer, resulting in poor quality of life and reduced treatment efficacy. Phytotherapeutic agents have shown potential effects to relieve cancer-related fatigue in these patients. The aim of this study was to evaluate the efficacy and safety of Astragalus Polysaccharides injection and identify predictive factors associated with this treatment. Patients with advanced cancer receiving palliative care with moderate to severe cancer-related fatigue were enrolled in this study for two treatment cycles. Fatigue improvement response rates were analyzed as the primary endpoint at the end of the first cycle to determine treatment efficacy. The drug safety profile was evaluated by the reporting of adverse events. Three hundred and ten patients were enrolled in this study and 214 patients were included ITT population. Improvement in fatigue scores by at least 10% was observed in greater than 65% of subjects after one treatment cycle compared to scores at baseline. Patients with higher Karnofsky Performance Status (KPS) responded better to the Astragalus Polysaccharides injection. Drug-related adverse event rates were less than 9%. This study identified KPS as a promising predictive factor for the therapeutic efficacy of Astragalus Polysaccharides injection.

Patients with head and neck cancer may need more intensive pain management to maintain daily functioning: a multi-center study.

PURPOSE: The purpose of this study is to investigate the prevalence of pain, pain management, and impact of recent pain on daily functioning in patients with head and neck cancer (HNC) and patients with other cancers. METHODS: This multi-center survey was conducted by using Brief Pain Inventory questionnaire to evaluate pain status and its impact on daily functioning. RESULTS: A total of 3289 patients were analyzed including 708 HNC patients and 2581 patients with other cancers. The overall pain prevalence was 69.17%. A higher percentage of HNC patients had recent pain (60.59 vs. 44.01%, P < 0.001), required pain management (86.29 vs. 72.03%, P < 0.001), and used any analgesics (53.81 vs. 34.52%, P < 0.001). HNC patients with pain management had a higher prevalence of recent pain (85.83 vs. 81.14%, P = 0.044) and a slightly lower satisfaction rate (74.00 vs. 79.70%, P = 0.070). Regarding the impact of pain on daily functioning, HNC patients had a lower mean interference score for general activity such as walking, normal work, sleep, and life enjoyment. CONCLUSIONS: The HNC patients may need more intensive pain management to achieve optimal pain control and maintain daily functioning.

Long-term safety and efficacy of deferasirox in patients with myelodysplastic syndrome, aplastic anemia and other rare anemia in Taiwan.

OBJECTIVE: Patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemia require chronic blood transfusions which can lead to iron overload and subsequent excess iron-mediated complications. Intensive iron chelation with deferasirox could remove excess iron and can alleviate these events; however, the long-term safety and efficacy in Chinese population are not clearly characterized. This study examined the long-term efficacy and safety of deferasirox in a real-world setting in Taiwan. METHODS: This observational, non-interventional, single-arm, multi-center, phase IV study was designed to collect the safety and clinical information about patients who were treated with deferasirox according to investigator's judgment and in accordance with the general clinical practice. RESULTS: From 2009 to 2011, patients with MDS (N = 38), AA (N = 23), and other rare anemias (N = 18) were enrolled. The mean deferasirox exposure was 17.7 ± 4.02 mg/kg/day. The most common drug-related AEs were skin disorders (32.9%) and gastrointestinal disorders (30.4%), while grade 3-4 AEs were rare (5.1%). In the overall patient population, deferasirox effectively decreased serum ferritin levels at 1 year (P = 0.0154) and 3 years (P = 0.0424) from the baseline. Upon the use of deferasirox, 32.9% patients showed erythroid response and 16.7% patients had platelet response. CONCLUSIONS: For patients with MDS, AA, and other rare anemias, the AEs observed in this 3-year surveillance study with deferasirox were mostly mild or moderate. In addition, the hematological response rate was higher than that in the EPIC study, which primarily enrolled Caucasian patients.

A nationwide survey of adherence to analgesic drugs among cancer patients in Taiwan: prevalence, determinants, and impact on quality of life.

PURPOSE: Poor adherence to analgesic drugs is one of the most common barriers to adequate pain management. This prospective, cross-sectional, patient-oriented observational study aimed to explore the adherence rate, clinical factors, and impact of adherence to analgesic drugs on the quality of life (QoL) among cancer outpatients in Taiwan. METHODS: Eight hundred ninety-seven consecutive adult outpatients with cancer who had reported tumor pain and received regular analgesic drug treatment were enrolled from 16 medical centers across Taiwan. The Brief Pain Inventory was used to assess pain intensity and QoL. Morisky's four-item medication adherence scale was used to assess adherence to analgesic drugs. Clinical factors possibly associated with good adherence to analgesic drugs were analyzed using multivariate logistic regression analyses. RESULTS: Of the 897 patients, 26.9% met criteria for the good, 35.5% for the moderate, and 37.6% for the poor adherence groups. The good adherence group had significantly better QoL outcomes than the moderate and poor adherence groups (all p < 0.05). Age ≥ 50 years, head and neck or hematological malignancies, cancer-related pain, patients who agreed or strongly agreed that the side effects of analgesic drugs were tolerable, and patients who disagreed or strongly disagreed that the dosing schedule could be flexibly self-adjusted to deal with the actual pain were predictors of good adherence to analgesic drugs. CONCLUSIONS: Awareness of the clinical factors associated with adherence to analgesic drugs may help clinicians to identify cancer patients at a greater risk of non-adherence, reinforce optimal pain management, and improve the QoL by enhancing adherence to pain medications.

Outcomes for Cervical Cancer Patients Treated With Radiation in High-Volume and Low-Volume Hospitals.

PURPOSE: To investigate the effects of different hospital patient loads on the standard of care and treatment outcomes of patients with cervical cancer treated primarily with radiation therapy and to identify factors that may contribute to survival differences among hospitals. METHODS AND MATERIALS: We used the Taiwan Cancer Registry database to extract data on a total of 2582 International Federation of Gynecology and Obstetrics stage IB to IVA patients with uterine cervical cancer diagnosed from 2007 to 2013 who underwent primarily curative radiation therapy (with or without chemotherapy). We explored associations among hospital patient loads, clinical parameters, the type of care given, and survival. RESULTS: Patients who received treatment at hospitals with small and medium patient loads (≤5 cases annually) were older and had more advanced-stage disease than other patients. Positive associations were evident between the use of chemotherapy and brachytherapy and hospital patient load. Patients treated at hospitals with large patient loads (>5 cases annually) experienced better overall survival than those treated at hospitals with small or medium patient loads (P < .001). Stepwise addition of variables to multivariable analyses indicated that greater use of chemotherapy and brachytherapy were major contributors to the better survival of patients treated at hospitals with large patient loads. However, larger hospital patient load per se (>5 vs ≤5 cases annually) was also independently prognostic for better survival of patients with bulky tumors or advanced-stage disease. CONCLUSIONS: We found that the inferior survival rate of patients with cervical cancer treated at hospitals with smaller patient loads was attributable not only to a lower standard of care in such hospitals but also to the smaller patient load. Our findings indicate how treatment should be improved in hospitals with small and medium patient loads.

Safety and efficacy of nilotinib in routine clinical practice in patients with chronic myeloid leukemia in chronic or accelerated phase with resistance or intolerance to imatinib: results from the NOVEL study.

BACKGROUND: Nilotinib, a second-generation tyrosine kinase inhibitor (TKI), is approved for the treatment of patients with chronic myeloid leukemia (CML) in many countries, including Taiwan. Though a number of controlled clinical trials have demonstrated the safety and efficacy of nilotinib, studies assessing the safety and efficacy of nilotinib in routine clinical practice are limited. METHODS: The current study was an open-label, single-arm study conducted across 12 centers in Taiwan in adult patients with CML in chronic or accelerated phase with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to one or more previous TKIs. The primary objective was to collect the long-term safety data in patients treated with nilotinib 400 mg, twice daily for up to 2 years. RESULTS: The study enrolled 85 patients with CML, including 76 in the chronic phase (CML-CP) and 9 in the accelerated phase (CML-AP). Overall, 1166 adverse events (AEs) were reported in 80 patients (94.1%), of which 70 AEs (6%) in 28 patients (32.9%) were serious and 336 AEs (28.8%) reported in 60 patients (70.6%) were drug-related. Common drug-related AEs were thrombocytopenia (21.2%), increased alanine aminotransferase (21.2%) and pruritus (17.7%). Of the 85 patients, 19 switched from imatinib due to intolerance - AEs were resolved in 16 of these 19 patients (84.2%). By 24 months, the cumulative rates of complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0 (BCR-ABL1IS ⩽0.01%) and MR4.5 (BCR-ABL1IS ⩽0.0032%) were 75.3, 56.8, 16.2 and 7.4%, respectively. Patients with CML-CP at baseline had higher overall survival (OS) and progression-free survival (PFS) than those with CML-AP. CONCLUSION: This is the first study that demonstrated that nilotinib is effective and well-tolerated in patients resistant or intolerant to imatinib in the real-world setting in Taiwan, reflecting effective management of CML by physicians under routine clinical practice in Taiwan.

Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection.

BACKGROUND & AIMS: Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation. METHODS: We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation. RESULTS: HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (≥6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio [HR] 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92-76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15-5.05; p = 0.02). CONCLUSIONS: Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients. LAY SUMMARY: In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources. Clinical trial number: NCT 00931229.