scholarly journals Combination of Decitabine and a Modified Regimen of Cisplatin, Cytarabine and Dexamethasone: A Potential Salvage Regimen for Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Treatment Failure

2021 ◽  
Vol 11 ◽  
Author(s):  
Junxia Hu ◽  
Xin Wang ◽  
Fei Chen ◽  
Mengjie Ding ◽  
Meng Dong ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Response Rate ◽  
Complete Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Line Treatment ◽  
Second Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell

ObjectiveThe prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R-DLBCL) after second-line treatment failure is extremely poor. This study prospectively observed the efficacy and safety of decitabine with a modified cisplatin, cytarabine, and dexamethasone (DHAP) regimen in R/R-DLBCL patients who failed second-line treatment.MethodsTwenty-one R/R-DLBCL patients were enrolled and treated with decitabine and a modified DHAP regimen. The primary endpoints were overall response rate (ORR) and safety. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsORR reached 50% (complete response rate, 35%), five patients (25%) had stable disease (SD) with disease control rate (DCR) of 75%. Subgroup analysis revealed patients over fifty years old had a higher complete response rate compared to younger patients (P = 0.005), and relapsed patients had a better complete response rate than refractory patients (P = 0.031). Median PFS was 7 months (95% confidence interval, 5.1-8.9 months). Median OS was not achieved. One-year OS was 59.0% (95% CI, 35.5%-82.5%), and two-year OS was 51.6% (95% confidence interval, 26.9%-76.3%). The main adverse events (AEs) were grade 3/4 hematologic toxicities such as neutropenia (90%), anemia (50%), and thrombocytopenia (70%). Other main non-hematologic AEs were grade 1/2 nausea/vomiting (40%) and infection (50%). No renal toxicity or treatment-related death occurred.ConclusionDecitabine with a modified DHAP regimen can improve the treatment response and prognosis of R/R-DLBCL patients with good tolerance to AEs, suggesting this regimen has potential as a possible new treatment option for R/R-DLBCL patients after second-line treatment failure.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03579082.

The Effect of Adding Rituximab to CHOP-Based Therapy on Clinical Outcomes for Patients In Different Subgroups of DLBCL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4893-4893
Author(s):  
Shenxian Qian ◽  
Daquan Gao ◽  
Pengfei Shi ◽  
Junfeng Tan ◽  
Ling Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Germinal Center ◽  
Response Rate ◽  
Complete Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 4893 The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been shown to improve the outcome in all age groups with newly diagnosed diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in china. A propensity score method was used to compensate for the non-randomized study design. From January 2004 to December 2009, 68 patients were newly diagnosed with DLBCL Using Hans' algorithm based on CD10, BCL-6, and MUM1, the non-germinal center (N-GCB) subgroup 45(66.2%) and germinal center B-cell-like (GCB) 23(33.8%). 32 in the rituximab plus CHOP-based chemotherapy (R+) group, and 36 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (81.1 vs. 68.1%, P < 0.005,); The complete response rate of N-GCB and GCB in the R+ group was78.2% and 82.1%, p>0.05 respectively. The complete response rate of N-GCB and GCB in the R- group was58.2% and 71.3 %, p P < 0.001. The rituximab can overcome poor outcomes for N-GCB subgroup of DLBCL. The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 69.5% for the R- group, P < 0.001. The 2-year overall survival (OS) was 72% in N-GCB Subgroup and 78% in GCB Subgroup for the R+ group, and 48% in N-GCB Subgroup and 68% in GCB Subgroup for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43–0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited N-GCB subgroup patients). IPI also showed significant impact for PFS (hazard ratio 1.72, 95% CI 1.34–2.14 for one score increase, P < 0.001 as well as OS P < 0.001. In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for DLBCL patients, particularly patients N-GCB subgroup of DLBCL. Disclosures: No relevant conflicts of interest to declare.

R-GEM-Lenalidomide versus R-GEM-P as second-line treatment of diffuse large B-cell lymphoma: results of the UK NRCI phase II randomised LEGEND trial

2019 ◽  
Vol 99 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Andrea Kühnl ◽  
Clare Peckitt ◽  
Bijal Patel ◽  
Kirit M. Ardeshna ◽  
Marian P. Macheta ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Second Line ◽  
Large B Cell Lymphoma ◽  
The Uk ◽  
Large B Cell

scholarly journals Decitabine Can Improve the Efficacy of Second-Line Chemotherapy in Relapsed or Refractory Diffuse Llarge B Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5221-5221
Author(s):  
Xudong Zhang ◽  
Junxia Hu ◽  
Qingjiang Chen ◽  
Mingzhi Zhang ◽  
Ken H. Young
Keyword(s):  
B Cell ◽  
Dna Methyltransferase ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Line Treatment ◽  
Second Line ◽  
Second Line Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Line Chemotherapy ◽  
Large B Cell

Objective Diffuse large B cell lymphoma (DLBCL) is a commom and aggressive of non-Hodgkin lymphoma (NHL). The treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is a first-line treatment for diffuse large B-cell lymphoma,approximately 60-70% of patients can achieve cure, however, 30-40% of patients have disease that is either refractory to initial therapy or relapses after standard therapy.Decitabine is a nucleoside analogue and a hypomethylating agent,inhibits DNA methyltransferase ,which has previously been shown to have direct cytotoxic effects and/or affect cellular differentiation and apoptosis.Studies have found that after low-dose decitabinecanenhancethe chemosensitivity of various cancer cells.In addition,the reported that DNA methyltransferase inhibitors (DNMTI) could affect RR-DLBCL growth and overcome chemotherapy resistance.There is no standard second-line treatment for relapsed or refractory diffuse large B cell lymphoma (RR-DLBCL), and the prognosis is poor.This study prospectively observed the efficacy and safety of decitabine combined with second-line chemotherapy (R±DHAP) in the treatment of relapsed or refractory diffuse large B-cell lymphoma. Methods This study was a prospective, one-arm, multi-center clinical trial (registration number: NCT03579082). Eligible petients were age 14 to 65 years whose survival were expected to be more than 3 months and histopathological diagnosis of diffuse large B-cell lymphoma,and had experienced relapse or did not achieve CR with a R-CHOP or R-CHOP-like regimen,which did not receive DHAP treatment before.Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2.Exclusion criteria included CNS involvement,There are any uncontrollable medical conditions (including uncontrolled diabetes, severe heart, lung, liver, kidney dysfunction),patients with severe infections,and patients who had received radiation therapy.15 patients with relapsed or refractory diffuse large B-cell lymphoma were enrolled, 13 patients were evaluated,including 6 males and 7 females with aged between 30-65 years old,the median age of the patients was 50 years old. One cycle every 21 days, decitabine 10 mg/d intravenous infusion d-5~-1; rituximab 375 mg/m2, d0, ivgtt (rituximab can be used or not); cisplatin 100 mg/m2 , divided into d1~3, ivgtt, cytarabine 2g /m2, q12h, d2, ivgtt, dexamethasone 40mg, d1 ~ 4, ivgtt. The recent objective efficacy evaluation was evaluated using the 2017 NCCN guidelines, and the adverse events were ranked according to the NCI 5.0 evaluation criteria. The primary efficacy indicators were overall response rate (ORR) and time to progress (TTP) by imaging evaluation, and observation of adverse events. Results A total of 15 patients were enrolled, 13 patients were evaluated, 1 complete response (CR), 6 partial response (PR), 3 stable disease (SD), The total effective rate (ORR ) was 53.8% and the median disease progression time (TTP) was 2.5 months.The main adverse event in this experiment was myelosuppression. According to clinical observation, the application of Pegylated Recombinant Human Granulocyte Colony Stimulating Factor (PEG-rhG-CSF) for Injection can significantly improve the myelosuppressive state. Conclusion Decitabine can improve the efficacy of second-line chemotherapy in the relapsedand/or refractory diffuse large B-cell lymphoma, and the adverse reactions can be tolerated. Key words decitabine relapsed or refractory diffuse large B-cell lymphoma efficacy Disclosures No relevant conflicts of interest to declare.

Decreased Brain FDG Uptake in Patients with Diffuse Large B Cell Lymphoma (cold brain) Is Associated with High Risk Disease and Predicts Poor Response to R-CHOP Chemotherapy

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1593-1593
Author(s):  
Meghana Raghavendra
Keyword(s):  
Response Rate ◽  
Complete Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Pet Scan ◽  
Chop Chemotherapy ◽  
Fdg Uptake ◽  
Large B Cell Lymphoma ◽  
The Right

Abstract 1593 Background: Decreased 2-deoxy-2-(18F)fluoro-D-glucose (FDG) uptake by brain tissue, (henceforth “cold brain”) has been occasionally described in the literature in patients with bulky solid tumors. There is currently no data describing brain FDG uptake on positron emission tomography (PET) scan in patients with diffuse large B cell lymphoma (DLBCL) and its association with clinical characteristics as well as prognosis. Method: We retrospectively analyzed clinical data from 110 patients with histologically confirmed DLBCL diagnosed between November 1, 2004 and December 31, 2011. Initial staging PET scans prior to treatment were reviewed. Brain FDG uptake on PET scan was analyzed by an expert nuclear radiologist. Qualitative determination of cold versus normal brain activity was made relative to usual distribution and metabolism. Secondarily, a region of interest cursor was placed on the right basal ganglia for a quantitative standard uptake value (SUV) measurement. In cases where measurement of the right basal ganglia was not possible, the cerebellum was used. Patient characteristics were compared using Fisher's exact test. Survival analyses were performed using Kaplan-Meier curves and compared using log-rank test. Cox proportional regression model was used for multivariate analyses. Results: We included 110 patients in the study. Twenty patients (18%) had cold brain by initial PET scan. The cold brain subgroup had a median age of 72.5 years (range, 46 to 85) and 55.0% were males. Cold brain was associated with higher rates of stage III/IV disease (80.0% vs 52.2%; P = 0.026), International Prognostic Index (IPI) score of ≥3 (85.2% vs. 36.7%; P = 0.0001), and > 1 extranodal sites of involvement (50.0% vs. 26.7%; P = 0.059) compared to the non-cold brain subgroup. Among patients who received rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone chemotherapy (R-CHOP), those with cold brain had a lower complete response rate (44.0% vs. 86.0%; P = 0.030), shorter progression-free-survival (PFS) (4.5 months vs. 9.1 months; P = 0.06), but similar overall survival (OS) (47.9 months vs. 58.4 months; P = 0.26). After adjusting for IPI, patients with cold brain seemed to have a shorter PFS compared to those without cold brain, although this was not statistically significant (hazard ratio: 3.13; 95% CI: 8.20-1.22; P = 0.096). Conclusion: In our study, cold brain was a phenomenon frequently observed among patients with newly diagnosed DLBCL. It was associated with higher risk disease, lower complete response rate to R-CHOP chemotherapy, and potentially shorter PFS. Further studies in larger patient population are needed to determine its true prognostic significance. Disclosures: No relevant conflicts of interest to declare.

Lenalidomide In Combination With R-ESHAP (LR-ESHAP) In Patients With Relapsed Or Refractory Diffuse Large B-Cell Lymphoma Candidates To Autologous Stem-Cell Transplantation: A Phase 1b Study From Spanish Group Geltamo

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4391-4391
Author(s):  
Alejandro Martín ◽  
Alba María Redondo ◽  
Armando López-Guillermo ◽  
Antonio Salar ◽  
Eva González-Barca ◽  
...  
Keyword(s):  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Refractory Disease ◽  
Line Treatment ◽  
Hepatic Toxicity ◽  
First Line ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
First Line Treatment

Abstract Background Diffuse large B-cell lymphoma (DLBCL) patients with relapsed or refractory disease after rituximab-containing first-line therapy have a poor outcome with the current salvage regimens. Consequently, new drugs designed to increase the response rate of salvage regimens should be explored (Gisselbrecht et al, J Clin Oncol 2010, 28: 4184-90). We conducted a phase Ib trial (3+3 design) to establish the safety, tolerability and determination of the maximum-tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were also collected as secondary objective. Patients and Methods Eligible patients must be refractory to, or have relapsed following, first-line treatment with rituximab in combination with an anthracycline-containing regimen, and be eligible for autologous stem-cell transplantation (ASCT). Subjects received three cycles of lenalidomide (5, 10 or 15 mg) given on days 1 to 14 of every 21-day cycle, in combination with R-ESHAP salvage chemotherapy at standard doses (rituximab 375 mg/m2 day 1, etoposide 40 mg/m2 days 1-4, cisplatine 25 mg/m2 days 1-4; citarabine 2000 mg/m2 day 5, and methilprednisolone 500 mg days 1-5). Responding patients received BEAM followed by ASCT. Results During the escalating phase, 3 patients had dose-limiting toxicity in the 15 mg cohort: 1 grade 3 angioedema, and 2 mobilization failures. The MTD was therefore established at 10 mg of lenalidomide and this cohort was expanded to further explore the safety and efficacy of LR-ESHAP. A total of 20 patients (3, 13, and 4 in the 5, 10, and 15 mg lenalidomide cohorts, respectively) were enrolled (18 with DLBCL-NOS, and 2 with Burkitt-like lymphoma): 60% male, median age 58 (23–70) years. First-line treatment consisted of R-CHOP or similar in 18 patients and Burkitt’s lymphoma protocols in 2. Disease status at LR-ESHAP was: primary refractory disease in 13 patients (partial response [PR], n=7; and<PR, n=6), and relapsed disease in 7 (3 early and 4 late relapses). IPI was 0-1 in 35%, 2-3 in 40%, and 4-5 in 25%. To date, 16 serious adverse events (SAEs) have been reported, including 5 episodes of febrile neutropenia, 2 pneumonia, 2 sepsis, 1 ionic imbalance, 1 renal toxicity, 1 facial angioedema, 2 thrombosis, and 1 hepatic toxicity, all of them recovered, and there were no treatment-related deaths. Seventeen patients (85%) completed the planned three cycles of treatment (3 without lenalidomide in the third cycle due to significant toxicity) and 1 patient two cycles (due to persistent neutropenia and thrombocytopenia after the second cycle). Two patients discontinued treatment during the first cycle (1 due to angioedema and 1 due to hepatic toxicity). Of the 18 patients with at least one post-baseline tumor assessment, the overall response rate to LR-ESHAP was 77.8% (44.4% complete remission). All 18 patients were successfully mobilized after one (13 patients) or two (5 patients) mobilization procedures, and 14 (70% of the overall series) underwent ASCT according to protocol. Reasons for not performing the transplant were: early progression of lymphoma (n=4), clinical trial discontinuation due to toxicity (n=2). At the time of this analysis, 8 patients had disease progression and 5 patients have died (all of them from lymphoma). With a median follow-up of 7.4 (2.9 to 27.6) months, the estimated 1-year progression-free survival and overall survival were 52% and 72%, respectively. Conclusions LR-ESHAP shows an acceptable safety profile and encouraging activity in rituximab-pretreated relapsed or refractory DLBCL patients. Further investigation with this regimen is warranted. Disclosures: No relevant conflicts of interest to declare.

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