scholarly journals Combined Plasma Fibrinogen and Neutrophil-Lymphocyte Ratio As a Predictive Factor in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4590-4590
Author(s):  
Liu Yingyue ◽  
Xiangxiang Zhou ◽  
Yurou Chu ◽  
Tiange Lu ◽  
Mei Ding ◽  
...  
Keyword(s):  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Advanced Stage ◽  
Extranodal Involvement ◽  
Neutrophil Lymphocyte Ratio ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: A growing number of epidemiological evidence supports that the coagulation cascade and tumor-associated inflammatory indicators are related to the recurrence and survival of diffuse large B-cell lymphoma (DLBCL). Plasma fibrinogen and neutrophil-lymphocyte ratio (F-NLR) is a novel hallmark that is proposed as an adverse prognosticator in a variety of malignancies. The purpose of this study was to investigate the prognostic impact of the F-NLR score in DLBCL. Methods: In this retrospective study, 231 patients with DLBCL treated between October 2013 to January 2020 at Shandong Provincial Hospital were included. The critical values of fibrinogen and NLR were determined according to receiver operating characteristic (ROC) curve analysis. The included population was stratified into three groups according to the F-NLR score. The prognostic factors associated with progression-free survival (PFS) and overall survival (OS) were screened by multivariate Cox regression analyses and log-rank test. Results: Within the 231 patients analyzed, 55.4% male and 44.6% female were enrolled in this study. There were 138 (59.7%) patients under 60 years old, with mean age of 55.23±15.02 years old. A total of 184 (79.7%) patients had advanced stage (III or IV) disease, and the great majority of people were defined as non-GCB (64.1%) subtypes and had extranodal involvement (86.6%). The cutoff value was identified as 3.12 for NLR (AUC: 0.628), 4.05 g/L for fibrinogen concentrations (AUC: 0.616), and the AUC value was 0.676 for the F-NLR (Fig 1) by OS outcome. The median follow-up period for all patients was 22 months, ranging from 1 to 90 months. After median follow-up time, 101 (43.7%) patients relapsed or progressed and 77 (34.2%) patients died during or after first-line therapy in total. In the further univariate and multivariate analyses, we demonstrated that F-NLR (HR=1.953, 95%CI=1.404-2.717, P=0.000) was an independent prognostic factor of DLBCL survival. We calculated the β for OS value of NLR and fibrinogen according to Cox regression equation. Since the HR for OS of each marker is approximation, we assigned the same weight to each factor in the prognostic scoring model (F-NLR). The model was simplified to 3 groups with F-NLR score of 0: neither hyperfibrinogenemia nor high NLR (low risk; 39.8% of pts), F-NLR score of 1: one of these hematological abnormalities (intermediate risk; 38.5% of pts), or F-NLR score of 2: both hyperfibrinogenemia and high NLR (high risk; 21.7% of pts). As a result, the PFS and OS were significantly worse in DLBCL pts with an F-NLR score of 2 than those with an F-NLR score of 0-1 (P=0.002 Fig 2A, P=0.000 Fig 2B). Moreover, the F-NLR score is significantly associated with clinical outcomes in elderly pts with advanced stage (III or IV) or extranodal involvement through subgroup analysis. Conclusion: This study validates that the F-NLR score, a new inflammation-based grading system, is a promising clinical predictor for DLBCL especially elderly patients with advanced stage (III or IV) or extranodal involvement. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Characteristics and Outcome of Diffuse Large B Cell Lymphoma Among HTLV-1 Carriers in Peru: A Matched Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-39
Author(s):  
Bryan Valcarcel ◽  
Daniel J Enriquez ◽  
Gustavo Sandival-Ampuero ◽  
Ursula Aviles-Perez ◽  
Juan C Haro ◽  
...  
Keyword(s):  
B Cell ◽  
Clinical Features ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common variant of non-Hodgkin lymphoma (NHL) accounting for approximately 30% of the NHL cases worldwide. Previous reports have associated certain viral infections with the development of DLBCL such as HIV and EBV, both infections related with an aggressive clinical course and worse outcome. The human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus regarded as the pathogenic agent for adult T-cell lymphoma/leukemia. HTLV-1 is endemic in Japan, the Caribbean basin, South America, and parts of Africa. In Peru, up to 3% of the healthy adult population carries HTLV-1. As data on the impact of HTLV-1 infection in DLBCL outcomes is scarce, we aim to describe the clinical features and outcomes of HTLV-1-positive patients with a pathological diagnosis of DLBCL. Methods: We retrospectively reviewed medical records of patients diagnosed and managed for DLBCL at the National Institute of Neoplastic Diseases in Lima-Peru between 2007 and 2019. Patients were evaluated for HTLV-1 infection at the time of diagnosis. Positive HTLV-1 cases were matched to negative HTLV-1 controls based on age, sex, and cancer staging. Treatment responses were assessed according to the Lugano criteria. Overall survival (OS) and event-free survival (EFS) curves were estimated using the Kaplan-Meier method and compared with the Log-rank test to determine the impact of HTLV-1 infection. Multivariate Cox regression models were reported with adjusted Hazar Ratios (aHR) with a 95% confidence interval (95% CI). Results: A total of 192 patients with DLBCL were identified and had sufficient data for analysis. Seventy (37%) cases were positive for HTLV-1 infection and 122 (63%) were not. Table 1 summarizes the clinical features and outcomes of DLBCL patients according to HTLV-1 status. Overall, the majority of patients were ≥65 years (59%), had ECOG performance status ≤2 (95%) and were stage III-IV (51%) at diagnosis. One third (n=64) of patients had extranodal involvement with 71 affected sites of which bone marrow involvement was frequently found in HTLV-1-negative DLBCL cases (55% vs. 7%, p<0.001) and liver/gastrointestinal tract in HTLV-1-positive cases (48% vs. 9%, p<0.001). There was no difference among DLBCL groups regarding risk stratification based on NCCN-IPI score (p=0.394). With a median follow-up of 6.5 years, we found that in DLBCL patients, HTLV-1 infection had no significant impact in 5-year OS (HTLV-1-positive 40% versus HTLV-1-negative 42%, p=0.930) and EFS rates (HTLV-1-positive 33% versus HTLV-1-negative 32%; p=0.890) (Figure 1). Multivariate cox regression analysis could not identify HTLV-1 infection as a risk factor for higher mortality or disease progression (Figure 1). Conclusion: To the best of our knowledge, this is the largest case series describing the clinical characteristics and outcome of HTLV-1-positive DLBCL patients. A study from Japan on early stage localized (head and neck) B-cell-NHL (n=198, HTLV-1 seropositive n=21 and with DLBCL n=12) treated with radiotherapy and/or multi-agent chemotherapy found poorer prognosis on HTLV-1 carriers compared to non-carriers (5-year OS: HTLV-1-positive n=21, 49% vs. HTLV-1-negative n=177, 78%, p=0.007; Hiroaki et al BJH 2003). In this study, we included DLBCL patients with both early and advanced stage disease along with localized and extranodal involvement. We found that HTLV-1 infection had no significant impact on 5-year OS and EFS rates when using conventional therapy for DLBCL. Moreover, we did not find differences in relapsed and mortality rates. Further investigation is needed to confirm the potential impact of HTLV-1 infection in DLBCL outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals Risk of Fracture Following Front Line R-CHOP Immunochemotherapy in Older Patients with Diffuse Large B Cell Lymphoma Is Common

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1615-1615
Author(s):  
Stephen Booth ◽  
Hannah Plaschkes ◽  
Amy A Kirkwood ◽  
Adam Gibb ◽  
Patrick Horgan ◽  
...  
Keyword(s):  
B Cell ◽  
Older Patients ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bone Involvement ◽  
Large B Cell Lymphoma ◽  
History Of ◽  
Large B Cell

Introduction Diffuse large B cell lymphoma (DLBCL) and osteoporotic fracture are commoner in older patients (pts). Steroids and chemotherapy are recognised as a risk factor (RF) for fragility-related fracture and its associated morbidity. A small randomised trial (RCT) (Westin 2013) showed bisphosphonates stabilize bone mineral density (including all ages / histologies) in NHL pts. Despite this, there is a lack of data defining the specific incidence and fracture risk in older DLBCL pts post R-CHOP. We aimed to better define this risk in this specific cohort. Methods Data on consecutive DLBCL pts ≥70 years (y) treated with R-CHOP were retrospectively collected across 7 UK centres (2009-2019). Follow up was censored in 07/2019. All pts had untreated, de novo DLBCL or untreated transformed (to DLBCL) indolent B cell NHL. PTLD, HIV and pre-treated NHL pts were excluded. All pts received 1-9 cycles of full or attenuated R-CHOP with curative intent. Pts were excluded if they had progressive disease (PD) or died < 6 months (m) of cycle 1 R-CHOP (RCHOP1). A detailed anonymised database included ECOG performance status (PS), body mass index (BMI), history of osteoporosis / osteopenia, documented steroid pre-phase, vitamin D supplementation, calcium and alkaline phosphatase levels, and sites of bone DLBCL involvement. Fractures at diagnosis (DLBCL-related/unrelated) and pre diagnosis were collected. Fractures (including bone site) occurring during 18m from RCHOP1 were identified from radiology records. Pts were followed for a minimum of 6m and censored at 18m from RCHOP1, or at their last follow up if < 18m or at PD or death if between 6-18m. Baseline pt characteristics were descriptive. Survival analyses were performed using Kaplan Meier methods and Cox regression with comparisons between categories using the log-rank test. Time to event analyses were measured from RCHOP1 until fracture event. Primary end point was 18m cumulative fracture incidence censoring pts at death or relapse. Univariable and multivariable analyses (UVA; MVA) of potential influencing RFs for fracture was assessed by Cox regression (Final stepwise model; p=0.1 for inclusion). Results Of 589 pts identified, 92 pts had PD or died prior to 6m and were excluded. 20 pts were excluded due to short follow up. Across 477 pts, the median age was 77 (range 70-93) y. 66% had an ECOG PS 0-1. The median cycles given was 6 (range 1-9). 27.3% received pre-phase steroids. The median BMI was 25.5 (range 14.2-48.1). 8.1% had a fracture prior to DLBCL, and 9.1% had a history of osteopenia or osteoporosis. 5.7% were current smokers, 3% had rheumatoid arthritis, 13.5% had type (T) 2 diabetes (DM), and 4.5% had a history of excess alcohol. At baseline, 25.2% had PET or CT-assessed cortical bone involvement. Overall, there were 52 fractures, including 50 within 18m follow up. Cumulative fracture incidence was 6.3% (95% confidence interval (CI) 4.4 - 8.9) at 6m, 9.5% (95% CI 7.1 - 12.6) at 12m and 11.5% (95% CI 8.8 - 14.9) at 18m (Fig A). 6 pts had multiple fracture sites (2; n=5, 3; n=1). 32 (62%) had vertebral fracture(s). Thoracic (34% 20/59) and lumbar vertebral (27% 16/59) were dominant sites (Fig C). 7/52 fractures were at the site of DLBCL involvement, 17/52 were at a different site from initial bone DLBCL involvement, 27/52 were in pts without bone involvement and 1/52 was unknown. Univariable RFs included female sex (hazard ratio (HR) 1.89 (95% CI 1.05 - 3.28)), known osteopenia or osteoporosis (HR 2.64 (95% CI 1.32 - 5.29)), DLBCL-related fracture at diagnosis (HR 4.05 (95% CI 2.07 - 7.92) (Fig B). Initial bone involvement was only associated with an increased risk in pts with a DLBCL-related baseline fracture (95% CI HR 4.56 (2.27 - 9.17)) (Table 1). MVA showed that DLBCL-related baseline fracture (HR 4.32 (1.97 - 9.47)) was the only significant independent RF for fracture with low BMI (p=0.051) and smoking history (p=0.052) of borderline significance (Table 2). Conclusions This is the largest series to date to show there is a clinically relevant fracture risk in older DLBCL pts specifically receiving R-CHOP in early follow up. Our data have limitations inherent to a retrospective study including the potential for unknown confounders, missing data, and medical record misinterpretation. Prospective data is required to validate RFs identified which could enable targeting a high-risk population. An RCT is needed to determine the value of prophylactic intervention(s) in high risk pts. Figure Disclosures Gibb: Takeda: Research Funding. Collins:Gilead: Consultancy, Honoraria. Eyre:Janssen: Honoraria; Abbvie: Honoraria; Gilead: Consultancy, Honoraria, Other: commercial research support; Roche: Honoraria.

Intensified 1st Cycle Rituximab (R) Plus 8th Cycles of R-CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) Chemotherapy In Patients with Advanced or Bulky CD20+ Diffuse Large B-Cell Lymphoma (DLBCL); Open-Labelled, Multicenter Phase II CISL Study-Interim Analysis.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1786-1786
Author(s):  
Jin Seok Kim ◽  
Won Seog Kim ◽  
Seok Jin Kim ◽  
Hyeon Seok Eom ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Intermediate Risk ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
Prognostic Group ◽  
Grade 3 ◽  
Large B Cell

Abstract Abstract 1786 Background: Six to Eighth cycles of R-CHOP (Rituximab + cyclophosphamide, adriamycin, vincristine and prednisolone) has been widely used as standard regimen for the advanced stage diffuse large B-cell lymphoma (DLBCL). However, the optimal dose and number of rituximab application have not been determined to date. According to the recent German DENSE-R-CHOP-14 trial, additional use of rituximab (12th dose of rituximab) showed increased complete remission (CR) rate in high risk DLBCL patients. Based upon the promising results of DENSE-R-CHOP-14 chemotherapy in DLBCL, we have been investigated the efficacy and safety of additional 1st cycle Rituximab + 8th cycles of R-CHOP chemotherapy (R+8th R-CHOP, every 3 weeks) in patients with previously untreated stage III/IV or bulky DLBCL. Methods: 92 patients with advanced stage DLBCL (Bulky stage II or Stage III or IV) from 21 institutions received 8th cycles of R-CHOP-21 with additional rituximab on days 0 of 1st cycle between January 2009 and December 2009. The primary endpoint was complete response rate after 3rd cycles of treatment. Among 92 patents who were initially enrolled this study, 14 patients had no response data after 3rd cycles of chemotherapy (3 refuse consent, 2 early death, 7 no evaluation, 1 transfer to other institution, 1 serious toxicity). The DLBCL patients who were treated with 6–8th cycles of R-CHOP-21 will be analyzed for historical control data. The trial is registered on National Cancer Institute website, number NCT01054781. Results: Fifty two patients (56.5%) were older than 60 years (median age; 63); 16 (17.4%) had a poor performance status (ECOG 3 2); 64 (69.6%) had an elevated lactate dehydrogenase (LDH) and 89 (93.5%) had stage III/IV disease. According to the International Prognostic Index (IPI), 5 (5.4%) patients had low risk, 28 (30.4%) had low–intermediate risk, 43 (46.7%) had high–intermediate risk, and 16 (17.4%) had high risk disease. According to the revised IPI, 33 (35.9%) patients had good prognostic group (IPI score 1–2), and 59 (64.1%) patients had poor prognostic group (IPI score 3–5). Among the 78 evaluable DLBCL patients, complete remission (CR) rate was 42.3% (33/78) after 3rd cycles of chemotherapy. Response rate after 3rd cycles of chemotherapy was 96.2% (42.3% CR + 53.8% partial remission). CR were observed in 80% (4/5) of low IPI patients, 65.2% (15/23) of low intermediate IPI, 32.4% (12/37) of high intermediate IPI and 15.3% (2/13) of high IPI (P = 0.087). And CR also observed in 67.9% (19/28) of the patients with good revised IPI and 28% (14/50) of the patients with poor revised IPI (P = 0.007). Infection was one of the most frequent 3 grade 3 adverse events (17/92; 18.5%). Two (2.2%) treatment related deaths (infection) were observed. Other grade 3 and 4 adverse events were occurred as follows; neutropenia (47.8%), anemia (13.1%), thrombocytopenia (5.4%), generalized weakness (6.5%), diarrhea (3.3%), anorexia (2.2%), abdominal pain (2.2%), neuropathy (1.1%) and muscle pain (1.1%). Conclusion: The addition of rituximab on days 0 of 1st cycle of R-CHOP to the standard 8th cycles of R-CHOP-21 for advanced DLBCL showed acceptable response rates after 3rd cycles of chemotherapy and acceptable toxicities. We will evaluate the long-term follow up results and the comparison analysis with historical controls receiving standard R-CHOP-21. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact of Extranodal Diffuse Large B-Cell Lymphoma in the Era of Immunochemotherapy and PET/CT Staging

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1630-1630
Author(s):  
Tarec Christoffer El-Galaly ◽  
Diego Villa ◽  
Musa Alzahrani ◽  
Jakob Werner Hansen ◽  
Laurie H. Sehn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Pet Ct ◽  
Extranodal Disease ◽  
Large B Cell

Abstract Background: Extranodal disease is common in diffuse large B-cell lymphoma (DLBCL), and involvement of more than one extranodal site is associated with a worse outcome. 18F-fluorodeoxyglucose PET/CT (PET/CT) is the current state-of-the-art for staging of DLBCL, and has shown to be much more sensitive for the detection of extranodal involvement than a stand-alone CT scan. Therefore, a re-evaluation of the clinical significance of extranodal disease among PET/CT staged DLBCL patients is warranted. Patients and Methods: We retrospectively included patients from Aalborg (2007-2012), Copenhagen (2009-2012), and British Columbia (2011-2012) in the present study. The inclusion criteria were, i) newly diagnosed DLBCL, ii) R-CHOP or R-CHOP like first-line treatment, and iii) PET/CT staging. The written PET/CT files were reviewed for disease stage and extranodal sites of involvement. The relationship between number of involved sites, extranodal locations and outcome were assessed with simple Cox regression analyses. Extranodal locations with p<0.1 in univariate analysis were entered in a multivariable Cox regression analysis together with the following International Prognostic Index (IPI) factors: age > 60 years, elevated LDH, ECOG performance score >1. Results: A total of 444 patients with a median age of 65 years (range 16-90) and a male:female ratio of 1.3 were included in the study. Of these patients 28% (n=98) had Ann Arbor stage I disease, 16% (n=72) stage II disease, 16% (n=71) stage III disease, and 46% stage IV disease (n= 203). LDH was elevated in 51% (n=224), and 17% (n=74) had ECOG performance status >1. B-symptoms were present in 37% (n=164) and 26% (n=114) had a bulky mass =/> 10 cm. With a median follow-up of 2.4 years (range 0.5-6.5) in patients still alive at the time of analysis, the 3-year OS and PFS were 73% and 69%, respectively. Extranodal disease was diagnosed in 286 (64%) of the patients. The anatomic locations of extranodal disease and their relations to outcome are shown in Table I. Figure 1A and B show the PFS and OS curves when patients are grouped according to the number of involved extranodal sites. Patients with one or two extranodal sites of involvement had similar outcome (3-year PFS 68% vs. 70%), whereas all patients with involvement of more than three extranodal sites progressed. Conclusions: Extranodal involvement is diagnosed in more than half of all newly diagnosed DLBCL patients staged with PET/CT. Bone/bone marrow involvement was the most common site and associated with a worse outcome. Thus, detection of these lesions with PET/CT is clinically important. The presence of extranodal disease is generally associated with a worse outcome, but our data suggest that the optimal cut-off for prognostication in PET/CT staged patients may be more than two sites rather than more than one site, as according to the IPI. Abstract 1630 Table1: Extranodal DLBCL and their relationship with outcome in PET/CT staged patients treated with R-CHOP. Empty boxes represent variables not included in multivariate models. Site Frequency, n (%) HR, univariate HR, multivariate PFS OS PFS OS Lung 33 (7%) 1.56, p=0.002 1.46, p=0.26 Not significant Liver 34 (8%) 2.39, p=0.001 2.43, p=0.002 Not significant Not significant Bone/bone marrow (PET/CT) 127 (29%) 2.49, p<0.001 2.53, p<0.001 1.77, p=0.007 1.66, p=0.03 Bone marrow indolent NHL (biopsy) 28 (6%) 0.86, p=0.70 0.94, p=0.87 Bone marrow DLBCL (biopsy) 43 (10%) 2.55, p<0.001 2.66, p<0.001 Not significant Not significant Gastrointestinal 35 (8%) 1.27, p=0.43 1.02, p=0.96 Kidney 13 (3%) 2.10, p=0.06 1.63, p=0.29 Not significant Soft tissue and muscle 46 (10%) 1.18, p=0.58 1.17, p=0.64 Paranasal sinus 15 (3%) 1.57, p=0.28 1.69, p=0.25 Pleural fluid 16 (4%) 2.82, p=0.005 3.23, p=0.003 2.43, p=0.02 2.53, p=0.02 Testicular 13/252 (5%) 2.42, p=0.22 1.81, p=0.41 Female genitals 10/192 (5%) 3.38, p=0.006 3.76, p=0.003 Figure 1A and B: PFS (Figure 1A) and OS (Figure 1B) in patients grouped according to the number of extranodal sites involved: zero (blue), 1 (green), 2 (grey), 3 (purple), >4 (red). Figure 1A and B:. PFS (Figure 1A) and OS (Figure 1B) in patients grouped according to the number of extranodal sites involved: zero (blue), 1 (green), 2 (grey), 3 (purple), >4 (red). Disclosures No relevant conflicts of interest to declare.

Safety and Efficacy of Rituximab Plus Bendamustine in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3074-3074 ◽  
Author(s):  
Annalisa Arcari ◽  
Annalisa Chiappella ◽  
Vanessa Valenti ◽  
Luca Zanlari ◽  
Monica Tani ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Extranodal Involvement ◽  
Large B Cell Lymphoma ◽  
Stage Disease ◽  
Poor Functional Status ◽  
Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) relapsed or refractory after chemoimmunotherapy have dismal prognosis; the standard salvage treatment is Rituximab plus high dose chemotherapy with autologous stem cell transplantation (R-HDC). However, no standardized treatment is available for patients not eligible for R-HDC because of age and/or comorbidity. The combination Rituximab plus Bendamustine (R-B) has shown to be non-inferior and with a favorable toxicity profile compared to R-CHOP in indolent B-cell lymphoma. The use of R-B in DLBCL is a matter of debate. Purpose: We designed an Italian multicenter retrospective study aimed to evaluate safety and efficacy of R-B as salvage treatment in patients with DLBCL relapsed or refractory after at least one complete course of Rituximab-chemotherapy, who were not eligible for R-HDC because of age and/or comorbidity or in patients with post-HDC recurrence. Patients and Methods: We retrospectively reported 43 unselected consecutive patients with relapsed or refractory DLCBL treated with R-B in 15 Italian haematological centers between October 2008 and January 2014. Schedule of R-B were: 6 courses of Bendamustine at 90 mg/mq or 70 mg/mq on days 1 and 2 of each 28-day cycle and Rituximab 375 mg/mq on day 1 of each cycle. They were analyzed for baseline characteristics (age, IPI, ECOG, comorbidity), outcome (ORR, PFS, OS) and toxicity (CTCAE). Results: The median age was 76 years (range 56-94). Eighty-three % of patients had advanced-stage disease (III-IV stage) and 67% had IPI score of ≥3. An extranodal involvement was present in 65% of cases (bone marrow, lung, stomach, skin, pleura, pericardium). More than half the patients (51%) presented with poor functional status with ECOG score of ≥2. Comorbidity assessment by CIRS-G revelead 30% of patients with ≥1 severely or very severely (level 3 or 4) affected organs and 27% of patients with moderate or severe (level ≥2) cardiopathy. The mean number of prior therapies was 1,7 (range 1-3). All patients were previously treated with Rituximab-chemotherapy and three patients had already received R-HDC. Twelve patients had a refractory disease and 31 experienced relapse after last treatment. Patients received a median of 5 cycles of planned 6 courses of R-B (range 2-6); 24 patients underwent Bendamustine at 90 mg/mq, 19 at 70 mg/mq. All patients received Rituximab 375 mg/mq. In 38% of patients treatment was stopped because of progression; in 4 patients (9%) progression occurred within the first 2 treatment cycles. The overall response rate was 47%, including 28% complete remission and 19% partial remission. One patient in partial remission after R-B achieved a complete remission after local radiotherapy. The median OS was 16 months (95% CI 10-20). The median PFS was 8 months (95% CI 6-11). The median follow up was 10 months (range 2-60). Nine patients are still alive and in complete remission at last follow up; 7 of these patients had a chemosensitive relapse before R-B (in 5 cases a first relapse) and only 2 had a refractory disease with progression after a previous lenalidomide treatment. Toxicity was moderate, mainly grade 1 and 2. Grade 3-4 adverse events were neutropenia in 14 patients (32%), thrombocytopenia in 5 patients (11%), anemia in one patient, infections in 3 patients (6%), skin rash in one patient, nausea in one patient, diarrhea in one patient. One patient died of septic shock after the third R-B cycle. One patient died of miocardial infarction related to underlying cardiac comorbidity. Conclusions: Bendamustine in combination with Rituximab showed promising efficacy results with a low toxicity profile in a poor prognosis population (advanced stage disease and extranodal involvement, high median age, poor functional status, comorbidities), not eligible for R-HDC. The optimal dosage and schedule of Bendamustine and/or combination with novel drugs should be further investigated, in order to improve the duration of response and reduce the rate of early progression. Disclosures Off Label Use: Bendamustine in diffuse large B-cell lymphoma. Marasca:Mundipharma: Honoraria.

scholarly journals Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

2020 ◽  
Vol 38 (2) ◽  
pp. 155-165 ◽  
Author(s):  
Laurie H. Sehn ◽  
Alex F. Herrera ◽  
Christopher R. Flowers ◽  
Manali K. Kamdar ◽  
Andrew McMillan ◽  
...  
Keyword(s):  
B Cell ◽  
Cox Regression ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Antibody Drug Conjugate ◽  
Risk Of Death ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

PURPOSE Patients with transplantation-ineligible relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) fare poorly, with limited treatment options. The antibody-drug conjugate polatuzumab vedotin targets CD79b, a B-cell receptor component. METHODS Safety and efficacy of polatuzumab vedotin with bendamustine and obinutuzumab (pola-BG) was evaluated in a single-arm cohort. Polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) was compared with bendamustine and rituximab (BR) in a randomly assigned cohort of patients with transplantation-ineligible R/R DLBCL (primary end point: independent review committee [IRC] assessed complete response [CR] rate at the end of treatment). Duration of response, progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression methods. RESULTS Pola-BG and pola-BR had a tolerable safety profile. The phase Ib/II pola-BG cohort (n = 27) had a CR rate of 29.6% and a median OS of 10.8 months (median follow-up, 27.0 months). In the randomly assigned cohort (n = 80; 40 per arm), pola-BR patients had a significantly higher IRC-assessed CR rate (40.0% v 17.5%; P = .026) and longer IRC-assessed PFS (median, 9.5 v 3.7 months; hazard ratio [HR], 0.36, 95% CI, 0.21 to 0.63; P < .001) and OS (median, 12.4 v 4.7 months; HR, 0.42; 95% CI, 0.24 to 0.75; P = .002; median follow-up, 22.3 months). Pola-BR patients had higher rates of grade 3-4 neutropenia (46.2% v 33.3%), anemia (28.2% v 17.9%), and thrombocytopenia (41% v 23.1%), but similar grade 3-4 infections (23.1% v 20.5%), versus the BR group. Peripheral neuropathy associated with polatuzumab vedotin (43.6% of patients) was grade 1-2 and resolved in most patients. CONCLUSION Polatuzumab vedotin combined with BR resulted in a significantly higher CR rate and reduced the risk of death by 58% compared with BR in patients with transplantation-ineligible R/R DLBCL.

scholarly journals Long-Term Follow-up of Primary Bone Diffuse Large B-Cell Lymphoma Treated with m NHL-BFM-90

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3025-3025
Author(s):  
Nelly G. Gabeeva ◽  
Eugene E. Zvonkov ◽  
Anna K. Morozova ◽  
Daria A. Koroleva ◽  
Alla M. Kovrigina ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Advanced Stage ◽  
Large Size ◽  
Large B Cell Lymphoma ◽  
Primary Bone ◽  
Large B Cell

Abstract Background: Primary bone lymphoma (PBL) accounts for about 5% of extranodal lymphomas, the most common type are Diffuse Large B-cell Lymphoma (PBL-DLBCL). R-CHOP chemotherapy combined with or no radiation therapy can induce 5-year overall and progression free survival about 63% and 60% for localized-stage and only 41% and 35% for advanced stage and with adverse factors (AF). Due to the rarity of the disease the optimal treatment strategy still remains unknown. Further research is thus needed to increase treatment efficacy for patients with advanced stage PBL-DLBCL and with AF. Aims: To evaluate the efficacy of mNHL-BFM-90 program in adult patients with advanced stage PBL-DLBCL and with AF. Methods: Twenty three previously untreated pts with PBL-DLBCL underwent mNHL-BFM-90 treatment between May 2007 and July 2014; mean age 41 years (range 17-65); age ≥60 years 3 pts (13,6%); M\F=14\9. Tumor stage according to the Ann-Arbor classification: stage I (involvement of 1 bone) - 7 pts (30,4%), II (involvement of regional lymph nodes) - 3 pts (13%), IV (multiple bone involvement) - 13 pts (56,6%); stage >I 16 pts (69,5%). All pts with stage I had large-size tumors (>6sm) with soft tissue contact invasion. LDH elevation was observed in 10 pts (43,5%), B-symptoms in 15 pts (65%), large-size tumors - 20 pts (87%). The most common tumor sites were the skull bones, vertebrae, and femur. All patients received treatment according to the mNHL-BFM-90 intensive program This program was modified in the following way: adriamycin was administered on the 3rd day of course AA at a dose 50 mg/m2; methotrexate was administered on the 1st day of course C at a dose 1.0 g/m2 for 12 hours. All patients underwent from 4 to 6 courses. Twelve (52%) pts received rituximab on day 0 prior to each course of therapy. Five pts received radiotherapy, all pts received intrathecal prophylaxis of central nervous system (CNS) involvement. Results. Complete remissions were achieved in 23 pts (100%). Relapses were observed in three patients in 6, 9 and 40 months after completion of treatment. From 2 pts with early relapse, one was diagnosed as «double-expression lymphoma» (MYC expression >70%, BCL2 >60%), both pts proliferation index Ki-67 accounted 100%. All 3 pts received salvage therapy and died from progression of disease. With a median follow-up of 69 months (range 17-110) both progression-free and overall survival of 23 pts constituted 87%. Grades 3, 4 hematological toxicity was observed in all pts. No deaths related to mNHL-BFM-90 treatment occurred. No second malignancies were observed. Conclusion The mNHL-BFM-90 demonstrated high efficacy and acceptable toxicity in patients with advanced-stage PBL-DLBCL and with AF. Figure Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Retracted article: Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced stage (III/IV) improves the outcome in the rituximab era

Hematology ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 521-525 ◽  
Author(s):  
Agustin Avilès ◽  
Maria-Jesus Nambo ◽  
Angel Calva ◽  
Natividad Neri ◽  
Sergio Cleto ◽  
...  
Keyword(s):  
B Cell ◽  
Adjuvant Radiotherapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Advanced Stage ◽  
Large B Cell Lymphoma ◽  
Retracted Article ◽  
Large B Cell

scholarly journals Primary Extra-Nodal DLBCL of Glands: Our Experiences outside Guidelines of Treatment

Healthcare ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 286
Author(s):  
Antonello Sica ◽  
Mario Santagata ◽  
Caterina Sagnelli ◽  
Piero Rambaldi ◽  
Renato Franco ◽  
...  
Keyword(s):  
Lymph Node ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Tissues ◽  
Clinical Recovery ◽  
Large B Cell Lymphoma ◽  
Thyroid Glands ◽  
Chemotherapy Protocol ◽  
Large B Cell

Lymphomas usually involve lymph nodes and other lymphoid tissues, but sometimes occur in non-lymphoid organs, called extra-nodal sites. Primary diffuse extra-lymph node large B-cell lymphoma (DLBCL) of the thyroid and parotid gland have been observed rarely. According to the most accredited guidelines, primary extra-nodal DLBCL of the parotid and thyroid glands should be treated with three cycles of R-CHOP followed by radiotherapy of the involved site (ISRT). Surgery alone is not enough to treat DLBCL. We describe two unusual cases of primary extra-nodal DLBCL in elderly patients treated exclusively with surgical resection, given the inability to apply chemotherapy. Both patients achieved clinical recovery, which was maintained after a follow-up of more than 18 months, despite not having performed the indicated chemotherapy protocol. The two cases presented here, and a few others reported in the literature, should be considered exceptions to the rule, and do not allow the conclusion that surgery alone might be sufficient for complete remission.

Sign in / Sign up

Export Citation Format

Share Document