scholarly journals Prognostication of Diffuse Large B-Cell Lymphoma By Lympho2Cx Assay and BCL2 and MYC Expression: Application in a Real Life Context of 154 Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5308-5308
Author(s):  
Stefania Bettelli ◽  
Raffaella Marcheselli ◽  
Samantha Manfredini ◽  
Alessia Bari ◽  
Samantha Pozzi ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Real Life ◽  
B Cell Lymphoma ◽  
Protein Overexpression ◽  
Large B Cell Lymphoma ◽  
Life Context ◽  
Bcl2 Protein ◽  
Nanostring Technology ◽  
Large B Cell

Abstract BACKGROUND: About one third of patients with diffuse large B-cell lymphoma (DLBCL) eventually die from their disease. Thus, it is extremely important to identify powerful and reliable predictive and prognostic markers. In real life patient management, the clinical relevance of the assessment of the Cell of Origin (COO), of MYC and BCL2 protein overexpression, is still not fully clarified. The aim of the study is to evaluate the predictive and prognostic value of COO with Lympho2Cx assay by Nanostring technology and BCL2 and MYC overexpression by immunohistochemistry (IHC), in a real-life context. METHODS: This is a retrospective multicenter study which recruited 154 DLBCL patients treated with R-containing regimen between June 2010 and December 2016 in Modena, Rome (Italy) and Haifa (Israel). All clinical data were recorded at diagnosis and during follow up, including response assessment and survival outcome. COO was determined on formalin-fixed paraffin-embedded diagnostic specimens either by IHC using a panel of antibodies which included CD10, BCL6, MUM1 (i.e. Hans algorithm), or at RNA level with Lymph2Cx assay by Nanostring technology. Expression of MYC and BCL2 was evaluated by IHC. Event free survival (EFS) is defined as the time from diagnosis to the time of last follow-up, or to one of the following events: any response other than complete remission (CR) at the end of therapy or death from any cause. It is assessed by Kaplan-Meier estimates and groups of risk are compared using the log rank test. RESULT: We have currently evaluated the data of 60% (95 out of the 154) of the patients enrolled in the study (Tab 1). After a median follow up of 49 months, EFS is 63% (95CI 51-72%). In univariate analysis, the variables with the greatest impact on the response and on EFS are absolute granulocyte count and BCL2 expression (MYC ongoing). Patients with low IPI showed better survival in comparison with patients with high IPI, but the difference is not statistically significant. By IHC non-GCB subtype was more common than GCB (56% vs. 44%); by Nanostring ABC, GCB and unclassified subtypes were 33%, 50% and 17%, respectively, and K statistics was 0,647, showing a substantial agreement between the results obtained by IHC and by Lympho2Cx assay. No statistically significant differences were observed in EFS among ABC, GCB and unclassified subtypes. However, BCL2 protein overexpression in ABC subtype is associated with shorter EFS. CONCLUSION: Early retrospective studies showed a survival advantage for GCB-type disease. Clinical trial data evaluating the impact of COO determined by GEP on prognosis have shown inconsistent results with 2 studies observing inferior survival of ABC subtype and 2 German studies showing no significant differences in PFS or OS among COO subtypes. Determination of COO by Lympho2Cx is attractive as it is relatively easy and rapid to perform and potentially applicable to clinical practice. However, these preliminary results do not support, at this point, its use as prognostic factor in clinical practice. The analysis of the remaining 59 patients will help to clarify the role Lympho2Cx assay in the context of real life. Table 1. Patients baseline characteristics. Disclosures Tadmor: ABBVIE: Consultancy; ROCHE: Research Funding; JNJ: Consultancy; NOVARTIS: Consultancy; PFIEZER: Consultancy.

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.

scholarly journals Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

2012 ◽  
Vol 30 (28) ◽  
pp. 3452-3459 ◽  
Author(s):  
Nathalie A. Johnson ◽  
Graham W. Slack ◽  
Kerry J. Savage ◽  
Joseph M. Connors ◽  
Susana Ben-Neriah ◽  
...  
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
Molecular Subtype ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Bcl2 Protein ◽  
Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

scholarly journals C-MYC Protein Expression and High Ki-67 Proliferative Index are Predictives of Disease Relapse in Diffuse Large B Cell Lymphoma

2021 ◽  
Vol 6 (1) ◽  
pp. 15-20
Author(s):  
Mahmoud Tag El-Hussien ◽  
Nadia Mokhtar ◽  
Eman Naguib Khorshed
Keyword(s):  
Protein Expression ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Statistical Prediction ◽  
Proliferative Index ◽  
Ki 67 ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Objective: To evaluate the status of C-MYC protein expression and Ki-67 proliferative index and to clarify their role in predicting relapse of diffuse large B cell lymphoma (DLBL). Materials and Methods: A retrospective study conducted on 50 cases diagnosed as DLBL in a 3 years’ time period from January 2014 till December 2016, collected from the archive of Pathology Departments of the National Cancer Institute Cairo - Egypt, Misr University for Science and Technology and private labs of authors. The diagnosis of DLBL for all cases, both nodal and extranodal, was confirmed by histopathologic examination and immunophenotyping. Automated immunohistochemical staining using antibodies against C-MYC protein and MIB-1 was used to evaluate the C-MYC expression in tumor cells and to assess their proliferative ability by calculating Ki-67 labelling index. The relation between the percentage of C-MYC protein expression, Ki-67 proliferative index, clinical data and the relapse status during the follow up period were analyzed. Results: A total of 50 cases of DLBL in both nodal and extra-nodal sites were included. Twenty-three cases (46%) were expressing the C-MYC protein, and 29 cases (58%) showed high Ki-67 proliferative index. Twenty-two cases (44%) relapsed during the follow-up period. Positive C-MYC protein expression was significantly associated with high Ki-67 proliferative index. C-MYC protein expression and high Ki-67 proliferative index were independently associated with disease relapses in 81.8% and 86.4% of cases respectively. Cases with combined C-MYC protein expression and high Ki-67 proliferative index showed statistical prediction of relapse in 81.8% of cases. Conclusion: C-MYC protein expression and high Ki-67 proliferative index were independently associated with relapse of diffuse large B cell lymphoma. Furthermore, the combined positive C-MYC protein expression and high Ki-67 proliferative index is better than a single positive test in predicting relapses among DLBL patients.

scholarly journals Single Centre Retrospective Analysis: Transformation of Waldenström's Macroglobulinemia to Diffuse Large B-Cell Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 11-11
Author(s):  
Bert Heyrman ◽  
Nikki Granacher ◽  
Ka Lung Wu
Keyword(s):  
B Cell ◽  
Retrospective Analysis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Single Centre ◽  
The Past ◽  
Large B Cell Lymphoma ◽  
End Of Treatment ◽  
Large B Cell

Introduction: The incidence and outcome of Waldenström's macroglobulinemia (WM) patients with transformation to diffuse large B-cell lymphoma (DLBCL) are unclear. We performed a retrospective analysis to determine the incidence, clinicopathological characteristics and treatment outcome of WM patient with histologic transformation to DLBCL in our centre. Methods: Single centre chart review of WM patients in the past 10 years. Patients with histologic diagnosis of DLBCL after the diagnosis WM were included in our analysis. Results: Three of the 79 WM patients had histological transformation to DLBCL, two male and one female. Mean age at DLBCL development was 76,6 years. The mean time to transformation since diagnosis of WM was 8,3 years (14, 8 and 3 years). All three patients received at least one prior line of treatment in relation to WM (2, 1 and 3 prior lines). Different regimens used were cyclophosphamide/dexamethasone, rituximab/bendamustin, chlorambucil monotherapy, fludarabine monotherapy, R-CVP and ibrutinib monotherapy. The patients were in clinical CR from WM at the time of transformation, two patients were still on treatment. All three patients presented with advanced disease (stage IIIB, IVB, and IVA) non-GCB subtype DLBCL with at least 2 extra nodal sites. R-IPI scores were 4,5 and 4. Two patients were treated with R-miniCHOP, one patient received R-CHOP. The first patient achieved a CR at the end of treatment and is now 1,5 years in follow-up. The second patient died from pneumonia one year after achieving a CR. The third patient is in follow op since 3 months after reaching a CR at the end of treatment. Conclusion: Over the past decade transformation of WM to DLBCL was 3.7% in our centre. This is in accordance with previous data suggesting an 2.4% risk of transformation over 10 years.Time to transformation varies and no association with prior WM therapy and response to treatment can be found.All patients presented with more aggressive DLBCL in an advanced stage.All three patients achieved a CR following treatment for DLBCL, one patient died from pneumonia, two others are now in follow-up 1,5 years and 3 months respectively. Disclosures Heyrman: Celgene:Research Funding.

scholarly journals Systematic Literature Review of the Clinical Evidence in Relapsed/Refractory (R/R) Large B-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5821-5821
Author(s):  
David G. Maloney ◽  
Fei Fei Liu ◽  
Lisette Nientker ◽  
Cathelijne Alleman ◽  
Brian Hutton ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T ◽  
Large B Cell

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Frontline treatment is curative in ~60% of patients (pts); however, ~30% of pts relapse and ~10% are refractory to frontline treatment. Treatment options for pts with relapsed/refractory (R/R) disease, especially in the third-line or greater (3L+) setting, have been primarily salvage chemotherapies (CTs). Recently, 2 CAR T cell products, axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®), and the antibody-drug conjugate, polatuzumab vedotin (Polivy®), were approved in the 3L setting. A systematic literature review (SLR) of R/R LBCL was conducted to identify relevant evidence on clinical outcomes in LBCL pts, including these new therapies, within the second-line and greater (2L+) or 3L+ setting, and to define the unmet medical need. Methods: This SLR was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and European Union Health Technology Assessment requirements. The review identified randomized and nonrandomized/observational studies within R/R LBCL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma grade 3B (FL3B), primary mediastinal large B-cell lymphoma (PMBCL), DLBCL transformed from indolent lymphomas, and R/R DLBCL with secondary central nervous system (SCNS) involvement. Sources were EMBASE, MEDLINE, The Cochrane Library, and clinical conferences (ASCO, ESMO, EHA, ASH, ICML, AACR, and EORTC) from Jan 2000 to Apr 2019. Results : Following screening of 8683 database records and additional sources, 103 publications covering 78 unique studies were identified. Studies identified were characterized by line of treatment and R/R LBCL subtype (Figure). OS, PFS, DOR, OR, and safety observed from the identified studies were described. Disease subtypes, pt eligibility criteria, and length of follow-up varied notably across studies. In the 3L+ population, 11 salvage CT and 2 CAR T cell therapy studies reported survival outcomes. With salvage CT, the reported ORR across studies ranged from 0% to 54%, while CR ranged from 5.6%-31%. Median OS (mOS) ranged between 3-9 months, with one outlying study reporting mOS at 20 months. Median PFS (mPFS) reported within the salvage CT studies ranged from 2-6 months. Among CAR T cell therapies, pts treated with axicabtagene ciloleucel (n=101) reported a CR rate of 58% and median DOR (mDOR) was 11.1 months after a median follow-up of 27.1 months. mPFS was 5.9 months and mOS was not reached. At a median follow-up of 19.3 months, pts treated with tisagenlecleucel (n=115) had a CR of 40% but the mDOR was not reached. mOS was 11.1 months for all infused patients. In the 2L+ transplant-eligible population (36 studies), pts who received high-dose CT + HSCT achieved mOS between 9 months to 5 years. In the transplant noneligible population, 16 studies reported mOS between 3-20 months. Studies involving mixed transplant-eligible and noneligible populations (30 studies) reported mOS of 1-17 months. A few studies with limited sample sizes were found to report outcomes in LBCL subtypes (eg, PMBCL, SCNS lymphoma, DLBCL transformed from non-FL indolent lymphoma, FL3B). In the 3L+ setting, 1 study reported that mOS was not reached after a median of 6.6 months. In the 2L+ setting, 4 studies reported mPFS and mOS outcomes ranging between 2-9 months and 10-16 months, respectively. Among studies assessing safety of salvage CTs in R/R LBCL, neutropenia, leukocytopenia, thrombocytopenia, and infections were the most commonly reported adverse events (AEs), with neutropenia being the most reported. Among the 3 studies reporting safety outcomes of CAR T cell therapy, data suggest that hematologic AEs (possibly related to lymphodepleting CT), cytokine release syndrome, and neurotoxicity are the most reported. Conclusions : Despite the availability of new therapies for 2L+ and 3L + LBCL, examination of the current evidence has shown that there exists a high unmet need for additional therapeutic options that provide favorable benefit/risk and durable response for these patients. Furthermore, limited data are available for the rarer subtypes of LBCL. Both findings represent important treatment gaps for R/R LBCL that must be addressed in future research geared toward improvement of the current treatment landscape. Disclosures Maloney: Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; BioLine RX, Gilead,Genentech,Novartis: Honoraria; A2 Biotherapeutics: Honoraria, Other: Stock options . Liu:Celgene Corporation: Employment. Nientker:Celgene Corporation: Consultancy; Pharmerit Cöoperatief U.A.: Employment. Alleman:Pharmerit Cöoperatief U.A.: Employment; Celgene Corporation: Consultancy. Garcia:Celgene: Employment, Equity Ownership.

Long-Term Follow-Up of a Phase II Trial of Six Cycles of Dose-Dense R-CHOP-14 for First-Line Treatment of Diffuse Large B-Cell Lymphoma in Young and Elderly Patients

2016 ◽  
Vol 136 (2) ◽  
pp. 76-84 ◽  
Author(s):  
Eva González-Barca ◽  
Miguel A. Canales ◽  
Antonio Salar ◽  
Secundino Ferrer ◽  
Eva Domingo-Domenech ◽  
...  
Keyword(s):  
Survival Rate ◽  
Elderly Patients ◽  
B Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background/Aims: Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) patients. Currently, the standard regimen is R-CHOP every 21 days. Methods: This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged ≥65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2). Results: With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged ≥65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related. Conclusion: In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients.

A case of primary breast diffuse large B cell lymphoma

2021 ◽  
Vol 148 (12) ◽  
pp. 102-107
Author(s):  
Trinh Le Huy ◽  
Tran Dinh Anh
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Excisional Biopsy ◽  
Needle Aspiration ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Painless Mass ◽  
Large B Cell

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin’s lymphoma with limited data. We here report a case of primary breast diffuse large B-cell lymphoma mimicking breast cancer. A 52-year-old woman had a painless mass in her right breast. Fine needle aspiration cytology and core biopsy were performed which suggested malignant features but could not confirm the specific subtype. Excisional biopsy then was conducted revealing non-Hodgkin lymphoma, which was subsequently confirmed with histopathology and diagnosed as diffuse large B-cell lymphoma (DLBCL). A chest computed tomography scan revealed a 3.5 cm sized breast mass with skin thickening and modest lymphadenopathy in the ipsilateral axilla. The patient received six courses of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone plus rituximab) chemotherapy, then whole breast radiation (30Gy in 15 fractions). At 12 months of follow-up, the patient survives with no evidence of disease. No morbidities occurred in this patient during the follow-up period. We briefly review the current practice pattern in patients with primary breast diffuse large B-cell lymphoma.

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