Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study / 中华医学杂志(英文版)

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.

Clinical analysis of primary gastric diffuse large B-cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical features and prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) and to evaluate the staging system and treatment modality of PG-DLBCL.</p><p><b>METHODS</b>The clinicopathological data of 69 patients with PG-DLBCL were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) were the primary endpoints.</p><p><b>RESULTS</b>The EFS rates at 1, 3, and 5 years were 83.8%, 71.1%, and 69.0%, respectively, with a mean EFS of 91.3 months. The 1-, 3-, and 5-year OS rates were 91.3%, 80.3%, and 72.4%, respectively, with a mean OS of 98.8 months. Univariate analysis revealed that either EFS or OS was significantly prolonged by the following factors (P < 0.05): modified Ann Arbor stage I(E) or II(E1) disease; normal lactate dehydrogenase (LDH) level; normal hemoglobin level; normal albumin level; International Prognostic Index (IPI) of 0 or 1; tumor size < 5 cm; and less depth of invasion. While gender, age, B symptoms at presentation, performance status and treatment modality were not significantly associated with the prognosis (P > 0.05). Cox regression model revealed that only modified Ann Arbor stage and albumin level were independent prognostic factors for EFS and OS.</p><p><b>CONCLUSION</b>The most accurate staging system and the exact role of different therapeutic options for PG-DLBCL are still debated. Further randomized prospective studies with a large number of patients are still needed to establish an optimal management for this disease.</p>

Clinical significance in detection of immunoglobulin heavy chain clonal rearrangement in bone marrow of patients with B cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the feasibility of semi-nested PCR technique for detection of immunoglobulin heavy chain (IgH) clonal rearrangement in bone marrow of B-cell lymphoma patient and to further evaluate its clinicopathological value.</p><p><b>METHODS</b>Gene clonal rearrangement of IgH was detected by semi-nested PCR using primers of FR2 & FR3A in 105 bone marrow samples of patients with B-cell lymphoma. The PCR detection results were compared with the cytomorphology of bone marrow aspiration biopsy. The correlation between PCR detection results and clinicopathological factors were evaluated.</p><p><b>RESULTS</b>Among 105 cases of B-cell lymphoma, bone marrow involvement was detected by PCR technique in 48 cases (45.7%), while only 22 cases (21.0%) were detected by bone marrow cytological analysis. There was a significant difference between two methods (P < 0.05), and the concordance rate was 71.4%. The incidence of bone marrow involvement at the time of initial diagnosis detected by PCR technique was 30.8% for diffuse large B cell lymphoma (DLBCL), 25.0% for follicular lymphoma (FL), and 100.0% for small lymphocytic lymphoma (SLL), respectively. Bone marrow involvement detected by PCR detection correlated with Ann Arbor stage. Rate of clonal IgH gene rearrangement by PCR in early B-cell lymphoma was lower than that in advanced stage B-cell lymphoma patients (P = 0.02). There was no statistically significant difference in efficacy between patients with positive and negative results detected by PCR (P > 0.05). But difference in complete response (CR) rate (23.3% and 46.3%) had significant difference (P = 0.019).</p><p><b>CONCLUSION</b>Semi-nested PCR analysis may be an effective method for detection of abnormalities in bone marrow in patients with B-cell lymphoma and is superior to cytomorphology. The positive rate in patients with advanced Ann Arbor stage is higher than that in patients with early Ann Arbor stage, and patients with PCR negative result have more chances to achieved CR after treatment.</p>

Prognosis of primary non-Hodgkin's lymphoma of the breast / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics and prognosis of primary non-Hodgkin's lymphoma of the breast (PNHLB).</p><p><b>METHODS</b>The characteristics, treatment methods and outcomes of 45 patients with PNHLB were retrospectively analyzed. Chemotherapy including CHOP and CHOP-like regimens was administered in 43 patients, and monoclonal antibody therapy in 6 patients. Furthermore, 19 patients underwent radiotherapy after chemotherapy.</p><p><b>RESULTS</b>Of these 45 patients, 37 patients had diffuse large B cell lymphoma (DLBCL), patients with T cell or mucosa-associated lymphoid tissue (MALT) lymphoma were 4, respectively. Overall response rate of first-line chemotherapy was 90.7%. Median overall survival (OS) and progression-free survival (PFS) of all patients was 6.82 and 4.25 years, respectively. The results of Cox regression model analysis showed that international prognostic index score (IPI) (RR = 5.682, P = 0.002) and Ann Arbor stage (RR = 1.836, P = 0.040) were negative independent prognostic factors for OS. Central nervous system involvement (RR = 1.107, P = 0.005) was a negative independent prognostic factor for PFS.</p><p><b>CONCLUSION</b>The patients with PNHLB have early occurrence in lifespan. Most pathologic type was DLBCL. IPI and Ann Arbor stage are two independent prognostic factors for survival.</p>

Prognostic factors of invasive non-Hodgkin's lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>There is heterogeneity in non-Hodgkin's lymphoma. The purpose of this study is to investigate the prognostic factors of invasive non-Hodgkin's lymphoma.</p><p><b>METHODS</b>From June 2002 to June 2006, 137 patients with invasive non-Hodgkin's lymphoma were treated by regular regimen consisting of radiotherapy and chemotherapy. The clinical data including prognostic factors was analyzed by SPSS 10.0.</p><p><b>RESULTS</b>After treated with chemotherapy and radiotherapy, 35 (25.5%) patients achieved CR, 67 (48.9%) PR, 6 (4.3%) SD, 29 (21.2%) PD, ORR (objective response rate) of this series was 74.5%. The overall 4-year survival rate was 70.8%. The PFS (prognosis free survival) was 42.7%. Multivariate analysis using Cox model indicated that clinical stage III-IV, PS score > or = 2, more than 2 external nodal involvement were closely correlated with overall survival.</p><p><b>CONCLUSION</b>The overall survival of invasive non-Hodgkin's lymphoma treated with present combined therapy regimen has been improved greatly. However, further investigation is still needed for exploring more effective individualized treatment regimen.</p>

Prognostic predictors of nasal NK/T cell lymphoma detected by immunohistochemical staining / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic predictors of nasal NK/T cell lymphoma.</p><p><b>METHODS</b>The clinicopathologic feature data of 61 patients with nasal NK/T cell lymphoma proven by pathological examination from Jan. 1997 to Jan. 2005 were collected. Expression of survivin, CD44, nm23, p53, Ki-67, MDR-1 and CD95 was detected by immunohistochemical staining in 30 patients with available histologic specimens. The correlation between these factors and prognosis were analyzed.</p><p><b>RESULTS</b>In univariate analysis, performance status, LDH level, clinical stage, initial treatment response, CD56, Ki-67 and CD95 were found to be the prognostic factors associated with time to progression (TTP) in nasal NK/T cell lymphoma, while the performance status, B symptoms, LDH level, initial treatment response, Ki-67 and CD95 were demonstrated as prognostic factors related to overall survival. In multivariate analysis, clinical stage, initial treatment response and performance status were independent prognostic factors for TTP, while the latter two factors were independent prognostic factors of overall survival.</p><p><b>CONCLUSION</b>Clinical stage and initial treatment response, and performance status are found to be independent prognostic factors for TTP, whereas the latter two factors are demonstrated as independent prognostic factors of the overall survival. Overexpression of Ki-67 may be an unfavorable prognostic factor, but overexpression of CD95 may be a favorable one.</p>

Experience of gemcitabine plus cisplatin chemotherapy in 52 patients with head and neck cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of combination chemotherapy using gemcitabine plus cisplatin for recurrent and/or metastastic head and neck cancer patients.</p><p><b>METHODS</b>Fifty-two patients with recurrent or metastatic head and neck cancer were treated by gemcitabine 1000 mg/m(2) on D1, 8 and cisplatin 25 mg/m(2) on D1 approximately 3 every 21 days as one cycle.</p><p><b>RESULTS</b>Of 52 assessable patients, 3 (5.8%) showed complete response and 19 (36.5%) partial response with an overall response rate of 42.3% (22/52). Median time to progression was 5.0 months, and 1-year survival was 43.4% with a median survival time of 9.9 months. Of 32 previously treated patients by cisplatin-containing regimen, 2 patients (6.3%) gave complete response and 11 (34.4%) partial response with an overall response rate of 40.6% (13/32). Median time to progression was 3.4 months, and 1-year survival was 29.2% with a median survival time of 8.3 months. Toxicity mainly included grade 1/2 myleosuppression, rash and nausea/vomiting.</p><p><b>CONCLUSION</b>Gemcitabine plus cisplatin chemotherapy is safe and effective for patients with recurrent and/or metastastic head and neck cancer.</p>

Vinorelbine plus cisplatin in the treatment of advanced non-small cell lung cancer previously treated with taxane-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and toxicity of vinorelbine plus cisplatin in the treatment of advanced non-small cell lung cancer (NSCLC) previously treated with taxane-based chemotherapy.</p><p><b>METHODS</b>Thirty patients (0 - 1 score ECOG performance status) with stage IIIB/IV NSCLC previously treated with taxane-based chemotherapy were eligible for the study. Fifteen patients received the regimen of vinorelbine plus cisplatin (NP), the others received mitomycin, vindesine plus cisplatin (MVP).</p><p><b>RESULTS</b>The overall response rates were 13.3% in NP and 0 in MVP (P > 0.05). Time to progression was longer for NP patients than that for MVP ones (6 v 3 months, P < 0.05), so was median survival (9 v 6 months, P < 0.05). The 1-year survival rate of 40.0% in the NP group was significantly higher than that of 0 in MVP (P < 0.05). Grade III-IV toxicity was observed at a similar rate in both groups (P > 0.05), though both well tolerated.</p><p><b>CONCLUSION</b>Regimen of vinorelbine plus cisplatin is appropriate for good performance status patients with advanced non-small cell lung cancer previously treated with taxane-based chemotherapy. Time to progression, median survival and 1-year survival are satisfactory in patients treated with NP, which is complicated with acceptable toxicity.</p>