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.

Elevated serum IL-13 level is associated with increased Treg cells in tumor microenvironment and disease progression of diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoid malignancy, with an immunosuppressive microenvironment affecting clinical outcome. Interleukin (IL)-13 overexpression is observed in multiple solid tumors and contributes to tumor progression. This study aims to investigate pretreatment serum IL-13 levels and their relationship with the prognosis of DLBCL patients. One hundred and sixty-six patients with newly diagnosed DLBCL from June 2015 to July 2017 were included. Patients with elevated pretreatment serum IL-13 levels (IL-13≥1.63 pg/ml) were classified into the high IL-13 group and they had significantly lower complete remission rate (60% vs. 74%, p = 0.0059), higher progression rate (43% vs. 23%, p = 0.0051), and poor progression-free survival (2-year PFS, 63% vs. 78%, p = 0.0078) and overall survival (2-year OS, 75% vs. 92%, p = 0.0027), when compared to those in the low IL-13 group (IL-13<1.63 pg/ml). Meanwhile, increased Treg cell ratio in peripheral blood (p = 0.0147) and elevated serum IL-2 levels (p = 0.0272) were observed in the high IL-13 group. Moreover, RNA sequencing data showed that patients in the high IL-13 group had significantly elevated expression of chemokines and chemokine receptors (CCR4, CCL19, CCL21, CXCL2) related to Treg activation and recruitment. Consistent with the chemokine profile, tumor immunophenotyping analysis revealed that higher Treg cells recruitment in the high IL-13 group than the low IL-13 group (p = 0.0116). In vitro, when lymphoma cells co-cultured with peripheral blood monocytes of healthy controls, metformin down-regulated both IL-13 level and Treg cell ratio, in consistent with the decreased serum IL-13 levels of patients after 6 months of metformin maintenance therapy in the high IL-13 group. Taken together, pretreatment serum IL-13 level is related to the immunosuppressive microenvironment and poor clinical outcome of DLBCL patients and could be targeted by metformin, thus providing a new therapeutic strategy in treating DLBCL with high serum IL-13 levels.

A Multi-Center, Real-World Study of Chidamide for Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas in China.

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1-2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

Chronic kidney disease: prevalence and association with handgrip strength in a cross-sectional study.

BACKGROUND: Poor physical function is strongly associated with mortality and poor clinical outcomes in adults with chronic kidney disease (CKD). Handgrip strength (HGS) is an important index for physical function in the general population, and the association between HGS and CKD is worth investigating. METHODS: From September to November 2015, we conducted a cross-sectional study consisting of 10,407 participants in Jurong City, China. Age-related and sex-specific HGS percentile curves were constructed using the GAMLSS method. In addition, logistic regression was applied to estimate the association between HGS and the presence of CKD with odds ratios (ORs) and 95 % confidence intervals (CIs). RESULTS: Participants with low HGS tended to be older and were more likely to have CKD (8.73 %). Smoothed centile curves of HGS showed a similar shape in both sexes: participants peaked at approximately 20-35 years old and gradually decreased after the age of 50. In addition, independent of age and other factors, the decreased presence of CKD was significantly identified in individuals with moderate (OR: 0.64, 95 % CI: 0.49-0.83) and high HGS (OR: 0.37, 95 % CI: 0.23-0.58). CONCLUSIONS: We concluded that HGS was significantly negatively associated with CKD in Chinese community-dwelling persons.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.

BACKGROUND: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. METHODS: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. RESULTS: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. CONCLUSION: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.

Time trend of cardiometabolic risk factors over a 10-year period in the office-working population in China.

OBJECTIVES: Recent dramatic increases in cardiovascular disease mortality in China can be mostly explained by adverse changes in hypertension, dyslipidaemia, diabetes and obesity, known as cardiometabolic risk factors. Our study aimed to assess the trend of these four signatures by a 10-year lag in Nanjing, China. METHODS: 8017 subjects attended the routine health examination in 2008, and 9379 subjects in 2017, from multiple work units of Nanjing, were included in the present study. The prevalence and trend of four cardiometabolic risk factors: hypertension, dyslipidaemia, diabetes and obesity were analysed. RESULTS: From 2008 to 2017, the prevalence of hypertension declined, while the prevalence of dyslipidaemia, diabetes and obesity increased. Besides, the population in 2008 and 2017 had an average of 0.66 and 0.78 risk factors, respectively. CONCLUSION: Cardiometabolic risk factors are common for the staff in administrative agencies and institutions of Nanjing, China. Effective screening and interventions against these risk factors should be adopted in high-risk populations such as the office-working population in China.

Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety.

Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). In 2007, a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients. This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment. The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total = 140 mg/ day), respectively. The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1% (versus 50.8% at 18 months), and the median time to MCyR was 12.7 weeks. All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response. The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64% (16/25), with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up; the median time to CHR was 16.4 weeks. The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months. The most frequently reported AEs (any grade) included pleural effusion, headache, and myelosuppression. These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.

An observational study of Chinese adults with relapsed/refractory Philadelphia-negative acute lymphoblastic leukemia.

AIM: Chinese adults with relapsed/refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (Ph- ALL) have poor outcomes. PATIENTS & METHODS: We conducted a nationwide, retrospective, observational study to assess outcomes in this patient population. RESULTS: Of the 270 enrolled patients, 31% of patients at last salvage achieved complete remission (CR) or CR with partial hematologic recovery (CRh), with median time to CR/CRh of 30 days and median CR/CRh duration of 2.7 months. The CR/CRh rate was more favorable with earlier versus later lines of salvage (41, 24 and 17% at first, second and third or later salvages, respectively). CONCLUSION: This dataset serves as an important reference of real-world outcomes using currently available chemotherapy regimens for high-risk Chinese adults with relapsed/refractory Ph- ALL.

Effects of parathyroidectomy on blood bone markers and heart rate variability in patients with stage 5 chronic kidney disease.

PURPOSE: Decreased heart rate variability (HRV) is closely related to abnormal cardiac autonomic nervous function, especially sympathetic hyperactivity, which intensifies the risk of cardiovascular events and sudden death. HRV parameters are lower in chronic kidney disease (CKD) and parathyroidectomy (PTX) can improve these abnormalities in severe secondary hyperparathyroidism (SHPT) patients. However, few studies have evaluated correlations between circulating bone markers and HRV in CKD patients. METHODS: We conducted a cross-sectional study including 134 stage 5 CKD patients with 100 controls and a prospective study of 29 PTX patients with follow-up. Circulating bone biomarkers included: (1) intact parathyroid hormone (iPTH) as bone remodeling regulator; (2) bone-specific alkaline phosphatase (BAP), representing bone formation; (3) tartrate-resistant acid phosphatase 5b (TRACP-5b), indicating bone resorption; and (4) bone-derived hormone, fibroblast growth factor 23 (FGF23). RESULTS: Stage 5 CKD patients had higher circulating iPTH, BAP, TRACP-5b, and FGF23 than controls and these bone markers were significantly elevated in SHPT patients. Baseline iPTH, BAP, and lnFGF23 were independently associated with HRV in CKD patients. After PTX with a follow-up (median interval: 6.7 months), high blood iPTH, BAP, TRACP-5b, FGF23, and attenuated HRV were ameliorated. Furthermore, improved HRV indices were associated with reduced iPTH, BAP, TRACP-5b, and FGF23. CONCLUSIONS: Circulating bone markers are correlated with HRV in CKD 5 patients and PTX can improve decreased HRV, which are associated with corrected bone markers in severe SHPT patients. Thus, we propose that PTH increases sympathetic tone and both high circulating PTH levels and sympathetic hyperactivity increase bone turnover, and that the products of bone turnover influence HRV.

Association of Thyroid Function With the Estimated Glomerular Filtration Rate in a Large Chinese Euthyroid Population.

BACKGROUND/AIMS: We aimed to explore whether thyroid function within a normal range is associated with the estimated glomerular filtration rate (eGFR) and the incidence of chronic kidney disease (CKD) in a large Chinese population. METHODS: We conducted a cross-sectional study that included 10,859 euthyroid individuals who underwent an annual regular health checkup in Jiangsu Province Official Hospital between August 2012 and August 2013. We measured the thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels using a Roche modular analytics E170 and then calculated the eGFR using the Chinese modified Modification of Diet in Renal Disease (CMDRD) equation. RESULTS: In multiple linear regression models, TSH was negatively associated with eGFR after adjusting for confounding factors (ß = -0.072, P = 1.994×10-22). The significance remained in both males and females. No significant association was observed between FT4 and eGFR. In the logistic regression model, we did not observe significant associations of TSH or FT3 with CKD. Participants in the highest quartile of FT4 versus the lowest quartile (reference) had an increased risk of CKD (OR = 1.763, P = 0.012). The risk of CKD was more pronounced in females with the highest quartile of FT4 (OR = 2.424, P = 0.029). CONCLUSION: Our findings suggest that TSH is associated with eGFR in euthyroid individuals and that higher FT4 is associated with an increased risk of CKD. More cohort studies are warranted to confirm whether the association is causal.

Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial.

BACKGROUND: Patients with relapsed/refractory B-cell lymphomas have limited treatment options. GERSHWIN is an open-label, single-arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20+ relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e.g., safety, and efficacy and pharmacodynamics). METHODS: Patients received 1000 mg obinutuzumab intravenously on days 1, 8, and 15 of cycle 1 (CLL patients; first dose split over 2 days), and on day 1 of cycles 2-8. Each cycle lasted for 21 days; the treatment period was 24 weeks. All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety, efficacy, as well as pharmacodynamics. RESULTS: A total of 48 patients (> 18 years of age) were enrolled (CLL: 12; DLBCL: 23; FL: 13). The subjects received a median of two lines of anticancer treatment prior to the enrollment. Thirty-five patients (72.9%) had at least one adverse event (AE). The most frequent AE was infusion-related reactions (15 patients; 31.3%), followed by pyrexia (11 patients; 22.9%). Treatment-related AEs were reported in 28 patients (58.3%), and included one death (interstitial lung disease). End-of-treatment (EoT) response rate was 33.3%. Best overall response rate was 47.9%. Most CLL patients achieved a partial response at EoT (58.3%). CD19+ depletion occurred in 75.0% of the patients with CLL, and all patients with FL and DLBCL. CONCLUSIONS: The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients; no new safety signals were observed. Clinical trial registration ID NCT01680991.

Efficacy, safety and pharmacokinetics of subcutaneous azacitidine in Chinese patients with higher risk myelodysplastic syndromes: Results from a multicenter, single-arm, open-label phase 2 study.

BACKGROUND: Azacitidine safety and efficacy were established in studies of mainly Caucasian patients. Differences in drug metabolism enzymes between Caucasian and East Asian populations prevent extrapolation of drug effects between these groups. This phase 2 study evaluated azacitidine safety, efficacy and pharmacokinetics in patients with higher-risk myelodysplastic syndromes (HR-MDS) in mainland China. METHODS: Patients aged ≥18 years with HR-MDS were to receive subcutaneous azacitidine 75 mg/m2 /day for 7 days per 28-day cycle, for ≥6 cycles. Pharmacokinetic blood samples were collected in cycle 1 predose on days 5-7, and postdose on day 7. Pharmacokinetic outcomes are descriptively compared with those of a historical North American cohort. RESULTS: Of 72 participants, 46 (64%) completed ≥6 cycles. Response rate was 96%, driven primarily by stable disease (94%); one patient achieved complete remission. Hematologic improvement was attained by 53% of patients. Azacitidine mean plasma concentration versus time profiles were similar in shape for Chinese (n = 12) and North American (n = 45) patients. Maximum plasma concentration (Cmax ) was higher in Chinese patients; however, mean azacitidine exposure (1190 ng·h/mL) was similar to the North American cohort (1021 ng·h/mL). Most common grade 3-4 treatment-emergent adverse events (TEAEs) were thrombocytopenia (69%) and neutropenia (67%). CONCLUSIONS: Azacitidine was safe and effective in Chinese patients with HR-MDS. Clinical outcomes were comparable to those for primarily Caucasian patients in the phase 3 AZA-001 study. Cmax differences between Chinese and North American patients were not associated with differences in TEAE frequency or severity. No initial azacitidine dose adjustment is required for Chinese patients with HR-MDS.

Arsenic trioxide at conventional dosage does not aggravate hemorrhage in the first-line treatment of adult acute promyelocytic leukemia.

OBJECTIVES: The arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. METHODS: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP-MS. RESULTS: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 µmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. CONCLUSIONS: In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate.

[Strategy programming for acupuncture development along One-Belt-One-Road countries].

Acupuncture has been applied in 183 countries and regions and gradually become a name card as TCM spreads across the world. The international influence of which plays a significant role in enhancing TCM development. The laws and regulations of TCM acupuncture along One-Belt-One-Road countries were compared and analyzed in this article. With comprehensive research and analysis, the international development strategy of acupuncture was rationally proposed. Combined with the historical background of China's national initiative One-Belt-One-Road, the acupuncture was taken as a breakthrough to lead the global spreading of TCM culture and Chinese herbs, so as to enhance China's soft strength, which could further create a fine cultural environment for the economic prosperity of One-Belt-One-Road countries. In addition, the strategy selection for China regarding TCM acupuncture development along One-Belt-One-Road countries was proposed, and the suggestive solution and implementation strategy for the essential missions and significant issues were provided.

[Clinical Characteristics and Outcome of 66 Cases of Mantle Cell Lymphomas].

OBJECTIVE: To analyze the clinical features and prognostic factors of patients with mantle cell lymphoma(MCL). METHODS: The clinical data of 66 MCL patients were collected from the Department of Hematology of Shanghai Ruijin Hospital, Shanghai Jiaotong University Medical School from January 2000 to December 2014. The clinical characteristics, treatment efficiency and survival rate were analyzed retrospectively. RESULTS: The sex ratio of male to female in these 66 MCL patients was 3.71:1, the nosopoietic median age was 59 years old, and most cases were diagnosed as MCL in Ann Arbor stage III-IV(90.9%). "R-HperCVAD" regimen had the highest CR-rate reached to 55.6%, and CR rate of "R-CHOP" reached to 44.4%. The total prospective 5-year overall survival and progress-free survival rates were 35.5%±11.5% and 8.8%±5.6%, respectively. Leukocyte count abnormality(>10×109/L or <4×109/L), B symptom, LDH level, bone marrow involvement, Ki-67 and high risk group of MIPI scores, and therapy combined with or without rituximab were the independent prognostic factors. CONCLUSION: The prognosis of MCL patients is poor, and the incidence is higher in men. The extranodal sites of bone marrow and gastrointestinal tract are involved more easily. The treatment combined with rituximab can increase survival rate for these patients.

Combination of bortezomib and daunorubicin in the induction of apoptosis in T-cell acute lymphoblastic leukemia.

Despite advances in the treatment of T­cell acute lymphoblastic leukemia (T­ALL), the outcome of T­ALL treatment remains unsatisfactory, therefore, more effective treatment is urgently required. The present study examined the cytotoxicities of bortezomib in combination with daunorubicin against human Jurkat and Molt­4 T­ALL cells and primary T­ALL cells. Compared with treatment alone, co­exposure of cells to bortezomib and daunorubicin resulted in a significant increase in cell death in the Jurkat cells, as evidenced by the increased percentage of Annexin V­positive cells, the formation of apoptotic bodies. In addition, the administration sequence of bortezomib and daunorubicin had an effect on cell viability. Treatment with bortezomib followed by daunorubicin treatment was more effective, compared with treatment with daunorubicin followed by bortezomib. Co-treatment with bortezomib and daunorubicin markedly enhanced the activation of caspase­3, ­8 and ­9, which was reversed by the pan­caspase inhibitor, Z­VAD­FMK. In addition, cotreatment with bortezomib and daunorubicin enhanced the collapse of mitochondrial transmembrane potential and upregulated the proapoptotic protein, B­cell lymphoma 2 (Bcl­2)­interacting mediator of cell death (Bim), but not Bcl­2 or Bcl­extra large. Consistent with this, it was demonstrated that cotreatment of bortezomib and daunorubicin efficiently induced apoptosis in primary T­ALL cells, and cell death was associated with the collapse of mitochondrial transmembrane potential and the upregulation of Bim. Taken together, these findings indicated that the combination of bortezomib and daunorubicin significantly enhanced their apoptosis­inducing effect in T­ALL cells, which may warrant further investigation in preclinical and clinical investigations.

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

PURPOSE: Circularly 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 (CPT + TD) was evaluated in patients with pretreated relapsed/refractory MM (RRMM). METHODS: Patients who received at least two previous therapies for MM were randomly assigned at a 2:1 ratio to receive treatment with CPT + TD 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. RESULTS: Overall, 47 patients were assigned to the CPT + TD group, and 24 patients were recruited to the TD group. The ORR in the CPT + TD group was 38.3 vs. 25.0% in the TD group. The median PFS time was 6.7 months for the CPT + TD group and 3.1 months for the TD group. The median DORs for the CPT + TD and TD groups were 7.1 and 3.2 months, 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. CONCLUSION: CPT 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.

Pharmacokinetics of obinutuzumab in Chinese patients with B-cell lymphomas.

AIM: The Phase Ib GERSHWIN study (NCT01680991) assessed the pharmacokinetic (PK) profile of obinutuzumab following multiple intravenous (i.v.) doses to Chinese patients with B-cell lymphomas, and compared findings with previous obinutuzumab PK studies in mainly Caucasian (non-Chinese) patients. METHODS: GERSHWIN was an open-label, single-arm intervention study. Patients aged >18 years with CD20+ relapsed/refractory chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) were enrolled from four centres in China. The treatment period was 24 weeks; patients received obinutuzumab 1000 mg i.v. on Days (D)1, 8 and 15 of Cycle (C)1 (CLL patients: first infusion split over 2 days) and on D1 of C2-8 (all cycles: 21 days). PK parameters were estimated using non-compartmental analysis (NCA), and a population PK analysis was used to determine whether observed GERSHWIN PK data were in accordance with previous obinutuzumab PK studies in non-Chinese patients. RESULTS: The PK analysis population included 48 patients: 28 patients completed all treatment cycles. NCA showed a similar PK profile in Chinese patients with FL, DLBCL and CLL. Steady-state concentrations of obinutuzumab appeared to be reached at the start of C2 irrespective of histology. There was no apparent relationship between body weight and systemic exposure. Most PK profiles observed in GERSHWIN lay within the 90% prediction interval of simulated profiles. CONCLUSIONS: Obinutuzumab exposure was comparable in CLL, DLBCL and FL patients. NCA and population PK analysis indicate that PK characteristics of Chinese patients with B-cell lymphomas are similar to those in non-Chinese patients.

Clinical observation of caffeic acid in the treatment of thrombocytopenia (CIT) caused by cancer chemotherapy / 中国肿瘤临床

Objective:To evaluate the clinical efficacy and safety of caffeic acid for thrombocytopenia induced by cancer chemothera-py. Methods:A total of 60 patients received the same chemotherapy treatment on cycles 1, 2, and 3. They were given mimetic agent as negative control on the first course. On the second and third cycles, caffeic acid tablets were given from the first day of chemothera-py. Results:The lowest and highest platelet levels of the treatment group during the drug treatment period were significantly higher than those of the negative control group (P<0.001). No significant difference in the period of days of PLT<50×109/L was observed be-tween the groups, although a decreasing trend (P>0.05) was observed. After chemotherapy, the days required for platelet recovery to PLT≥75×109/L and PLT≥100×109/L in the treatment group was significantly fewer than in the negative control group (P<0.001). All the patients did not receive any platelet transfusion during the trial. Conclusion:Caffeic acid tablets were safe and effective for thrombocy-topenia induced by tumor chemotherapy.

Clinical observation of caffeic acid in the treatment of thrombocytopenia (CIT) caused by cancer chemotherapy / 中国肿瘤临床

Objective:To evaluate the clinical efficacy and safety of caffeic acid for thrombocytopenia induced by cancer chemothera-py. Methods:A total of 60 patients received the same chemotherapy treatment on cycles 1, 2, and 3. They were given mimetic agent as negative control on the first course. On the second and third cycles, caffeic acid tablets were given from the first day of chemothera-py. Results:The lowest and highest platelet levels of the treatment group during the drug treatment period were significantly higher than those of the negative control group (P<0.001). No significant difference in the period of days of PLT<50×109/L was observed be-tween the groups, although a decreasing trend (P>0.05) was observed. After chemotherapy, the days required for platelet recovery to PLT≥75×109/L and PLT≥100×109/L in the treatment group was significantly fewer than in the negative control group (P<0.001). All the patients did not receive any platelet transfusion during the trial. Conclusion:Caffeic acid tablets were safe and effective for thrombocy-topenia induced by tumor chemotherapy.