The Impact on Survival of EBV Positive Diffuse Large B- Cell Lymphoma, Not Otherwise Specified in Young Adults

Abstract Introduction: Epstein Barr virus-positive (EBV+) diffuse large B- cell lymphoma (DLBCL), not otherwise specified (NOS) is a new entity recognized by the WHO 2016. This entity was widely studied in older age patients, but in recent years there are few reports that show that EBV positive DLBCL, NOS can affect younger adults and there is a lack of evidence in this age group. The aim of this study is to evaluate the impact on survival in EBV+ DLBCL, NOS in young adults. Methods: The study was retrospective, reviewing clinical records of patients treated at Rebagliati Martins Hospital between years 2002 - 2013. Patients of both sexes ≥ 18 years old, but ≤ 50 years old, with the diagnosis of EBV+DLBCL, NOS were included. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists at our institution to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. Overall survival (OS) was determinate according to the Kaplan -Meier method, the comparison of the survival curves were made with the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted to evaluate hazard ratios (HR) for OS. Results: A total of 57 patients with a diagnosis of EBV+DLBCL, NOS were included in this analysis. The median age at diagnosis was 43 years (range 25-50 years), 61 % of patients were older than 40 years old and there was a slight female predominance (51%). Clinically, 55% presented ECOG >1, 57% had B symptoms, 68% had an extranodal disease as a primary tumor, 50% had stage III/IV and 26% had ≥ 1 extranodal site involved. EBV positivity was present in 16% of patients (9 patients). PDL-1 expression was present in 12% of patients. 92% received first-line treatment, but 7% of patients did not for progressive disease and death at diagnosis. During the treatment, 92% of patients received R-CHOP and 8% received other regimens. The overall response rate was 71%; 63% had a complete response and 7% had a partial response. The 5-year OS rate was 59%. In the univariate analysis, EBV positivity (<0.001) and ≥ 1 extranodal site involved (p=0.011) were associated with a poor prognosis. In the multivariate analysis, patients with EBV positive had a worse outcome (HR 7.8, 95% 2.2-25.9.2; p=0.001). Conclusions: The prevalence of EBV in young adults with DLBCL is high compared with other series and there is an adverse impact on overall survival in this group of patients. Figure. Figure. Disclosures Castillo: Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Beigene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.

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The Impact of Activated Akt Expression On Clinical Outcome in Diffuse Large B-Cell Lymphoma: A Clinicopathological Study of 99 Cases.

Blood ◽

10.1182/blood.v120.21.2676.2676 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2676-2676

Author(s):

Jung Yong Hong ◽

Moon Ki Choi ◽

Young Saing Kim ◽

Chi Hoon Maeng ◽

Su Jin Lee ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Clinical Impact ◽

Free Survival ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Abstract Abstract 2676 Purpose Akt is a serine/threonine kinase that plays a central role in cell proliferation and growth. To define clinical impact of Akt expression in diffuse large B-cell lymphoma(DLBCL), we investigated the expression of phospho-Akt(p-Akt) in DLBCL and analyzed clinical impact of p-Akt expression on patient survival. Methods We evaluated the p-Akt expression in 99 DLBCL patients using tissue microarray(TMA) technology. Results Positive p-Akt expression was observed in 15.2% of the patients and significantly associated with elevated lactic dehydrogenase level (P = .044). Kaplan-Meier survival analysis showed that the patients with positive p-Akt expression showed substantially poorer overall survival (p-Akt+ vs p-Akt- 25.3 months [95% confidence interval(CI), 14.4–36.2 months] vs 192.6 months [95% CI, 131.3–253.9 months], P < .001) and progression-free survival (p-Akt+ vs p-Akt- 13.6 months[95% CI, 14.4–36.2 months] vs 134.5 months [95% CI, 131.3–253.9 months], P < .001), respectively. Multivariate Cox regression analysis revealed that patients with DLBCL with p-Akt positivity showed poorer overall survival with 3.2 fold (95% CI, 1.6–6.8, P = .002) risk for death compared to patients with DLBCL with p-Akt negativity. Conclusion Positive expression of p-Akt in DLBCL patients is associated with poorer overall and progression-free survival. Expression of p-Akt may act as an independent poor prognostic factor and might be a novel therapeutic target for DLBCL. Disclosures: No relevant conflicts of interest to declare.

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The Neutrophil-to-Lymphocyte Ratio Is Prognostic in Patients with Diffuse Large B-Cell Lymphoma: A Study from the Latin American Group of Lymphomas (GELL)

Blood ◽

10.1182/blood-2018-99-113246 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2987-2987

Author(s):

Brady E. Beltrán ◽

Victoria Otero ◽

Marialejandra Torres Viera ◽

Camila Peña ◽

Myriam Lucía Rodriguez ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factor ◽

B Cell ◽

Latin American ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Entire Group ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Introduction: Diffuse large B-Cell Lymphoma (DLBCL) is the most frequent subtype of lymphoma in the world. The IPI score is a powerful risk-stratification tool in patients with DLBCL. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with DLBCL in Asia, Europe and USA. The GELL is a recently formed group for the study of lymphomas in Latin America composed by large institutions from eleven countries. The aim of this study was to evaluate whether the NLR is a prognostic factor in Latin American patients with DLBCL. Methods: We included patients with a pathological diagnosis of DLBCL who were diagnosed and treated at our institution between 2012-2013. IRB approval was obtained prior to research, and pathological samples were reviewed by hematopathologists at each of the participating institutions to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. The NLR was calculated by dividing the absolute neutrophil by the absolute lymphocyte count and dichotomized in NLR≥4 and NLR<4. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate Cox models were fitted to evaluate hazard ratios (HR) for overall survival (OS). Results: A total of 329 patients with a diagnosis of DLBCL were included in this analysis. The median age at diagnosis was 64 years (range 18-83 years) with a slight female predominance (54%). Clinically, 59% of patients were 60 or older, 34% had ECOG >1, 29% had elevated LDH, and 70% had extranodal disease; 49% had early stage and 51% had stage III and IV. The IPI score was low risk in 36%, low-intermediate in 25%, high intermediate in 22% and high risk in 17%. 41% of patients had NLR ≥4. 89% of patients received standard R-CHOP, 2% received R-miniCHOP and 9% received other regimens. The overall response rate as 83%; 69% had complete response and 14% had partial response. The median follow-up for the entire group was 5 years (95% CI 4.9-5.4 years). The 5-year overall survival (OS) rate for the entire group was 65%. The 5-year OS rates for patients with NLR ≥4 and <4 were 59% and 71%, respectively (p=0.008). Patients with low, low-intermediate, high-intermediate and high IPI scores had 5-year OS rates of 80%, 65%, 56% and 45%, respectively (p<0.001). In the multivariate analysis, advanced stage (HR 3.1, 95% CI 1.9-5.0; p<0.001), LDH level (HR 2.2, 95% CI 1.2-4.2; p=0.016) and NLR ≥4 (HR 1.7, 95% CI 1.1-2.6; p=0.03) were statistically independent factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for IPI score (HR 1.7, 95% CI 1.1-2.6; p=0.01). Conclusion: The NLR appears as a novel and easy to use prognostic factor for OS, independent of the IPI score, in previously untreated Latin American patients with DLBCL. Our findings support the need for validation of the NLR in larger retrospective or prospective studies in patients with DLBCL. Figure. Figure. Disclosures Chiattone: Janssen: Honoraria, Research Funding. Castillo:Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Genentech: Consultancy.

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Rituximab Does Not Improve Progression Free (PFS) or Overall Survival (OS) in Patients with Limited Stage Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v114.22.3755.3755 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3755-3755

Author(s):

Ephraim P. Hochberg ◽

Nicole Birrer ◽

Christiana E. Toomey ◽

Jeffrey A. Barnes ◽

Alfred Ian Lee ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Newly Diagnosed ◽

Logrank Test ◽

Limited Stage ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Abstract Abstract 3755 Poster Board III-691 Introduction Diffuse Large B Cell Lymphoma (DLBCL) is the most common lymphoid malignancy accounting for approximately 33% of all newly diagnosed NHLs. Three randomized trials and multiple retrospective analyses have demonstrated both progression-free (PFS) and overall survival (OS) benefit to the addition of the anti-CD20 monoclonal antibody rituximab to anthracycline-containing chemotherapy in older advanced-stage patients, and in young low-risk patients with DLBCL. Approximately half of newly diagnosed patients with DLBCL present in limited stage and the benefit of rituximab containing chemotherapy regimens for these patients remains uncertain. Methods We used an IRB-approved clinicopathologic database, derived from comprehensive tumor registry data at the Massachusetts General Hospital, Dana Farber Cancer Institute and Brigham and Women's Hospital, to identify all patients 18 years or older diagnosed with limited stage DLBCL between 2000 and 2006. We included all patients treated with 3 or more cycles of anthracycline containing chemotherapy with curative intent. We excluded primary DLBCL of the CNS. We determined the impact of the use of rituximab on OS and PFS. PFS and OS were calculated from the date of initial diagnosis. Results A total of 138 patients met eligibility criteria and are included in the analysis. Median age was 51 years (range 18-89 years). 30% of patients were above 60 years of age, and less than 3% had an IPI score of 3 or higher. One hundred and six patients received CHOP + rituximab (RCHOP) and 32 received CHOP alone. Of the 106 patients receiving RCHOP, 48 were irradiated and 58 were not. Of the 32 patients receiving CHOP, 20 received radiation and 12 did not. At a median follow-up of 35 months (range 3-109 months), PFS and OS for the entire cohort are 86.2% and 90.6%, respectively. On univariate analysis of outcome, the addition of rituximab to CHOP did not improve PFS (81.3% vs. 87.7%,p=0.817, Logrank Test) or OS (84.4% vs. 92.5%, p=0.411, Logrank Test). Conclusion The outcome of an unselected series of patients with limited stage DLBCL is excellent. In this retrospective cohort of patients with limited stage DLBCL, the use of rituximab in conjunction with standard chemotherapy did not improve PFS or OS. The results we obtained are very similar to those reported by SWOG (Persky et al. JCO 2008). The overlapping confidence intervals for PFS and OS between SWOG 0014 and 8736 patients and our data suggest that a large multicenter trial will be needed to show a benefit of rituxan in this extremely good prognosis population. Disclosures: Hochberg: Genentech: Speakers Bureau; Biogen-Idec: Speakers Bureau; Enzon: Speakers Bureau; Amgen: Speakers Bureau.

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High Microvascular Density Correlates with Poor Outcome in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab Plus Chemotherapy (R-CT).

Blood ◽

10.1182/blood.v114.22.1948.1948 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1948-1948

Author(s):

Teresa M Cardesa-Salzmann ◽

Luis Colomo ◽

Fina Climent ◽

Eva Gonzalez-Barca ◽

Armando López-Guillermo ◽

...

Keyword(s):

Relative Risk ◽

B Cell ◽

Research Funding ◽

Cell Lymphoma ◽

Cox Model ◽

B Cell Lymphoma ◽

Tissue Sections ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Abstract Abstract 1948 Poster Board I-971 Survival after treatment of diffuse large B-cell lymphoma (DLBCL) is influenced by differences in the tumor microenvironment. Gene expression profiling (GEP) studies have shown that the angiogenesis-related signature (stromal-2 signature) is prognostically unfavorable. However, the clinical and biological significance of angiogenesis quantified in tumor tissue sections of DLBCL from patients treated with rituximab plus chemotherapy (R-CT) is not yet fully explored. CD31, the platelet adhesion molecule PECAM1, is one of the genes included in the “stromal-2 signature” reported in the GEP studies. The objective of this study was to determine whether the microvessel density (MVD) and microvessel number (MVN) in DLBCL patients treated with R-CT were associated with the clinicopathological features of the tumors and related to the outcome of the patients. The MVD and MVN were assessed in a series of 160 patients with DLBCL from the Leukemia Lymphoma Molecular Profiling Project consortium (LLMPP) 86M /74F; median age 64 yrs. The GEP was investigated in 116 of these including 50 germinal center B (GCB), 55 activated B-cell (ABC) and 11 unclassifiable cases. An independent series of 129 patients from the Catalan Lymphoma-Study Group (GELCAB) (67M/62F; median age 64 yrs) was used to validate the results. Front-line treatment was R-CT in all cases of both series. Tissue Microarrays (TMA) were constructed from pretreatment biopsy specimens of de novo DLBCL. High grade B cell lymphoma otherwise unclassifiable, primary mediastinal B cell lymphoma, T-cell-rich B cell lymphoma, and tumors associated with immunodeficiency were excluded. All cases were stained in an automated immunostainer with an antibody against CD31 (DAKO). The MVD and MVN were quantified using digitalized images of the tumor using Olympus Cell B Basic Imaging Software. Microvessel areas were defined as vascular areas delineated by CD31+ staining. The MVD was calculated as the sum of all microvessel areas divided by the total area analyzed. The MVN was the sum of all identified individual vessels, divided by the total area analyzed. TMAs were independently scored by two observers and discrepancies were resolved over a double-headed microscope. To determine whether the angiogenic values scored using the TMA were representative of the tumor sample, whole tissue sections and TMA cores from the same tumor were evaluated in 40 cases and compared by a linear regression analysis. MVD and MVN were grouped in quartiles when necessary and considered high or low when above or below the 50th percentile, respectively. Linear correlation analysis between the CD31 (+) MVD results on TMA cores and on the corresponding whole tissue sections in 40 cases showed a good correlation (R2=0.81). In the LLMPP cohort, DLBCL with an ABC profile showed higher MVD than those with GCB profile (p=0.05). In addition, higher MVD was observed in patients with advanced stage (p<0.01), but there was no significant correlation with other clinical features. 5-yr overall survival (OS) according to CD31(+) MVD was 74% vs. 47% for patients with low and high MVD respectively (p=0.0015). Both the International prognostic index (IPI) (relative risk 3.3; p=0.001) and MVD (relative risk 2.2; p<0.001) showed independent prognostic value for OS in a Cox model. In addition, MVD and GEP type (GCB vs. ABC) were also independent predictors of OS. MVN showed no meaningful relation with initial features or with OS. In the validation cohort from the GELCAB, all the above mentioned results were confirmed, including the influence of MVD on OS (5-yr OS 78% vs. 50% for low and high MVD, respectively; p=0.02) that was also independent of IPI in a Cox model. In conclusion, increased MVD is able to discriminate poor-risk patients in DLBCL treated with R-CT independently of the IPI risk groups. This finding highlights the relevance of angiogenesis in the behavior of these tumors and suggests that it may be an important parameter when assessing the impact of new therapies, particularly anti-angiogenic drugs. Disclosures: Gascoyne: Roche Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Connors:Roche Canada: Research Funding. Rimsza:High Throughput Genomics: .

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Upregulation of CD47 Expression in De Novo Diffuse Large B-Cell Lymphoma Is More Frequent in Activated B-Cell Type

Blood ◽

10.1182/blood-2021-152071 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3507-3507

Author(s):

Winston Y Lee ◽

Anamarija M. Perry ◽

Vero Azcutia ◽

Alex F. Herrera ◽

Pamela Skrabek ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Research Funding ◽

De Novo ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Surface Receptor ◽

Large B Cell Lymphoma ◽

Frequent Mutations ◽

Large B Cell

Abstract CD47 is a marker of self that provides a "don't-eat-me-signal" through activation of signal-regulatory protein alpha (SIRPa), a cell surface receptor expressed on monocytes/macrophages and granulocytes. This interaction negatively regulates effector functions such as, phagocytosis, migration, and superoxide production. Upregulation of CD47 expression in cancer, including diffuse large B-cell lymphoma (DLBCL), has emerged as a mechanism to escape innate immune surveillance. Using conventional immunohistochemical detection, we assessed CD47 expression in DLBCL and interrogated its association with clinicopathologic features. Patients with de novo DLBCL were identified from two large institutions and were uniformly treated with R-CHOP and had sufficient material for study. Immunohistochemical stains (IHC) were performed on FFPE tissue (Hans algorithm, BCL2, MYC, and CD47) and scored semi-quantitatively from no reactivity (0) to strong (2 and 3; Figure 1). Mutational analysis using a 334 gene target sequencing panel, gene expression profiling using Lymph2Cx to determine the cell of origin (COO), and FISH analysis for MYC, BCL2, and BCL6 translocations, were performed. The Lymphgen tool (Wright et al, 2020) was also used to determine the DLBCL group. Fisher's exact test and Kaplan-Meier survival analysis for overall survival (OS) were performed and P <0.05 was considered significant. CD47 expression was assessed by IHC in a cohort of 152 cases of de novo DLBCL, including 107 cases of germinal center B-cell (GCB) type (70%), 37 cases of activated B-cell (ABC) type (24%), and 8 cases of intermediate type (5%). A total of 17 cases (11%) showed strong and diffuse CD47 expression with IHC scores of 2 or above (CD47hi). CD47hi cases were significantly more frequent in ABC DLBCL (24%, 9/37) than GCB DLBCL (6%, 6/107; P=0.003). The remaining 2 CD47hi cases were in the intermediate DLBCL group (25%, 2/8). ABC DLBCL with CD47hi showed more frequent mutations with TET2 (33% vs 7%; P=0.08) and ZFP36L1 (22% vs 0%; P=0.05) compared to cases with low expression of CD47 with IHC scores of less than 2 (CD47low). ABC DLBCL with CD47low showed more frequent mutations of NOTCH2 (18% vs 0%; P=0.31) and MYD88 (29% vs 11%; P=0.4) compared to CD47hi. GCB DLBCL with CD47hi showed frequent mutations of TP53 (67% vs 21%; P=0.026) and CCND1 (33% vs 0%; P=0.003) compared to CD47low. None of the 13 cases with double- or triple-hit for MYC, BCL2 and/or BCL6 showed CD47 expression. The Lymphgen tool showed that cases of DLBCL with CD47hi were mostly in the 'other' group (50%), with other groups represented such as ST2 (21%), EZB (14%), MCD and BN2 (1 case each). There was no difference in overall survival (OS) between CD47hi and CD47low DLBCL (5-year OS, 75% vs 72%; P=0.57), or with the GCB or ABC subtypes. Strong expression with CD47 is more frequent in ABC DLBCL and is seen in a subset of GCB DLBCL with mutations in TP53 and/or CCND1. The level of CD47 expression does not appear to predict OS in patients with DLBCL treated with R-CHOP. This study demonstrates that conventional immunohistochemical methods can readily identify DLBCL with high CD47 expression, and these patients may benefit from the use of anti-CD47 therapy. Figure 1 Figure 1. Disclosures Herrera: Gilead Sciences: Research Funding; Takeda: Consultancy; Tubulis: Consultancy; Karyopharm: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Seagen: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Kite, a Gilead Company: Research Funding.

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Lenalidomide/RCHOP (R2CHOP) Produces High Response Rates and Overall Survival in New, Untreated Diffuse Large B Cell Lymphoma Transformed from Follicular Lymphoma- Results from MC078E

Blood ◽

10.1182/blood-2020-141298 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 47-48

Author(s):

Sanjal H Desai ◽

Betsy Laplant ◽

William R. Macon ◽

Rebecca L. King ◽

Yucai Wang ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Pet Ct ◽

Grade 3 ◽

Large B Cell

Introduction: Transformation of low grade follicular lymphoma (FL) to diffuse large B cell lymphoma (DLBCL) carries a poor prognosis. In retrospective studies, 5-year survival of transformed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) without autologous stem cell transplant is 40-60%, underscoring need to improve frontline treatment of transformed DLBCL beyond R-CHOP. The overall response rate (ORR) to lenalidomide used as a single agent for relapsed transformed non Hodgkin lymphoma was 45% with 21% complete response (CR) rate and a median duration of response of 12 months (Witzig et al, Ann Onc 2011). These data provided the rationale to include patients with transformed DLBCL (with historical and concurrent FL) in MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with new and untreated de novo and transformed DLBCL (NCT00670358). Here we present analysis of the subset of transformed DLBCL patients. Methods: Adult patients with transformed DLBCL and either historical or concurrent FL, stage >=2, measurable disease by Positron Emission Tomography/computed tomography (PET/CT) and adequate organ function were included. Patients with Central Nervous System (CNS) involvement, significant comorbidities, active non-lymphomatous malignancy, life-threatening thromboembolism (TE) and contraindication to aspirin prophylaxis were excluded. Study participants received up to 6 cycles of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), doxorubicin (50 mg/m2), and vincristine (1.4 mg /m2) on day 1, prednisone (100 mg) on day 1-5, pegfilgrastim on day 2, and Lenalidomide 25 mg day 1-10 of 21 day cycle. Tumor lysis prophylaxis was per local practice; patients also received TE prophylaxis with aspirin. Primary outcome was event free survival (EFS) at 12 months, where an event was defined as death, progression or subsequent anti-lymphoma therapy. Secondary outcomes included ORR, CR, progression free survival (PFS), and overall survival (OS). Response was evaluated by PET/CT after cycle 2 and cycle 6 with revised response criteria (Cheson et al, 2007). Adverse events were recorded according to CTCAE version 3.0. The Kaplan-Meier method was used to estimate time to event endpoints. Results: Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. Median age was 64 (range 24-80) years and 18 (54%) were >60 years old. Eighteen (54%) were male, and 32 (97%) had ECOG performance status <2. Twenty-three (70%) had historical FL and 10 (30%) had concurrent FL. Twenty-six (79%) had advanced stage (III-IV). Median number of extra nodal sites were 1 (0-4). Thirteen (39%) had high international prognostic index (IPI) (4-5). Thirty-two (97%) completed at least 2 cycles (30 completed all 6 cycles) and were evaluable for response. ORR was 97% (32/33), 29 (88%) had CR and 3 had PR. EFS at 12 months was 87.9% (95% CI: 71.8, 96.6). Two-year PFS and OS were 84.5% (95% CI: 72.8%-98%) and 96.9% (95% CI: 91-100%) (Figure 1). Twenty nine completed study protocol, 4 discontinued protocol early for disease progression (1), adverse event (AE) (1), refusal (1) and noncompliance (1). Thirty (91%) had hematologic AE of grade 3 or above, 27 (82%) had neutropenia, 16 (48%) had thrombocytopenia, and 7 (21%) had anemia. Sixteen (48%) had grade 3 or above non-hematologic AE. Eight (24%) had febrile neutropenia. There were 3 deaths on this study, 1 due to progressive DLBCL, 1 due to AML and 1 due to malignant melanoma. Conclusion: R2CHOP appears effective in transformed DLBCL with high response rates, event free, progression free and overall survival seen in current study. This study supports the inclusion of anthracycline naive patients with transformed DLBCL in future randomized studies of lenalidomide or other novel immunomodulatory (IMiD) analogues. Disclosures Wang: Novartis: Research Funding; Innocare: Research Funding; Incyte: Research Funding. Ansell:Bristol Myers Squibb: Research Funding; Takeda: Research Funding; AI Therapeutics: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; ADC Therapeutics: Research Funding. Witzig:Spectrum: Consultancy; Immune Design: Research Funding; Karyopharm Therapeutics: Research Funding; Acerta: Research Funding; Incyte: Consultancy; AbbVie: Consultancy; MorphSys: Consultancy; Celgene: Consultancy, Research Funding. Nowakowski:Celgene/BMS: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Ryvu: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; Kymera: Consultancy; Curis: Consultancy; Seattle Genetics: Consultancy; NanoString: Research Funding.

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Shorter Diagnosis-to-Treatment Interval in Diffuse Large B-Cell Lymphoma is Associated With Inferior Overall Survival in a Large, Population-Based Registry

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2020.7654 ◽

2021 ◽

Vol 19 (6) ◽

pp. 719-725

Author(s):

Danielle N. Blunt ◽

Liam Smyth ◽

Chenthila Nagamuthu ◽

Evgenia Gatov ◽

Ruth Croxford ◽

...

Keyword(s):

Overall Survival ◽

Clinical Trials ◽

Treatment Initiation ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Population Based ◽

Time Dependent ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Background: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. Results: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8–13), and median DTI was 37 days (IQR, 22–61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4–2.8 years). Shorter DTI was a significant predictor of mortality (P<.001). Compared with the shortest DTI period of 0–18 days, those who commenced therapy at 19–29 days (hazard ratio [HR], 0.75; 95% CI, 0.68–0.84), 30–41 days (HR, 0.70; 95% CI, 0.63–0.78), 42–57 days (HR, 0.52; 95% CI, 0.46–0.58), and 58–180 days (HR, 0.52; 95% CI, 0.47–0.58) had improved survival. Increasing age (HR, 1.03; 95% CI, 1.03–1.04), male sex (HR, 1.23; 95% CI, 1.14–1.32), and increasing number of comorbidities (HR, 1.12; 95% CI, 1.11–1.13) were associated with inferior survival. Conclusions: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.

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The Impact of Concurrent Expression of MYC and BCL2 on Outcomes of Localized Primary Gastric Diffuse Large B-Cell Lymphoma Undergoing Rituximab-Containing Chemotherapy with or without Radiotherapy

Blood ◽

10.1182/blood.v124.21.1761.1761 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1761-1761

Author(s):

Akihisa Kawajiri ◽

Dai Maruyama ◽

Akiko Miyagi Maeshima ◽

Shin-ichi Makita ◽

Hideaki Kitahara ◽

...

Keyword(s):

Research Funding ◽

Cell Lymphoma ◽

Survival Rates ◽

B Cell Lymphoma ◽

Good Prognosis ◽

Large B Cell Lymphoma ◽

Significant Difference ◽

The Impact ◽

Large B Cell ◽

Overall Survival Rates

Abstract Introduction Although the Japanese multicenter phase II trial in localized primary gastric diffuse large B-cell lymphoma (PG-DLBCL), which evaluated three cycles of CHOP followed by radiotherapy (RT), showed good prognosis (Cancer Sci 2005; 96: 349), reports about outcomes and prognostic factors of localized PG-DLBCL patients in the rituximab era are limited. Recently, it has been reported that the concurrent expression of MYC and BCL2 predicts unfavorable outcome in DLBCL patients treated with R-CHOP (J Clin Oncol 2012; 30: 3460). However, the impact of the concurrent expression of MYC and BCL2 on outcomes of localized PG-DLBCL patients has never been reported. Patients and Methods We retrospectively analyzed 52 consecutive patients diagnosed as having localized (stage I or II according to the Lugano Staging System for Gastrointestinal Lymphomas) PG-DLBCL who were initially treated at our institution between 2003 and 2013. Positivity of MYC in immunohistochemistry was defined as labeling of tumor cells of more than 40% and positivity of BCL2 was defined as more than 70%. The lymphoma cells were assigned a GCB or non-GCB phenotype using the Hans algorithm for determining the cell-of-origin (COO) subtyping. Results Twenty-four (46%) patients were male and 28 (54%) female, with a median age of 62 years (range: 29-85). Thirty (58%) patients presented with stage I disease, 15 (29%) with stage II1, two (4%) with stage II2 and five (9%) patients with stage IIE. Most patients (47 patients; 90%) had low or low-intermediate risk based on the International Prognostic Index. Fifty (96%) patients received R-CHOP with or without RT, and one each received CHOP plus RT, and total gastrectomy followed by rituximab. The median number of CHOP cycles was three (range: 2-8). The majority (43 patients; 83%) of patients were treated with R-CHOP followed by RT. COO subtype could be determined in 48 of the 52 patients (63% GCB and 37% non-GCB). Both MYC and BCL2 expression could be assessed in 47 of the 52 patients, and the concurrent expression of MYC and BCL2 was confirmed in seven (15%) patients. In this analysis, no patients showed positivity for EBER-1 in situ hybridization, which was reported as an adverse prognostic factor of localized PG-DLBCL in the pre-rituximab era. Median follow-up duration was 76 months (range: 4-127 months). Fifty (96%) patients achieved complete responses, and the remaining two without concurrent expression of MYC and BCL2 had primary refractory disease. The estimated 5-year overall and progression-free survival rates of all 52 patients were 90% (95% CI, 75-96%) and 89% (95% CI, 75-95%), respectively (Fig. 1). The estimated 5-year overall survival rates of GCB phenotype and non-GCB phenotype cases were 86% (95% CI, 63-96%) and 93% (95% CI, 59-99%), respectively, with no statistically significant difference (p=0.96). The estimated 5-year overall survival rates of the patients with and without concurrent expression of MYC and BCL2 were 100% and 88% (95% CI, 72-96%), respectively (Fig. 2). There was no significant difference between the two cohorts (p=0.74). Conclusions The results of our analysis showed good prognosis, and revealed that COO subtype and concurrent expression of MYC and BCL2 did not influence the outcome in patients with localized PG-DLBCL treated with rituximab-containing chemotherapy with or without RT. Further investigations, especially a prospective cohort study, are needed to confirm our results. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Maruyama: Eisai Co., Ltd: Honoraria. Kobayashi:Otsuka Pharmaceutical Co., Ltd.: Research Funding; ARIAD Pharmaceuticals, Inc.: Research Funding; Boehringer Ingelheim GmbH: Research Funding. Tobinai:Zenyaku Kogyo: Research Funding; Chugai Pharmaceutical: Research Funding.

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The Impact of IL-6 and IL-10 Gene Polymorphisms in Diffuse Large B-Cell Lymphoma Risk and Overall Survival in an Arab Population: A Case-Control Study

Cancers ◽

10.3390/cancers12020382 ◽

2020 ◽

Vol 12 (2) ◽

pp. 382 ◽

Cited By ~ 2

Author(s):

Sohaib M. Al-Khatib ◽

Nour Abdo ◽

Laith N. AL-Eitan ◽

Abdel-Hameed Al-Mistarehi ◽

Deeb Jamil Zahran ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

University Hospital ◽

Nucleotide Polymorphisms ◽

Arab Population ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

B-cell lymphomas can be classified as Hodgkin and non-Hodgkin lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin Lymphoma (NHL). The incidence of NHL is variable and affected by age, gender, racial, and geographic factors. There is strong evidence that the immune-regulatory cytokines have a major role in hematologic malignancies. In this study, we analyzed the relationship between seven single nucleotide polymorphisms (SNPs) in two selected cytokines (IL-6 rs1800795G > C, rs1800796G > C, rs1800797G > A, IL-10 rs1800871G > A, rs1800872G > T, rs1800890A > T, rs1800896T > C) and the risk and overall survival of DLBCL patients in a Jordanian Arab population. One hundred and twenty-five DLBCL patients diagnosed at King Abdullah University Hospital (KAUH) from the period 2013–2018 and 238 matched healthy controls were included in the study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues. Genotyping of the genetic polymorphisms was conducted using a sequencing protocol. Our study showed no significant differences in the distribution of all studied polymorphisms of DLBCL between patients and controls. The IL-6 rs1800797 was the only SNP to show significant survival results, DLBCL subjects with the codominant model (GG/AG/AA) genotypes and recessive model (AA genotype in comparison with the combined GG/GA genotype) had worse overall survival (p = 0.028 and 0.016, respectively).

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Diffuse Large B-Cell Lymphoma, Not Otherwise Specified: Discordance between Histology and Flow Cytometry in Bone Marrow Examination at Diagnosis

Blood ◽

10.1182/blood-2018-99-117041 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1718-1718

Author(s):

Fernando Martín Moro ◽

Miguel Piris-Villaespesa ◽

Monica Garcia Cosio ◽

Jesus Villarrubia ◽

Juan Marquet Palomanes ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

B Cell ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Survival Outcomes ◽

Not Otherwise Specified ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: Bone marrow (BM) examination is essential in the staging of diffuse large B-cell lymphoma (DLBCL). The assessment of BM involvement includes both histology (gold-standard) and flow cytometry (FC), but few studies have compared BM biopsy (BMB) histologic findings with results of FC analysis of BM aspirate. Discordance between both techniques generates debate about the staging and the prognostic significance in these cases. Methods: We performed a retrospective single-center analysis of patients with DLBCL, not otherwise specified (NOS) diagnosed during a 4-year period (2014-2017). Patients were divided in three groups according to BM findings of BMB and FC at diagnosis. Standard FC was performed by 4-color flow panel until 2016 and by 8-color FC since then. We described main characteristics of each group at diagnosis and analyzed survival outcomes. We applied means of descriptive statistics and Pearson's chi-squared test, and analyzed survival outcomes according to Kaplan-Meier, using Cox regression for comparisons. Results: We analyzed 59 cases, which were divided in three groups: 40 cases (67.8%) presented both negative histology and FC (BMB-/FC-), 10 (16.9%) showed BM involvement using both histology and FC (BMB+/FC+) and 9 cases (15.3%) presented discordant results, all of them with negative histology and positive FC (BMB-/FC+). Clinical and biological characteristics of each group at diagnosis are presented in Table 1. Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% (0.1-2.9) and 3/9 patients presented discordant immunophenotype of lymphoma cells between BM and node biopsy. If we considered BM infiltration as positive in all BMB-/FC+ cases, 4/9 (6.8% of all patients) would be upstaged. First-line treatment was homogeneous in all patients. With a median observation time of 18 months, progression-free survival (PFS) after 2 years was 67%, 22% and 22% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1A), with a multivariate hazard ratio (HR) of 1.9 (95% CI 1.2-2.9, p=0.004) and an univariate HR for FC+ (BMB-/FC+ and BMB+/FC+) vs FC- (BMB-/FC-) of 3.3 (95% CI 1.5-7.3, p=0.003). Two-year overall survival (OS) was 68%, 41% and 33% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1B); multivariate HR was 1.6 (95% CI 1.1-2.6, p=0.042) and univariate HR for FC+ vs FC- was 2.5 (95% CI 1.1-5.9, p=0.035). We found no significant difference between BMB-/FC+ and BMB+/FC+ in survival outcomes. Conclusions: In our series, the group with discordant BM infiltration (BMB-/FC+) presented worsen survival outcomes than BMB-/FC-. Such results should be validated in prospective studies because published series are retrospective and not focused specifically on DLBCL. BM infiltration detected by FC analysis but not by BMB could be considered as extranodal involvement at DLBCL NOS diagnosis. Disclosures García Gutiérrez: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau.

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