Dongmei Ji

Low incidence of hepatitis B virus reactivation during chemotherapy among diffuse large B-cell lymphoma patients who are HBsAg-negative/HBcAb-positive: a multicenter retrospective study.

Background:u2002 Reactivation of hepatitis B virus (HBV) is less common in lymphoma patients with prior resolved HBV infection [characterized by hepatitis B surface antigen (HBsAg)‐negative/hepatitis B core antibody (HBcAb)‐positive status] compared with chronic HBV infection (HBsAg positive) when receiving chemotherapy alone. The use of rituximab in chemotherapy regimen might increase the risk of HBV reactivation in patients with prior resolved HBV infection. However, the incidence of HBV reactivation is uncertain, and prophylactic antiviral treatment for this group of patients during rituximab‐containing chemotherapy is controversial. The objective of this study was to determine the incidence of HBV reactivation in HBsAg‐negative/HBcAb‐positive patients diagnosed of diffuse large B‐cell lymphoma (DLBCL) and treated with CHOP‐like or RCHOP‐like regimen. In addition, this study also aims to explore the relationship of HBV reactivation and HBV serology.

Recombinant human endostatin in combination with CHOP regimen for peripheral T cell lymphoma.

Peripheral T cell lymphoma (PTCL) has a poor prognosis. Overexpression of vascular endothelial growth factor (VEGF) might contribute to the poor prognosis of PTCL and could be the target of novel therapy. The efficacy and safety of recombinant human endostatin (Endostar) in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (ECHOP) have been explored in 15 PTCL patients. The objective response rate was 80%, with 53.3% patients having achieved complete response (CR) rate. The CR rate was 100% (3/3) in angioimmunoblastic T cell lymphoma (AITL) patients compared to only 36.4% (4/11) in PTCL not otherwise specified (PTCL-NOS) patients. With a median follow-up of 69 months, the 5-year progression-free survival and overall survival (OS) were 53% and 60%, respectively. The 5-year OS was 100% in AITL but was only 45% in PTCL-NOS. Seven out of 11 patients showed overexpression of VEGFR2 in their tumor vessels and had a better efficacy than those with low expression of VEGFR2. Grade 3 or 4 neutropenia is the most common toxicity observed. ECHOP was safe and might display potential benefit in AITL patients.

Phase I Dose‐Escalation Study of Ramucirumab in Chinese Patients with Advanced Solid Tumors

Abstract Lessons Learned. Ramucirumab was well tolerated in Chinese patients with advanced solid tumors, and adverse events were manageable in this study. Pharmacokinetics characteristics in Chinese patients were similar to those in other populations. Immunogenicity was not detected. No efficacy conclusion could be drawn, and further randomized studies are warranted. Background. This single‐arm, nonrandomized, open‐label, dose‐escalation, phase I study was designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of ramucirumab in Chinese patients with advanced solid tumors that were resistant to standard therapy or no standard therapy was available. Methods. Dose escalation was a 3u2009+u20093 design, with expansion in Cohorts 2 and 3 for PK. Ramucirumab was given intravenously at three different dosages: 6 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, and 8 mg/kg every 2 weeks. Safety analyses included all patients. PK, immunogenicity, and antitumor activity were also assessed. Results. Among 28 patients treated, 2 experienced dose‐limiting toxicity, possibly related to ramucirumab. No maximum tolerated dose was determined. All patients experienced at least one treatment‐emergent adverse event. Grade ≥3 adverse event was reported for 53.6% (nu2009=u200915) of patients. PK analyses indicated that ramucirumab had low clearance, small volume of distribution, and long half‐life in Chinese patients, as in other populations. Immunogenicity was not detected. No patient had complete/partial response, and 64.3% (nu2009=u200918) had stable disease with a median duration of 5.55 months (95% confidence interval: 3.38−7.13 months). Conclusion. Ramucirumab appeared to be well tolerated in Chinese patients with advanced solid tumors. PK characteristics in Chinese patients were similar to those in other populations.

Thalidomide enhanced the efficacy of CHOP chemotherapy in the treatment of diffuse large B cell lymphoma: A phase II study

Cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab (R-CHOP) is the standard treatment for patients with diffuse large B cell lymphoma (DLBCL). However, rituximab cannot be popularly applied in a considerable number of patients with DLBCL because of economic reasons. To develop a new regimen to improve the outcome of these patients is extremely important. In our study, sixty five patients with DLBCL were randomly assigned to thalidomide plus CHOP group (n=32) or to CHOP alone group (n=33). Objective response rates (ORR) and complete remission rates (CRR) were 96.7% and 80.6% in T-CHOP group versus 78.9 % and 57.8 % in CHOP group, respectively (P <0.05). At a median follow-up of 96 months, median PFS for T-CHOP group was still not reached yet, and in CHOP group it was 22.9 months (95% CI [0-50.4]). (P=0.163). Median overall survival (OS) for T-CHOP group was also not reached, and the estimated median OS for CHOP group was 83.5 months, the difference of OS between the two groups is not significant (p=0.263). But, in patients with Bcl-2 positive and Bcl-6 negative, the median PFS in T-CHOP group was longer than that in CHOP group (111.0 vs 8.5 months (P=0.017). In addition, thalidomide did not significantly increase the grade 3/4 toxicity of CHOP. We concluded that the addition of thalidomide to the CHOP regimen significantly improved the CRR and showed a trend of improving clinical outcome in patients with DLBCL, especially for patients with Bcl-2 positive and Bcl-6 negative B-cell phenotype, without increased toxicity.

Role of radiotherapy in patients with limited diffuse large B-cell lymphoma of Waldeyer's ring in remission after R-CHOP immunochemotherapy

The standard treatment of waldeyers ring DLBCL remains controversial. This retrospective study was designed to evaluate the role of consolidation radiotherapy (RT) in patients with stage I/II diffuse large B-cell lymphoma (DLBCL) limited in Waldeyers ring (WR). We included 72 patients, 42 were treated with immunochemotherapy alone (CT group) and 30 were treated with immunochemotherapy followed by radiotherapy (CTu2009+u2009RT group). All patients received at least 3 cycles of R-CHOP regimen and achieved complete remission (CR) after immunochemotherapy. After 53 months median follow-up time, the 5-year progression-free survival (PFS) rates in CTu2009+u2009RT group vs. CT group were 93.3% vs. 92.5% (Pu2009=u20090.896), the 5-year overall survival (OS) rates were 96.7% vs. 94.4% (Pu2009=u20090.649). Patients with oropharyngeal primary had relatively better 5-year PFS and OS rates compared to nasopharyngeal primary (PFS: 98.2% vs. 73.3%, pu2009=u20090.001; OS: 100% vs. 79.0%, pu2009<u20090.001). Moreover, the primary site was the only independent prognostic factor for PFS in the multivariate analysis (pu2009=u20090.012, HR 16.858 [95% CI: 1.883-150.933]).

The size and depth of lesions measured by endoscopic ultrasonography are novel prognostic factors of primary gastric diffuse large B-cell lymphoma

Abstract Diffuse large B cell lymphoma is one of the predominant histological subtypes of primary gastric lymphomas. Factors that contribute to precise stratification and guide the treatment of this disease are still not well understood. We analyzed 73 primary gastric diffuse large B cell lymphoma patients retrospectively, and found that patients characterized by late stage, multiple localization, B symptoms, lower serum albumin level and elevated LDH level had a shorter overall survival through Univariate Cox regression analysis. Multivariate Cox regression analysis demonstrated that ALBu2009≤u200935g/L, stagingu2009≥u2009IIE and multiple sites localization were independent adverse prognostic factors. Significantly, in 35 patients who received endoscopy at diagnosis, Kaplan–Meier analyses indicated that patients with large (≥3u2009cm) and deep lesions (≥11u2009mm) had an inferior OS (pu2009=u2009.01 and .039). These findings implicated that tumor size and depth are two indicators of prognosis under ultrasonography. Further randomized studies with large number of cases are needed.

Response-adapted therapy for limited stage diffuse large B-cell lymphoma based on interim PET-CT: preliminary results of a phase 2 study

Abstract Background Limited stage diffuse large B-cell lymphoma is curable with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone) immunochemotherapy. For patients achieving complete response by interim 18F-fluorodeoxyglucose PET-CT, a previous study showed therapy could be safely de-escalated by omitting the subsequent chemotherapy or radiotherapy. We aimed to adapt the therapy on the basis of the response as assessed by the interim PET-CT. Methods We did this phase 2 study in patients with low risk (International Prognostic Index 0–2), limited stage diffuse large B-cell lymphoma. Patients were initially treated with four cycles of R-CHOP. PET-CT scans were done at baseline and after four cycles. Patients with negative PET (Deauville scores 1–2) received two cycles of rituximab monotherapy, unless they had any risk factors (primary mediastinal large B-cell lymphoma, primary extranodal non-Hodgkin lymphoma, and bulky disease). Patients with these risk factors received another two cycles of R-CHOP as routine practice. Patients with partial response received another four cycles of R-CHOP and a repeated PET-CT scan at the end of treatment. Patients with stable and progressive disease were managed by salvage chemotherapy. The primary endpoint was progression-free survival at 3 years. The trial is registered with ClinicalTrials, number NCT0180412 . Findings From December, 2012, to September, 2015, a total of 143 patients were enrolled and we analysed the 129 patients with baseline and interim PET-CT scans for efficacy. By local assessment, 114 PET-CT scans (88%) were reported as negative and 15 (12%) as positive. With a median follow-up time of 28·2 months (range 15·0–47·4), the estimated 3-year progression-free survival was 91%. Patients with negative interim PET-CT scans had a 3-year progression-free survival of 93% compared with 79% for patients with positive results (p=0·062). The estimated 3-year progression-free survival did not differ between patients with nodal and extranodal primaries (92% vs 91%, p=0·978). Interpretation For patients with limited stage diffuse large B-cell lymphoma, the results of interim PET-CT might predict progression-free survival and adapt the subsequent treatment. For complete response patients without risk factors, the extra two cycles of CHOP might be safely omitted without compromising the efficacy, which needs to be confirmed in a randomised study. Funding None.