Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

Acquired Immunodeficiency and Malnutrition in Patients Treated with Bi-Weekly CHOP-Based Chemotherapy for Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2443-2443
Author(s):  
Dorte Tholstrup ◽  
Mads Hansen ◽  
Peter De Nully Brown ◽  
Jesper Jurlander
Keyword(s):  
T Cell ◽  
B Cell ◽  
Opportunistic Infections ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Preliminary Evaluation ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract During the recent years CHOP-14/CHOEP-14 in combination with the monoclonal anti-CD20 antibody Rituximab has become the standard choice of treatment for non-localized, poor risk Diffuse Large B-Cell Lymphoma. We, and others, have observed a relative high incidence of opportunistic infections not normally associated with the short neutropenic periods of CHOP-based treatment. We therefore introduced a prospective risk-assessment study in February 2005. The aim of the study is to assess the degree of malnutrition and immunodeficiency that may be associated with bi-weekly regimens. This is a preliminary evaluation of the first 27 patients included. Median age was 60 (31–80), 21 (78%) had CS III/IV disease, 14 (52%) extranodal involvement, 19 (70%) elevated LDH, 9 (33%) a Performance Score ≥2, i.e.13 (48%) presented with IPI 3–5 disease. Furthermore, 7 (26%) had bone marrow involvement, 8 (30%) bulky disease and 17 (63%) B-symptoms. All patients received 6 or 8 cycles of CHOP-14/CHOEP-14, and 15 patients received Rituximab at day 1 of each cycle. Patients were examined four times: 1) before 1st cycle, 2) 14 days after 4th cycle, 3) 14 days after last cycle (i.e. 6th or 8th), and 4) 3 months after treatment. Examination included blood tests, bodyweight and DEXA-scans. 20 patients (74%) had a significant weight loss during treatment. However, 3/4 had regained normal weight three months later. Consistently, DEXA-scans demonstrated a significant reduction in total lean body mass in 12 (44%) patients. P-protein, p-albumin, and selected trace elements were decreased in about 1/4 of patients during treatment. However, most patients had significant declines in T-cell levels during treatment, and interestingly about 1/4 presented with very low T-cell levels at diagnosis. Thus, total CD3-count was low in 7 (26%) patients at diagnosis, and reduced under treatment in 23 (85%). Both CD4- and CD8-count was low in 6 patients at diagnosis, while CD4 was reduced under treatment in 24 and CD8 in 16 patients. Likewise, a significant decrease of IgA, IgM, and IgG subclasses developed during treatment (Table 1). We conclude that patients treated with bi-weekly CHOP-chemotherapy may develop severely decreased levels of T-cells and severe hypogammaglobulinemia, which may be related to an increased incidence of opportunistic infections such as PCP or CMV reactivation.

Addition of R-HMA to R-DA-EPOCH Favourably Changes the Outcome in Patients with Untreated High-Grade Diffuse Large B-Cell Lymphoma: The First Results of Russian Prospective Multicenter Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2708-2708
Author(s):  
Olga A. Gavrilina ◽  
Eugene E. Zvonkov ◽  
Elena N. Parovichnikova ◽  
Vera V. Troitskaya ◽  
Nelly G. Gabeeva ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Young Patients ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Grade ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Approximately 50% of diffuse large B-cell lymphomas (DLBCL) are defined as high-grade by IPI. They are characterized by aggressive course and poor response to standard chemotherapy (CT): 5-years overall survival (OS) rate of less than 30%. R-DA-EPOCH has demonstrated very optimistic results (overall and progression-free survival (PFS) were 90%), but high-risk patients (IPI 3-4) showed only 43% of OS and PFS [1]. The addition of high-dose AraC (12 g/m2) to the upfront therapy of high-risk DLBCL has significantly improved the outcome on Hyper-CVAD/HMA and mNHL-BFM-90 protocols [2, 3]. But high toxicity of these protocols restricts their application. We suggested that addition of courses R-HMA in rotation with R-DA-EPOCH could improve the treatment outcome and decrease toxicity. Aim: To evaluate the efficacy and toxicity of R-DA-EPOCH/R-HMA protocol in patients with untreated high-grade diffuse large B-cell lymphoma. Patients and Methods: 33 untreated DLBCL patients from 4 centers were enrolled in a prospective study between August 2013 - July 2015; stage II-IV; ECOG 0-3; median age 55 years (27-76); age ≥60y/<60y 50%/50%; M/F 60%/40%; IPI: 48% high-intermediate and 52% high risk; 15% with bone marrow involvement. All patients underwent 4-8 courses (2-4 cycles) of chemotherapy: R-DA-EPOCH (standard dose and scheme), R-HMA (R 375 mg/m2 d1, MTX 1000 mg/m2 24 hours d 2, AraC 3000 mg/m2 q 12 hrs d 3-4). For patients older than 60 year dose of R-HMA was reduced (R 375 mg/m2 d1, MTX 500 mg/m2 24 hours d 2, AraC 1000 mg/m2 q 12 hrs d 3-4). In 4 cases of DLBCL with bone marrow involvement BEAM conditioning and autologous stem cell transplantation were applied. Results: The median follow-up is 12 months (4-24). There was no mortality associated with toxicity. The main non-hematological toxicities of R-HMA were infections (mucositis, pneumonia, sepsis, enteropathy) grades 1-2 and 3-4 in 90% and 10%, respectively. Hematological toxicity grade 4 for less than 4 days we observed only after courses R-HMA. Complete remission (CR) was achieved in 29 (88%) patients. In 2 patients we observed progression of the disease after first cycle of chemotherapy, in another 2 cases - partial remission after 2-3 cycles and following progression of disease. In patients older than 60 years with doses reduction in R-HMA failures were absent, except one later relapse after 13 month CR. With a median follow 12 months overall and disease-free survival of 33 patients constituted 90,5% and 74% , respectively. In a group of patients older than 60 years results of therapy seemed to be better than in young patients: OS were 100% vs 85,6% (p=0,1), DFS were 80% vs 74,9% (p=0,2), respectively. So the combination of R-DA-EPOCH/R-HMA may be considered as optimal intensive approach in the older patients. Conclusions: TheR-DA-EPOCH/R-HMA protocol demonstrated acceptable toxicity and high efficacy in patients with high-grade DLBCL. This protocol has shown optimistic results in the elderly patients and it could be recommended for further investigation in that group. Ññûëêè: 1. Salit RB, Fowler DH, Wilson WH, et al. Dose-adjusted EPOCH-rituximab combined with fludarabine provides an effective bridge to reduced-intensity allogeneic hematopoietic stem-cell transplantation in patients with lymphoid malignancies.J Clin Oncol. 2012. 10;30(8):830-6. 2. Oki Y, Westin JR, Vega F, et al. Prospective phase II study of rituximab with alternating cycles of hyper-CVAD and high-dose methotrexate with cytarabine for young patients with high-risk diffuse large B-cell lymphoma. Br J Haematol 2013; 163(5):611-20. 3. Magomedova AU, Kravchenko SK, Kremenetskaia AM, et al. Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma. Ter Arkh. 2011;83(7):5-10. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

Differences in outcomes between patients whose relapse was diagnosed radiologically versus clinically after autologous transplantation for relapsed/refractory diffuse large B-cell lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19001-e19001
Author(s):  
Ghulam Rehman Mohyuddin ◽  
Ashley Elizabeth Clark ◽  
Leyla Osman Shune ◽  
Tara L. Lin ◽  
Sunil H. Abhyankar ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Clinical History ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Clinical Cohort ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e19001 Background: Surveillance scans performed after autologous stem cell transplant (AutoSCT) for patients with relapsed/refractory (RR) diffuse large B Cell lymphoma (DLBCL) have no proven survival benefit. We studied survival differences among patients with RR DLBCL post AutoSCT whose recurrences were detected on clinical history and exam, versus those detected on routine surveillance scan. Methods: We retrospectively identified 139 patients from our institutional database with DLBCL who underwent AutoSCT from 2000 to 2014. All patients had surveillance scans performed at days 100, 180 and at 1-year post AutoSCT. Results: Among the 139 patients with RR DLBCL that underwent AutoSCT, 37 relapsed, of which 21 were clinical and 16 radiological. There were no statistically significant differences in patient characteristics, although more patients in the clinical cohort had extra-nodal and bulky disease (Table 1). The median time to progression was 167 days for the clinical cohort and 565 days for the radiological cohort (p= 0.03). Median follow-up was 587 days for the clinical cohort and 1503 days for the radiological cohort (p=0.002). Median overall survival (OS) was 587 days for the clinical cohort, and was not reached for the radiological cohort (p=0.006). Conclusions: In our review, most patients with relapsed DLBCL after AutoSCT were diagnosed clinically. Patients whose relapse was diagnosed clinically were likely to be detected earlier and have a shorter OS. Our data indicates that patients with aggressive disease may be detected when clinically relevant, regardless of scanning. Given the known risks of excess radiation exposure, our data suggests that routine scanning may not be necessary in the majority of patients with DLBCL following AutoSCT. [Table: see text]

Retrospective analysis of CD5-positive diffuse large B-cell lymphoma (CD5+ DLBCL) treated with chemotherapy with or without rituximab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8551-8551
Author(s):  
K. Miyazaki ◽  
M. Yamaguchi ◽  
R. Suzuki ◽  
N. Niitsu ◽  
D. Ennishi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Elevated Serum ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Significant Difference ◽  
Large B Cell

8551 Background: CD5+ DLBCL comprises 5–10% of DLBCL, and shows a high incidence of central nervous system (CNS) relapse. It has been included in the 4th WHO classification as an immunohistochemical subgroup. To clarify the prognosis and incidence of CNS relapse of CD5+ DLBCL in the rituximab-era, we conducted a multicenter retrospective study. Methods: We analyzed 313 patients (pts) with CD5+ DLBCL who received chemotherapy with (n=164) or without rituximab (n=149). The current series includes 107 out of 120 pts described in our previous study (Haematologica, 2008). Intravascular large B-cell lymphoma, primary CNS DLBCL, and secondary CD5+ DLBCL were excluded from the study population. Results: 313 pts showed the following clinical features: median age, 67 (range: 15–93); M:F=163:150; elevated serum LDH level, 71%; stage III/IV, 64%; IPI HI/H, 53%. No significant difference in clinical background such as the IPI and its five components, B symptom, male sex, and bone marrow involvement was found between pts who were treated with and without rituximab. Pts treated without rituximab received more dose-intensive chemotherapies (CHOP14, third-generation regimen, and high dose cytarabine-based regimen) than those treated with rituximab (24% vs. 7%, P<0.0001). The CR rate was higher in pts received rituximab than those without (81% vs. 65%; P=0.0014). The median follow-up was 28 months in pts who received rituximab (range: 7–77) and 68 months in those who did not (range: 6–187). Overall survival (OS) was significantly superior for pts with rituximab than for those without (2-yr OS: 68% vs. 54%, P=0.003). Multivariate analysis revealed that the use of rituximab was favorably associated with OS (HR=1.81, 95% CI: 1.26–2.58, P=0.001), but dose-intensive chemotherapies did not affect OS. However, the incidence of CNS relapse was not different between the two groups (2-yr CNS relapse rate: 11.9% vs. 11.4%, P=0.91). 16 of the 20 pts (80%) with CNS relapse in the rituximab group had brain parenchymal disease. Conclusions: Our data show that rituximab improves OS of pts with CD5+ DLBCL, but does not prevent CNS relapse. Future prospective studies to decrease CNS disease for CD5+ DLBCL are warranted. No significant financial relationships to disclose.

Sunitinib in Relapsed or Refractory Diffuse Large B Cell Lymphoma: Results of a Phase II Multi-Center Study of the NCIC Clinical Trials Group.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2729-2729
Author(s):  
Rena Buckstein ◽  
John Kuruvilla ◽  
Neil Chua ◽  
Christina Lee ◽  
David A Macdonald ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
High Dose ◽  
Cell Transplant ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2729 Poster Board II-705 Background: There are limited effective treatment options for patients with diffuse large B cell lymphoma who relapse post autologous stem cell transplant or are transplant-ineligible. The detection of vascular endothelial growth factor (VEGF )A, B and C isoforms and their receptors on many large cell lymphoma samples suggests that the VEGF pathway is critically important and may contribute to disease progression. Sunitinib maleate, is an orally bioavailable inhibitor of VEGF receptor-1 (VEGFR-1), -2, and -3, PDGFR-α and β as well as KIT, FLT3, RET and CSF-1 (Chow, LQ JCO 2007). We tested the efficacy, safety and biomarker activity of sunitinib in patients with relapsed diffuse large B cell lymphoma in a multi-center prospective phase II study. Methods: Eligibility included age 18 or older, histologically confirmed relapsed or refractory diffuse large B-cell (DLBCL), primary mediastinal (PMBCL), or transformed indolent lymphoma, at least one and no more than 2 prior chemotherapy regimens (one anthracycline-containing). The primary endpoint was objective response defined by 1999 Cheson criteria. The secondary endpoints were progression-free and overall survival, toxicity and the effect of sunitinib on peripheral blood circulating endothelial cells (CECs) and their precursors (CEPs). Patients self administered sunitinib 37.5 mg po daily with no breaks in 4 week cycles for up to 1 year. CT imaging was performed every 2 cycles and CEC/CEP assays were done at baseline, day 1 of cycles 2, 3 then q 3 months thereafter. A Simon 2-stage design was used with at least 1 response needed after 15 evaluable patients to complete a planned accrual of 25 patients total. Results: Between Feb 2007 and September 2008 we enrolled 19 patients at 7 Canadian sites - 17 were eligible and are evaluable for toxicity and 15 are evaluable for response. The median age was 65 and patients were a median of 20.3 months(m) from diagnosis (range 5.8–132 m). Fourteen (82%) had a diagnosis of DLBCL, 10 (58%) had responded to their preceding line of chemotherapy - 5 (29%) had relapsed post high dose chemotherapy. The median number of cycles of sunitinib received was 2 (1–5) with only 5 patients remaining on drug for 3 or more cycles. Only 35% of patients received > 90% planned dose intensity with 14 patients missing doses and 5 undergoing dose reductions necessitated by toxicities. Hematological toxicity (grade 3 neutropenia in 5 pts, grades 3–4 thrombocytopenia in 6 pts) and was the most common reason for dose omission. Of the 15 evaluable pts, no objective responses were seen, and 9 achieved stable disease (median duration 3.4 m); and 6 had primary progressive disease. As a result, the study was closed at the end of the first stage. With limited serial sampling, there was no discernable relationship between the change in absolute or apoptotic CEC over time with clinical response as measured by best response or change in bi-dimensional measurements. Conclusions: Sunitinib 37.5 mg po daily showed no evidence of anti-tumour activity in relapsed/refractory large B cell lymphoma and is associated with greater than expected hematological toxicity. Disclosures: Buckstein: Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Off Label Use: It is being tested in NHL.

Clinicopathologic features and outcome of extra-nodal diffuse large B-cell lymphoma: An institutional experience from North India.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20079-e20079
Author(s):  
Sukesh C Nair ◽  
Ajay Gogia ◽  
Lalit Kumar ◽  
Atul Sharma ◽  
Ahitagni Biswas ◽  
...  
Keyword(s):  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Extranodal Involvement ◽  
Bulky Disease ◽  
Female Ratio ◽  
Large B Cell Lymphoma ◽  
Large B Cell

e20079 Background: Primary extranodal diffuse large B cell lymphoma (DLBCL) forms upto 40-50% of all cases of DLBCL . Clinicopathological features and outcome of extranodal DLBCL patients especially in the rituximab era are scarce from developing countries. Methods: We carried out an ambispective analysis of newly diagnosed DLBCL patients (n = 417) over a period of 5 years (2014-2018).Of this total cohort 224 (53.7%) were found to have primary or predominant extranodal involvement. Prognostic factors were identified using Cox-regression analyses. Results: Median age was 50 years (18-86) with male female ratio of 2:1. B symptoms were seen in 48% patients and bulky disease in 39%. ECOG performance status of 0 or 1 was present in 50% and 63% presented with advanced disease. Bone was the most common site of extranodal involvement (32%) in our study followed by gastrointestinal tract ( 30%).Cell of origin (based on Hans algorithm) was available in 80% patients with Germinal center subtype (GCB) forming 44% and non-GCB forming 36% of all patients. Bone marrow involvement was present in 13 % patients. Low risk International Prognostic Index (IPI) was seen in 32 % and 41% were having intermediate risk IPI, the remaining being high risk. CHOP based treatment was used in 80 % of cases and rituximab was used in 76% of all cases. The overall response rate was 76% with a complete response rate (CR) of 65.5%. Presence of B-symptoms, central nervous system (CNS) involvement, non R-CHOP regimen and non-radiotherapy treatment protocols were associated with inferior CR rate. After a median follow up of 26 months, the 3-year event free survival and overall survival were 65 % and 82.7 % respectively. Involvement of specific extranodal sites (kidney, adrenals and CNS), high IPI score and use of non R-CHOP regimens were associated with poor EFS and OS on multivariate analysis Conclusions: This is one of the largest studies from India on extranodal DLBCL in the rituximab era. Involvement of specific extranodal sites, high IPI score and use of non R-CHOP regimens were associated with inferior survival.

scholarly journals The role of pembrolizumab in relapsed/refractory primary mediastinal large B-cell lymphoma

2019 ◽  
Vol 10 ◽  
pp. 204062071984159 ◽  
Author(s):  
Sarah Tomassetti ◽  
Robert Chen ◽  
Savita Dandapani
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
High Dose ◽  
Cell Transplant ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Primary mediastinal large B-cell lymphoma (PMBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL). PMBCL comprises approximately 10% of DLBCLs, thus making it a rare variant of DLBCL. Cure rates for PMBCL with upfront regimens like DA-REPOCH exceed 90%. However, if there is a poor response to this first-line therapy, relapsed/refractory PMBCL (rrPMBCL) has limited treatment options. The historic trend is to treat rrPMBCL with salvage regimens commonly used for DLBCL followed by high-dose therapy and autologous stem cell transplant (HDT-ASCT); however, response rates to salvage therapy remain low and few patients are able to proceed to transplant. An interesting feature of PMBCL is that even though it is classified as a subtype of DLBCL, PMBCL actually shares many clinical, pathologic, and genetic features with classical Hodgkin lymphoma (cHL). For example, both frequently express program death ligand 1 and 2 (PD-L1/2), which is not seen in other mature B-cell lymphomas. The expression of PD-L1/2 in PMBCL makes PDL1 inhibitors, such as pembrolizumab, an attractive therapeutic target. Pembrolizumab is an effective and well-tolerated therapy now approved for a number of cancer types from advanced melanoma to relapsed/refractory cHL. There are now multi-institutional trials underway assessing the role of pembrolizumab in the treatment of rrPMBCL.

A New Simplified Prognostic Index with Age Cut-off of 70 Years for Patients with Diffuse Large B-Cell Lymphoma. A Population-Based Analysis From the Danish Lymphoma Registry, LYFO

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3651-3651
Author(s):  
Anne Ortved Gang ◽  
Michael Pedersen ◽  
Francesco d'Amore ◽  
Lars Møller-Pedersen ◽  
Bo Amdi Pedersen ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 3651 Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma accounting for 35–40%. Since the 1990s, The International Prognostic Index (IPI) has served as useful tool in daily treatment decision algorithm and in the design of clinical trials. In the last decade, improvement of overall survival (OS) has been demonstrated with R-CHOP-like regimens. In addition, the median life expectancy has increased substantially since the 1980'ies and more intensive treatment options like autologous BMT are performed successful up to 70 years of age. Thus, prognostic factors, including age, are susceptible to change over time. Material and methods: Patients with DLBCL diagnosed in the period 2000–2010 treated with Rituximab and CHOP-like chemotherapy were extracted from the Danish population-based Lymphoma Registry that covers > 97% of Danish lymphoma patients. Clinical and laboratory data at time of diagnosis were analysed, leaving out factors with < 75% completeness. Patients with transformed lymphoma, CNS involvement and HIV+ patients were excluded from the analysis. Results: 1990 patients (M:F ratio 1.26) were extracted from the LYFO database. The median age was 65 years, median follow-up was 54 months. Overall median survival was 9.7 years, with a 5 year OS of 65%. Analysis of age using 60, 65, 70, 75 years as cut-off, revealed 70 years as the optimal cut-point. Univariate analysis was performed including age, gender, stage, performance status, extranodal disease, LDH, albumin, immunoglobulin G, bulky disease, lymphocytes and haemoglobin. Only significant factors were included in a Cox proportional hazards model. Results for the entire patient cohort are shown in table I, and for patients <= 70 years in Table II. Survival analysis of patients with 0–1, 2–3 and 4–6 risk factors showed 5-year survival values of 90%, 71% and 45% respectively (left figure). For patients <= 70 years, the corresponding values were 90%, 81% and 62%, respectively (right figure). Conclusion: Two decades after the introduction of the IPI, age, performance status and LDH are still some of the most powerful prognostic factors in DLBCL. Age cut-off at 70 years is meaningful in reflecting clinical practice and, in our analysis, albumin and IgG added significant prognostic importance. In addition, for patients younger than 70 years, male gender is an adverse prognostic factor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

scholarly journals Diffuse large B-cell lymphoma: R-CHOP failure—what to do?

Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 366-378 ◽  
Author(s):  
Bertrand Coiffier ◽  
Clémentine Sarkozy
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Unmet Need ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Disease Stage ◽  
High Dose ◽  
Good Definition ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ∼30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary refractory disease (progress during or right after treatment) whereas 30% relapse after achieving complete remission (CR). Currently, there is no good definition enabling us to identify these 2 groups upon diagnosis. Most of the refractory patients exhibit double-hit lymphoma (MYC-BCL2 rearrangement) or double-protein-expression lymphoma (MYC-BCL2 hyperexpression) which have a more aggressive clinical picture. New strategies are currently being explored to obtain better CR rates and fewer relapses. Although young relapsing patients are treated with high-dose therapy followed by autologous transplant, there is an unmet need for better salvage regimens in this setting. To prevent relapse, maintenance therapy with immunomodulatory agents such as lenalidomide is currently undergoing investigation. New drugs will most likely be introduced over the next few years and will probably be different for relapsing and refractory patients.

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