Limited-stage Diffuse Large B-cell Lymphoma Research Articles

Benefit of consolidative radiation in patients with extranodal limited-stage diffuse large B-cell lymphoma: a multicenter retrospective study in China.

Approximately 40% of limited-stage (stage I and II) diffuse large B-cell lymphoma (LS-DLBCL) presents with extranodal disease. Extranodal LS-DLBCL may have significant biological differences and associated with worse outcomes than nodal disease. Although rituximab based chemoimmunotherapy is standard of first-line treatment, the role of consolidative radiotherapy (RT) in this particular subgroup is controversial. In this multicenter retrospective study, we evaluated the survival benefit of consolidative RT in patients diagnosed with extranodal LS-DLBCL and received rituximab-based chemoimmunotherapy with or without consolidative RT. A total of 328 patients were included, 129 patients (39.3%) received chemoimmunotherapy and consolidative RT, and 199 patients (60.7%) received chemoimmunotherapy alone. With a median follow-up of 5.1 years (range, 0.3-14.8 years), 5-year progression-free survival (PFS) and overall survival (OS) for all patients were 75.4% and 83.9%, respectively. In multivariate analyses, the addition of consolidative RT was associated with superior OS (P = 0.004) and PFS (P = 0.005). High stage-modified International Prognosis Index (SM-IPI) risk predicted worse OS (P = 0.001) and PFS (P = 0.005). Also, propensity score-matched analyses showed RT improved both OS (hazard ratio [HR] 0.228, 95% confidence index [CI] 0.111-0.467, P < 0.001) and PFS (HR 0.308, 95% CI 0.167-0.566, P < 0.001). Among patients who achieved CR, 49 patients (16.6%) developed disease relapse, of which 30.6% relapsed at local sites. Consolidative RT significantly reduced relapse risk (P = 0.002). Our results demonstrated that consolidative RT significantly improved outcomes in patients with extranodal LS-DLBCL in the rituximab era.

Survival Outcomes of Limited-Stage Diffuse Large B-Cell Lymphoma Treated With Radiation Therapy

BackgroundPatients with favorable risk limited-stage (LS) diffuse large b-cell lymphoma (DLBCL) have shown excellent outcomes without radiotherapy (RT). However, the role of RT for the remainder of LS-DLBCL patients is less well defined. We aimed to investigate whether the addition of RT provided an overall survival (OS) benefit in a real-world cohort of LS-DLBCL patients based on primary site at presentation. Materials and MethodsRetrospective data from 39,745 patients with stage I and II DLBCL treated with front-line combination chemotherapy alone or followed by RT were identified using the National Cancer Database from 2004 to 2015. ResultsThe addition of RT was associated with improved 5-year OS for all LS patients as compared to those treated with chemotherapy alone (85% vs. 80%, P < .001). RT was associated with improved 5-year OS in both the nodal and extranodal disease patients (nodal: 85% vs. 80%, P < .001; extranodal: 83% vs. 79%; P < .001). Extranodal sites with prolonged OS from the addition of RT include skin and soft tissue, head and neck, testicular, and thyroid sites (all P < .02). Breast, bone, lung and gastrointestinal extranodal primary sites had no OS benefit from the inclusion of RT. In multivariate analysis, the addition of RT was an independent factor for improved survival for all LS patients ([HR] 0.84, 95% [CI] 0.81-0.88; P < .001). ConclusionThough there is no consensus on optimal treatment indications for RT in LS-DLBCL, these data suggest certain subgroups may have benefit when RT is added to front-line chemotherapy.

Outcome of limited-stage peripheral T-Cell lymphoma after CHOP(-like) therapy: A population based study of 239 patients from the Nordic lymphoma epidemiology group.

Peripheral T-Cell Lymphomas (PTCLs) are rare, aggressive lymphomas with poor outcomes, but limited-stage disease is infrequent and not well-described. This study reports outcomes and prognostic factors in limited-stage nodal PTCLs in a binational population-based setting. Patients were identified from the Danish and Swedish lymphoma registries. Adults diagnosed with limited-stage nodal PTCL (stage I-II) and treated with CHOP(-like) therapy ±radiotherapy between 2000 and 2014 were included. Medical records were reviewed by local investigators. A total of 239 patients with a median age of 62 years were included; 67% received 6-8cycles of CHOP(-like) therapy and 22% received 3-4cycles, of which 59% also received radiotherapy. Autologous stem cell transplant consolidation was administered to 16% of all patients. Median follow-up was 127 months with 5-years overall survival (OS) of 58% (95% CI: 53-65) and progression-free survival (PFS) of 53% (95% CI: 47-59). In multivariable analysis, age ≥ 60 years and B-symptoms were unfavorable and ALK+ anaplastic large cell T-Cell lymphoma was favorable for survival outcomes. There was no difference in treatment-specific outcome (3-4cycles vs. 6-8cycles of CHOP(-like) ± radiotherapy). Low-risk patients (age < 60 without B-symptoms) had a 5-year OS of 77% (95% CI 67-89%). In the present study of limited-stage nodal PTCL, survival after curative intent chemotherapy +/- radiotherapy was inferior to that of limited-stage diffuse large B-cell lymphoma, but a subgroup of young patients without B-symptoms had very good outcomes. Treatment outcomes after 3-4cycles versus 6-8cycles of CHOP(-like) therapy were comparable.

Localized Nodal Diffuse Large B Cell Lymphoma: Is Radiotherapy Needed?

Introduction: Diffuse large B-cell lymphoma (DLBCL) is clinically, morphologically and genetically a heterogeneous group of malignant proliferation of large B-cell lymphoid cells. At diagnosis, 25% of DLBCL presents as a localized disease.Therapeutic options for localized DLBCL include short-course or extended-course chemotherapy regimens such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with or without radiotherapy. Regarding the number of cycles, the choice differs in the different oncology services and the role of radiotherapy remains controversial. Another frequent issue regarding this pathology is the prognosis of the cell of origin (COO) in the localized form. In the literature, non-germ center (N-GC) subtype is correlated with lower overall survival (OS) when compared to germinal center (GC) . This lower overall survival of the non-GC subtype has not been reported in patients with localized DLBCL. Objectives: The primary objective is to compare progression-free survival (PFS) and overall survival (OS) at 5 years of different therapeutic strategies, including 3-4 cycles of chemotherapy with or without radiotherapy and 6 cycles of chemotherapy with or without radiotherapy. The study's secondary objective is to compare the prognostic significance of COO, GC and non-GC phenotypes in localized DLBCL. Methods: This is a single-center Brazilian, observational, retrospective, descriptive and analytical study, to be carried out at the referenced Brazilian cancer center, A.C. Camargo Cancer Center. The study included patients aged 18 years and over, with a nodal DLBCL diagnosis located in the period between 2007 and 2020. PFS and OS curves were performed in 5 years of the population stratified by treatment and cell of origin. Results: A total of 90 patients with limited-stage nodal DLBCL were included. The group that received 3 or 4 cycles of chemotherapy (n=5) had PFS and OS at 5 years of 75%. The second group received 6 cycles of chemotherapy (n=41) and had PFS and OS at 5 years of 89% and 92%, respectively. The third group (n=17) received 3 or 4 cycles of chemotherapy and radiotherapy, and had 100% PFS and OS at 5 years. The fourth group (n=27) received 6 cycles of chemotherapy and radiotherapy and had PFS and OS at 5 years of 87%. There was no statistical difference between the groups. A total of 76 patients had immunohistochemical data extracted from pathology reports to determine COO by Hans' algorithm. A GC phenotype was observed in 47% of patients (n=36). At 5 years, the PFS and OS for the GC cohort were 94% for both, and for the non-GC cohort 85% and 87% respectively. Conclusion: There was no significant difference in PFS or OS for the therapeutic strategies, including 3-4 cycles of chemotherapy with or without radiotherapy and 6 cycles of chemotherapy with or without radiotherapy. In this analysis, the cell of origin did not show a difference in 5 year PFS or OS for localized nodal DLBCL.

Outcomes with Immunochemotherapy Plus Radiation Versus Immunochemotherapy Alone in Stage I Diffuse Large B-Cell Lymphoma: A Retrospective Study

Introduction Diffuse Large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma with a prognosis highly dependent on the stage of the disease. The mainstay of front-line therapy for limited-stage DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-CHOP-like immunochemotherapy (IC). The impact of combined modality therapy (CMT) with radiation therapy (RT) after IC remains uncertain in the rituximab era. In the pre-rituximab era, studies comparing the efficacy of chemotherapy with or without RT showed heterogenous results. To date, only a few single institutional studies have compared IC versus CMT. The aim of this study is to evaluate the efficacy of standard IC compared to CMT in patients with stage I DLBCL in the rituximab era. Methods Adult patients with stage I DLBCL diagnosed between 2002 to 2015 and seen at Mayo Clinic Rochester were identified. Data were obtained from medical records. All patients were treated with IC (R-CHOP or R-CHOP-like), or IC followed by radiation (CMT). The student's t-test or the Wilcoxon rank-sum test was used to analyze between-group differences, as appropriate. Chi-square or Fisher's exact test was used for categorical variable comparisons. Progression-free survival (PFS) was defined as the time from the date of diagnosis to the date of relapse, death or the date of the last follow-up and was analyzed using the Kaplan-Meier method. Overall survival (OS) was defined as the time from the date of diagnosis to the date of last follow-up or death. Response to treatment was evaluated by treating physicians. Results The study included 123 patients diagnosed with stage I DLBCL with a median follow-up time of 65.9 months for IC arm and 56.2 months for CMT arm. Overall, 78 patients were treated with six cycles of IC, and 45 patients were treated with 2-4 cycles of IC followed by involved-site radiation (2 cycles in 4 patients, 3 cycles in 25 patients, 4 cycles in 16 patients). There were no significant differences in age, sex, or extranodal involvement. In the IC group, 59 patients had cell of origin data available: 44 (56.41%) were GCB subtype and 15 patients (19.23%) were non-GCB subtype. In the CMT group, 21 patients (47%) and 9 patients (20%) had GCB and non-GCB subtypes, respectively. Double-hit lymphoma (defined as rearrangement of MYC together with rearrangement of BCL2 and/or BCL6) was reported in 4 out of 78 patients in the IC arm and 2 out of 45 patients in the CMT arm. There was no significant difference in response rates to frontline treatment between groups. In the IC group, the overall response rate (ORR) was 92% (n=72), and the rate of complete response (CR) was 87% (n=68), partial response (PR) was 5% (N=4), stable disease (SD) was 5% (n=4), and progressive disease (PD) was 5% (n=4). In the CMT group, the ORR was 96% (n=43, all CR); 2 patients achieved SD (4%) and no patients had a PR or PD. With a median follow-up time of 65.9 months for IC arm, 14 patients had died. With a median follow-up of 56.2 months for the CMT arm, 14 patients had died. Median PFS was not reached in the IC group while PFS was more than 10 years in the CMT group (p=0.7851) [Figure 1]. There was no significant OS difference observed in both groups (p=0.2561) [Figure 2]. Conclusion Our study showed no significant difference in OS and PFS between patients with stage I DLBCL treated with IC or CMT. Future research on a larger patient population is needed to evaluate the role of consolidation radiotherapy in early stage DLBCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Extranodal presentation in limited-stage diffuse large Bcell lymphoma as a prognostic marker in three SWOG trials S0014, S0313 and S1001.

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P1180: ARE EXTRANODAL LIMITED-STAGE DIFFUSE LARGE B-CELL LYMPHOMA MORE AGRESSIVE THAN NODAL FORMS?

Background: Limited-stage diffuse large B-cell lymphoma (DLBCL) is associated with favourable outcomes with overall survival of 70-80% at 10 years. Stage-modified IPI (sm-IPI) predicts the risk of relapse and death based on clinical factors that do not include extranodal (EN) involvement, although in some studies it has been associated with worse outcomes. Aims: To analyse the characteristics and outcomes of limited-stage DLBCL in a single center series and evaluate the prognostic impact of EN involvement. Methods: We conducted a retrospective analysis of consecutive patients with newly diagnosed stage I-II DLBCL treated with curative intent at a single centre from 2015 to 2019. Primary central nervous system (CNS) lymphoma, primary testicular lymphoma, primary mediastinal B-cell lymphoma and transformed lymphoma were excluded. Response to therapy was assessed according to Lugano criteria. Overall (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method and comparisons done by the log rank test. Cumulative incidence of relapse was calculated using competing risk models and Gray test for group comparisons. Cox regression was used to identify prognostic factors for PFS. Results: Of 152 patients identified, 53 (35%) had EN disease and 99 (65%) were nodal (N). The most common EN sites were stomach (30%), sinus/nasal cavity (13%), skin and soft tissue (9%) and breast (9%). Seventy-two (47%) had low risk sm-IPI (45 N; 27 EN). Clinical characteristics were similar between both groups, except for stage (stage I in 50.9% of EN vs 32.3% of N cases) and bulky disease (EN 15.1% vs N 37.4%). All patients received R-CHOP (median 6 cycles; range 1-8). Eight patients, all with EN involvement (3 sinus/nasal cavity, 2 breast, 2 bone and 1 orbit), received CNS prophylaxis. Seventeen out of 152 patients received additional radiotherapy (RT), 71% of whom had nodal involvement; 16/17 were irradiated due to bulky disease and/or treatment with abbreviated immunochemotherapy. Globally, 89% patients had a complete response (CR) to treatment: 85% in the N and 96% in the EN group (p=0.212). Nine patients relapsed at a median of 18 (7-52) months after obtaining CR (6 from the N and 3 from the EN group). The 4-year cumulative incidence of relapse was similar: 11.2% (95%CI 9.0-13.9%) in EN and 6.7% (95%CI 5.9-7.5%) in N group (p=0.778). No gastric lymphomas relapsed. The most common sites of relapse were lymph nodes (3), soft tissue (3) and CNS (2). Nineteen (14 N; 5 EN) patients died at a median of 12 (0-47) months after starting treatment, mostly (52.6%) due to lymphoma progression. With a median follow-up of 43 months, 4-year OS and PFS were 87% and 82%, respectively. No significant survival differences were observed in patients with N or EN presentation with a 4-year PFS of 81.8% and 81.3% (p=0.428), respectively. On multivariable analysis adjusting for RT, sm-IPI and bulky disease, EN involvement was not associated with a decreased PFS compared with N involvement (HR 0.77; 95%CI 0.31-1.90; p=0.570). Image:Summary/Conclusion: Our study corroborates the very favourable outcomes of localized DLBCL. We could not find differences in PFS according to N and EN presentations when controlling for other prognostic factors. These results do not support different treatment strategies for EN disease; however, due to limited sample size the role of RT and the prognostic impact of specific locations cannot be fully ascertained.

Four cycles of R-CHOP followed by two applications of rituximab based on negative interim PET/CT: an analysis of a prospective trial

BackgroundR-CHOP with or without radiotherapy is the standard treatment for limited-stage diffuse large B-cell lymphoma (DLBCL). To prevent overtreatment, we assessed whether four cycles of CHOP plus six applications of rituximab was adequate with negative interim PET/CT and the role of consolidation radiotherapy specifically for patients with Waldeyer’s ring DLBCL. One hundred and twenty-nine patients with limited-stage DLBCL were enrolled in this open-label, nonrandomized, single-arm, phase 2 clinical trial (NCT01804127).MethodsAll patients were initially treated with 4 cycles of R-CHOP and underwent interim PET/CT. Patients with negative PET/CT (Deauville scores 1–2) received 2 additional cycles of rituximab monotherapy, unless they had any risk factors (primary mediastinal large B-cell lymphoma, extranodal primary or bulky disease). Otherwise, patients received another 2 cycles of R-CHOP. Patients with partial response on interim PET/CT received another 4 cycles of R-CHOP. No radiotherapy was conducted in Waldeyer’s ring DLBCL patients with negative PET/CT. The primary endpoint was 3-year progression-free survival (PFS). Overall survival (OS) in this study was compared with those from a historical study (NCT 00854568159).ResultsOne hundred fifteen interim PET/CT scans (89.1%) were negative after 4 cycles of R-CHOP. An elevated lactate dehydrogenase level was significantly associated with positive interim PET/CT (P < 0.05). A trend of inferior outcome was observed in patients with positive interim PET/CT in terms of 3-year PFS (78.6% vs. 91.9%, P = 0.24) and 3-year OS (85.7% vs. 95.6%, P = 0.16). There were no PFS or OS differences found between patients treated with 4R-CHOP+2R and those treated with 6R-CHOP from a historical control study. Patients with Waldeyer’s ring DLBCL and negative interim PET/CT achieved a 3-year PFS of 87.2% and a 3-year OS of 89.7%.ConclusionsOur results suggested that for interim PET/CT-negative patients without risk factors, the extra 2 cycles of CHOP might be omitted, and radiotherapy might also be omitted in patients with Waldeyer’s ring DLBCL without compromising the efficacy. These results need to be confirmed in a randomized study.Trial registrationclinicaltrials.gov, NCT 01804127. Date of first registration: 05/03/2013.

Clinical and Survival Outcomes in Patients with Supra-Diaphragmatic Vs İnfra-Diaphragmatic Diffuse Large B Cell Lymphoma

Limited-stage diffuse large B-cell lymphoma (DLBCL) accounts for approximately 30% of all DLBCL cases. This study aimed to investigate the impact of the lymphoma involvement side relative to the diaphragm on clinical and survival outcomes in patients with limited-stage DLBCL treated with first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Data from 93 patients with limited-stage DLBCL between 2010 and 2019 receiving R-CHOP were retrospectively analyzed. Patients were divided into two subgroups according to the side of the diaphragm: 29 patients with infradiaphragmatic (InD) and 64 patients with supradiaphragmatic (SpD). There were no significant differences in survival outcomes [5-year PFS rate of SpD and InD groups, 76.7% and 85.7%, respectively (P =0.553); 5-year OS rates of SpD and InD groups, 82.1% and 89.1%, respectively (P = 0,524)] and clinical characteristics, except that extra nodal involvement was dominant in the InD group and the SpD group had a higher IPI. In conclusion, in early-stage DLBCL, extra nodal involvement is expected more if the primary involvement area is below the diaphragm, however whether the primary involvement area is below or above the diaphragm has no effect on survival outcomes. The results of this study need to be confirmed by further studies with a larger case group.

First-Line Treatment and Survival of Stage I(E) Peripheral T-Cell Lymphoma in the Netherlands; A Nationwide Population-Based Cohort Study

Introduction: Peripheral T-cell lymphomas (PTCL) comprise a heterogenous group of mature T-cell neoplasms with generally an unfavorable prognosis. Presentation of PTCL with stage I(E) disease, according to the Ann Arbor classification, is uncommon. Clinical trials in diffuse large B-cell lymphoma (DLBCL) support the use of an abbreviated treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone combined with radiotherapy (combined modality therapy (CMT)) in case of stage I(E) disease. CMT in stage I(E) PTCL has been adapted in daily practice, but clinical trials are lacking. A recent population-based study conducted in Scandinavia indicated that the outcome in patients with limited stage PTCL is as poor as in patients with extensive disease. However, the outcomes of different treatment modalities were not analyzed.Aim: The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL in comparison to advanced stage PTCL.Methods: All newly diagnosed patients ≥ 18 years with stage I(E) PTCL who were diagnosed in 1989-2018 were identified in the Netherlands Cancer Registry (NCR). Survival follow-up was available through February 1, 2021. The PTCL subgroups analyzed included anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma (EATL) and peripheral T-cell lymphoma NOS (PTCL NOS). Patients were categorized according to treatment regimen, i.e. chemotherapy, chemotherapy followed by autologous stem cell transplantation (ASCT), radiotherapy, CMT, and no/other therapy. Calendar period analyses (1989-1999 and 2000-2018) were conducted to assess trends in primary therapy and overall survival (OS) over time. The calendar periods were defined according to the implementation of CMT in patients with limited stage DLBCL from approximately 2000 onward in the Netherlands. The primary endpoint was OS, defined as all-cause-death post-diagnosis.Results: From 1989 to 2018, 854 patients with a median age of 62 years were diagnosed with stage I(E) PTCL, accounting for 19% of all PTCL diagnoses. In stage I(E), the predominant PTCL subtype was PTCL NOS (40%, n=343). Furthermore, 26% (n=222) of patients were diagnosed with ALCL, 3% (n=28) with AITL, 11% (n=93) with EATL and 20% (n=168) with other histological subtypes. In contrast, for patients with advanced stage disease, 42% was diagnosed with PTCL NOS, 23% with ALCL, 24% with AITL, 6% with EATL and 5% with other histological subtypes .To evaluate treatment and survival outcome in patients with stage I(E) PTCL, patients with ALCL, AITL, PTCL NOS and EATL were included for further analyses (n=686). Patients with ALCL, AITL and PTCL NOS were most commonly treated with CMT (n=164; 28%) or chemotherapy only (n=154; 26%). Only 10 patients (1%) received chemotherapy followed by ASCT. The remaining patients were treated with either radiotherapy only (n=116; 20%) or received other/no therapy (n=149; 25%). More patients were treated with CMT in 2000-2018 as compared to 1989-1999 (36% versus 17%, p<0.01). Patients with EATL were most commonly treated with either chemotherapy only or other/no treatment (both n=45; 48%), while 3 patients (4%) received chemotherapy in combination with ASCT (n=2) or CMT (n=1). In EATL, no differences in treatment strategy were observed over time.Overall, 5-year OS for all stage I(E) PTCL was 52%. There was no significant difference in outcome between the two time periods (53% vs. 52%, p=0.92). EATL had a worse prognosis when compared to ALCL, AITL and PTCL NOS (5-year OS 15% vs. 58%, respectively; p<0.01). Five-year OS was significantly higher for patients with ALCL, AITL and PTCL NOS treated with CMT (71%) as compared to patients treated with either chemotherapy alone or with radiotherapy alone (52%, and 53%, respectively; p<0.01). Independent predictors for poor prognosis were higher age, male gender and EATL subtype whereas CMT was associated with a lower risk of mortality when evaluated for in multivariable analysis.Conclusions: For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 58%. This compares favorably to the reported outcomes in advanced stage disease. EATL, even when presenting with limited stage disease, is associated with a very poor prognosis. CMT is associated with superior OS when compared to either chemotherapy or radiotherapy alone. DisclosuresVan Der Poel: Roche, Janssen, Abbvie: Honoraria. Kersten: Kite/Gilead: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy; Miltenyi Biotech: Consultancy; Novartis: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy. Mutsaers: BMS: Consultancy; AstraZeneca: Research Funding. Woei-a-Jin: University Hospitals Leuven, Belgium: Current Employment; Recordati: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Kyowa Kirin: Research Funding.

Extranodal Presentation in Limited Stage DLBCL As a Prognostic Marker in Three Sequential SWOG Trials S0014, S0313 and S1001 (NCT00005089, NCT00070018, NCT01359592)

Extranodal Presentation in Limited Stage DLBCL As a Prognostic Marker in Three Sequential SWOG Trials S0014, S0313 and S1001 (NCT00005089, NCT00070018, NCT01359592)

Biological and Classical Prognostic Factors with Impact on Overall Survival in Patients with Early Stage (I/II) Diffuse Large B-Cell Lymphoma: A Study from the Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype. Early stage (I/II) disease is seen in up to 30% of all DLBCL cases, and although outcomes in this subgroup have been reported as optimal, relapses can still occur. Prognostic models such as the International Prognostic Index (Miller, NEJM, 1998) continues to be utilized for risk stratification in DLBCL. However, despite its limitations and lack of validation in specific demographic groups such as Latin American patients, no prognostic models exist for the evaluation of limited stage DLBCL. Therefore, we aim to investigate different clinico-epidemiological and laboratory variables and its impact on survival in early stage DLBCL.Methods: We conducted a retrospective study of newly diagnosed patients with early stage DLBCL. Using the Grupo de Estudio Latinoamericano de Linfroproliferativos (GELL) database, we selected patients that had early stage disease, defined as non-bulky stage I or II. The variables analyzed included demographic and clinical variables (e.g., age, ECOG performance status), the International Prognostic Index (IPI), and laboratory variables such as serum albumin, serum lactate dehydrogenase (LDH), serum beta-2-microglobulin, the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (LNR), and the platelet-lymphocyte ratio (PLR). To determine the variables associated with mortality, univariate and multivariate Cox regression (step-wise type) analysis was performed. Kaplan-Meier and log-rank test were used for survival analysis. Outcomes with a p-value <0.05 were considered statistically significant.Results: We identified 1,375 patients with DLBCL; 503 were identified as early stage DLBCL of whom 498 had sufficient data for analysis. Almost all cases (n=483, 96%) had nodal disease as the primary site, and 15 (4%) extranodal, all within the gastrointestinal tract. There was a slight female predominance (51.8%). The median age at diagnosis was 64 (IQR: 50 -73) with 57.4% older than >65 years. ECOG performance status of <2 was seen in 77.2% of cases; elevated serum LDH in 32.4%; and elevated serum beta-2-microglobulin in 5.6% (n=11/192). Based on previous data, we evaluated and calculated variables that have been suggested as independent negative prognostic factors for overall survival; the proportion of patients with serum albumin <3.5 mg/dL; LMR <2, NLR >4, and PLR >376 was 34.4%, 10.3%, 9.2%, and 4.7% respectively. With a median follow-up of 45 months, the median 5-year overall survival (OS) rate was 72%. The therapy approaches used, response rates and outcomes with these approaches will be presented at the meeting. Results of the univariate and multivariate analysis are summarized in Table 1. We found that age over 65, ECOG performance status, serum albumin level, beta-2-microglobulin level, LDH ratio, LMR, NLR, PLR, and BCL-2 positivity by immunohistochemistry (IHC) were prognostic factors for OS in the univariate analysis. However, in the multivariate analysis, only NLR, serum albumin level and ECOG performance status were independent factor for worse prognosis. Survival rates were significantly shorter in patients with serum albumin <3.5 g/dL (5-year OS of 49% versus 79%, respectively; p<0.0001); NLR >4 (5-year OS of 46% versus 73%, respectively: p=0.0013); and ECOG performance status ≥2 (5-year OS of 51% versus 74%, respectively; p<0.0001) (Figures 1 to 3).Conclusion: In this large cohort of Latin American patients with early stage DLBCL most patients were older than 65, had nodal disease as the primary site, good performance status, with only a third of patients exhibiting elevated LDH. Moreover, we found serum albumin <3.5 g/dL, NLR >4 and ECOG ≥2 as negative prognostic factors for poor survival in early stage DLBCL. We are currently validating our findings in a prospective cohort of Latin American DLBCL patients and to improve clinical decision-making in those deemed at high-risk for early mortality. [Display omitted] DisclosuresOtero: Astra Zeneca: Current Employment. Oliver: Roche: Other: conference support and fees ; Abbvie: Other: conference support and fees . Castillo: Abbvie: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy; Roche: Consultancy; TG Therapeutics: Research Funding.

Characteristics and Outcomes of Patients with Double-Protein Expression in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): Analysis of SWOG Study S1001 (NCT01359592)

Characteristics and Outcomes of Patients with Double-Protein Expression in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): Analysis of SWOG Study S1001 (NCT01359592)

Impact of Immunohistochemistry-Defined Cell of Origin and MYC Rearrangements on Outcomes in Patients with PET-Defined Stage I/II Diffuse Large B-Cell Lymphoma Treated with R-CHOP ± Radiotherapy: An International Multi-Center Retrospective Study

Impact of Immunohistochemistry-Defined Cell of Origin and MYC Rearrangements on Outcomes in Patients with PET-Defined Stage I/II Diffuse Large B-Cell Lymphoma Treated with R-CHOP ± Radiotherapy: An International Multi-Center Retrospective Study

Limited-stage diffuse large B-cell lymphoma: current management and challenges.

Twenty-five to thirty per cent of diffuse large B-cell lymphoma (DLBCL) presents as limited stage (I-II). Prognosis is generally excellent with four to six cycles of R-CHOP alone (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisolone) or combined-modality therapy with three or four cycles and involved-site radiotherapy (RT). There is growing interest in optimising algorithms to retain disease control whilst minimising long-term toxicity, with several recent studies focusing on the safety of abbreviating chemotherapy and omitting RT in low-risk patients and the utility of PET-based response-adapted approaches. As these studies are limited to younger patients without risk factors, application of similar approaches in elderly or higher-risk patients is hampered by a lack of evidence. Whilst there has been a move away from using RT in low-risk patients, it remains a useful adjunct in specific situations. Current evidence cannot exclude a clinically meaningful benefit from RT even in low-risk patients and, given the low expected toxicity from modern RT techniques, a risk-benefit assessment should be individualised and considered in a multidisciplinary fashion. The optimal approach for extranodal limited-stage DLBCL (~40% of cases) varies according to site of origin. Herein we discuss the latest clinical trial evidence and how this can be applied in routine practice.

Characteristics and Management of TP53-Mutated Diffuse Large B-Cell Lymphoma Patients.

Background/AimTP53 mutation is recognized as a negative prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL). Here, we present the characteristics of TP53mut DLBCL patients following investigation of the effect of a treatment approach on survival of TP53mut DLBCL patients.MethodsA total of 44 DLBCL patients with TP53mut and treated with an R-CHOP regimen were included for analysis. Patients who failed to achieve a complete response (CR) to initial treatment or relapsed in the first 6 months after initial CR were deemed to have primary refractory disease.ResultsAmong 44 patients harboring TP53 mutations who underwent upfront R-CHOP or R-CHOP–like treatment, 21 (47.7%) had limited-stage and 23 (52.3%) presented advanced-stage disease. Apart from the seven patients receiving upfront surgical resection, 37 had measurable disease under the R-CHOP regimen, with 59.1% (n=26) developing primary refractory disease. Seven limited-stage patients after early complete resection and one with residue resection remained event-free at median follow-up of 37 months. Multivariate analysis revealed that elevated baseline lactate dehydrogenase (LDH), extranodal involvement (two or more), Ann Arbor stage, and locoregional treatment (surgery or radiation therapy) were independent indicators for progression-free survival (PFS). After adjustment for baseline LDH and extranodal involvement, adding locoregional treatment including surgery and radiation to the R-CHOP regimen significantly improved PFS (p=0.008) and overall survival (p=0.017) in limited-stage TP53mut DLBCL patients compared to R-CHOP–only treatment.ConclusionThis study presents the characteristics of TP53-mutated DLBCL and implies a potential benefit of locoregional treatment in limited-stage DLBCL patients with TP53 mutations.

Long-term follow-up of abbreviated R-CHOP chemoimmunotherapy for completely resected limited-stage diffuse large B cell lymphoma (CISL 12-09).

The standard of treatment for completely resected limited-stage diffuse large B cell lymphoma (DLBCL) in patients without residual lesions has not yet been established. Previously, we designed a phase II trial to evaluate the safety and efficacy of three cycles of abbreviated R-CHOP in patients with completely resected limited-stage DLBCL and reported favorable survival outcomes. We present the long-term follow-up results to taking into account the importance of delayed relapse in patients with limited-stage DLBCL. With a median follow-up duration of 62.7months (range, 60.2-75.5months), the 5-year OS and DFS rates were both 95.0% (95% confidence interval, 85.59-104.11%). Only one patient experienced disease progression which was confirmed at 12.3months, and one patient with primary intestinal DLBCL developed non-small cell lung cancer 6years after treatment. The long-term results of our data support the use of three cycles of abbreviated R-CHOP for patients with completely resected limited-stage DLBCL. The study was reviewed and approved by the review boards of the participating institutes and registered at ClinicalTrials.gov , number NCT01279902, in August 3, 2010.

Comparison of Clinical Features Between Primary and Secondary Breast Diffuse Large B Cell Lymphoma: A Yokohama Cooperative Study Group for Hematology Multicenter Retrospective Study.

We performed a retrospective analysis of DLBCL with breast involvement to compare the prognosis of primary breast lymphoma (PBL) to secondary breast lymphoma (SBL; especially in limited stage cases). We retrospectively reviewed records of 25 diffuse large B-cell lymphoma (DLBCL) patients with breast involvement who received chemotherapy between January 2000 and August 2012. We compared clinical features and prognosis among patients with PBL (n = 11), limited stage SBL (LSBL; n = 6), and advanced stage SBL (ASBL, n = 8). The PBL group had significantly lesser patients with breast tumours (BTs) > 5cm than the SBL group (P = 0.02). After a median follow-up of 71.3months, we observed significantly better 5-year overall survival (OS) in the PBL group (90.0%) than in the LSBL (33.3%, P = 0.01) group, but not for progression-free survival (PFS). Patients with BT > 5cm had worse OS (P = 0.01) and PFS (P = 0.04) than those with BT ≤ 5cm. PBL had a better prognosis than SBL among limited stage DLBCL.

Long-Term Follow-up of a PET-Guided Approach to Treatment of Limited-Stage Diffuse Large B-Cell Lymphoma (DLBCL) in British Columbia (BC)

Background: Treatment practices for patients with limited-stage DLBCL are varied and include combined-modality treatment (3 cycles immunochemotherapy + radiation therapy) or immunochemotherapy alone. Since 2005, patients (pts) in BC with limited-stage DLBCL (stage I/II, no B-symptoms, mass &amp;lt; 10cm) have been treated according to a PET-guided algorithm. Following 3 cycles of R-CHOP, pts undergo FDG-PET/CT scan; PET-negative pts receive one additional cycle of R-CHOP, while PET-positive pts receive involved-site radiation therapy (RT). We present long-term follow-up of this population-based experience. Methods: Using the BC Cancer Lymphoid Cancer Database we identified all pts who were diagnosed with limited-stage DLBCL from Mar 2005 to February 2019 and underwent a PET/CT after 3 cycles of curative-intent R-CHOP, in keeping with the PET-guided policy. Pts with primary CNS, primary testicular, PMBCL, PTLD, and transformed/discordant/composite lymphoma were excluded. Pts with evidence of progressive disease prior to or on mid-treatment PET/CT were also excluded. All PET/CT scans were performed and reviewed centrally. Prior to 2014, interpretation was based on the International Harmonization Project (IHP) criteria, and subsequently according to Deauville criteria. Importantly, uptake greater than the mediastinal blood pool was consistently used to determine PET-positivity (ie. PET-positive by IHP, or D3-5 by Deauville). Results: Clinical characteristics of the 319 pts identified are as follows: median age, 68 y (range 19-92); 48%, male; 59%, stage I; 41%, stage II; 8%, PS&amp;gt;1; 13%, elevated LDH; 52%, at least 1 extranodal site; 37%, mass size ≥ 5cm. Stage-modified IPI risk score: 19%, 0; 45%, 1; 27%, 2; 9%, 3-4. Median follow-up is 6.25 yrs (range 0.42-14.25). After 3 cycles of R-CHOP: 254 pts (80%) were PET-negative; 59 pts (18%) were PET-positive; and 6 pts (2%) were considered PET-indeterminate (by IHP). Elevated serum LDH (p&amp;lt;0.001), mass size ≥ 5cm (p=0.008) and stage-adjusted IPI (p=0.025) were predictive of PET-positive status. Of the 254 PET-negative pts, 234 (92%) completed treatment with one additional cycle of R-CHOP, 7 (3%) stopped treatment after 3 cycles R-CHOP and 13 (5%) received RT due to poor chemotherapy tolerance or physician choice. 21/254 PET-negative pts have relapsed and 2/254 died of treatment-related toxicity. 8/21 (38%) PET-negative relapses were late, occurring more than 4 years post initial diagnosis. 55/59 (93%) PET-positive pts received RT, 2 pts refused RT and received only 3 cycles R-CHOP, and 2 pts received 1 additional cycle of R-CHOP alone due to physician preference. 13/59 PET-positive pts have relapsed, only 2/13 (15%) relapses were late &amp;gt;4 years from diagnosis. Of the 6 PET-indeterminate patients, 2 received RT and 3/6 have relapsed. Overall 5-year time-to-progression (TTP) censoring deaths from unrelated causes is 89% (92% for PET-negative and 80% for PET-positive pts). Overall 5-year PFS is 84% (88% for PET-negative and 74% for PET-positive pts) and 5-year OS is 87% (90% for PET-negative and 77% for PET-positive pts). On univariate analysis, age&amp;gt;60, PS&amp;gt;1, stage-modified IPI, and PET status were significant predictors of TTP. On multivariate analysis controlling for age&amp;gt;60, stage, PS, LDH, presence of extranodal involvement, mass size ≥ 5cm, and PET status, only age (p=0.002) and PET status (p=0.004) remained independent predictors of TTP. Conclusion: Using a PET-guided approach to treatment, the majority of patients with limited-stage DLBCL have negative PET scans after 3 cycles of R-CHOP. Patients with negative PET scans have an excellent outcome when treated with 4 cycles of R-CHOP alone, without exposure to radiation. Patients with a positive PET scan who complete treatment with radiation therapy have a slightly less favorable outcome, and may be appropriate for alternative approaches. A detailed analysis of patterns of relapse, as well as efforts to identify clinical factors, PET parameters and biomarkers associated with poor outcome and delayed relapse are ongoing. Figure Disclosures Sehn: Acerta: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria. Scott:NanoString: Patents &amp; Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Abbvie, Sanofi: Consultancy, Honoraria; Astellas Inc.: Research Funding. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria.

PET-Directed Therapy for Patients with Limited-Stage Diffuse Large B-Cell Lymphoma - Results of Intergroup Nctn Study S1001

PET-Directed Therapy for Patients with Limited-Stage Diffuse Large B-Cell Lymphoma - Results of Intergroup Nctn Study S1001