R-CHOP Group Research Articles

Impact of transformation on the survival of patients diagnosed with follicular lymphoma that progressed within 24 months.

Background: Progression within 24 months after initiating treatment (POD24) is established as an unfavorable event predicting poor prognosis in patients with follicular lymphoma (FL). However, little is known about the impact of transformation on the outcome of FL patients with POD24 although transformation could be related to early progression and poor prognosis in FL patients.Methods: We investigated the occurrence of transformation and its association with POD24 in FL patients receiving RCVP (rituximab, cyclophosphamide, vincristine and predisone, n = 152), RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and predisone, n = 111), and BR (bendamustine, rituximab, n = 61).Results: With the median follow-up of 48.3 months, disease progression occurred in 94 patients (94/324, 29.0%) including 58 POD24 cases (58/324, 17.9%), and POD24 was more frequent in the RCVP (25/152, 16.4%) and RCHOP (28/111, 25.2%) groups than the BR group (5/61, 8.2%). Transformation was documented in 38 cases, including 22 of which were clinically designated as transformation. Among the 58 cases with POD24, the proportion with transformation differed across groups: RCVP (8/25, 32%); RCHOP (16/28, 57.1%); and BR (5/5, 100%). Transformation accounted for 50% (29/58) of POD24 cases whereas only 9 (9/36, 25%) patients had transformation with progression after 24 months. Patients with transformation within 24 months had the worst survival outcome regardless of POD24.Conclusions: Transformation negatively impacted survival among FL patients more than POD24 itself. With caution, our findings suggest that BR may reduce POD24 more than RCVP or RCHOP. However, BR efficacy may not reduce the occurrence of transformation.

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China.

Background:Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART).Methods:A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS.Results:A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8–29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups.Conclusions:Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.

R-CHOP Versus R-Bendamustine with or without Rituximab Maintenance in Newly Diagnosed Follicular Lymphoma Patients with High SUV at Baseline PET

R-CHOP Versus R-Bendamustine with or without Rituximab Maintenance in Newly Diagnosed Follicular Lymphoma Patients with High SUV at Baseline PET

Evaluation of Dose-Adjusted EPOCH-R Compared with R-CHOP for the Treatment of High-Risk, Aggressive B-Cell Lymphomas: A Single-Center Experience

Introduction High-risk subtypes of DLBCL, including high-grade B-cell lymphomas (HGBCL) with rearrangements of c-MYC (MYC-R), BCL2 and/or BCL6 [or double hit and triple hit lymphomas (DHL/THL)], double expressor lymphoma (DEL), and patients with International Prognostic Index (IPI) scores of 3-5 have a poor prognosis with standard R-CHOP chemotherapy. Treatment intensification with DA-EPOCH-R did not improve outcomes when compared to R-CHOP in the CALGB 50303 trial (Bartlett et al JCO 2019). However, high-risk patients were underrepresented as 36% of patients had IPI scores of 3-5, 0.61% of patients had DHL or THL, 2.6% of patients had MYC-R, and 8.6% of patients had DEL (Bartlett et al JCO 2019). Our purpose was to retrospectively compare DA-EPOCH-R to R-CHOP in the treatment of high-risk DLBCL. Methods Patients ≥ 18 years old who received either DA-EPOCH-R or R-CHOP at Moffitt Cancer Center between 1/2010 - 9/2019 were included. Patients with a diagnosis of DLBCL with IPI score of 3-5, DHL/THL, and/or DEL were included. Patients with primary mediastinal B-cell lymphoma (PMBCL), DLBCL with testicular or central nervous system (CNS) involvement, grade 3b follicular lymphoma, Richter's transformation or IPI score < 2 were excluded. The primary endpoint was complete response (CR) rate and secondary endpoints included progression-free survival (PFS), overall survival (OS), CNS relapse rate, and adverse events (AE). PFS and OS were estimated using Kaplan-Meier curves and differences were established using the log-rank test. Statistically significant difference was considered if p < 0.05. Results The study included 128 patients: DA-EPOCH-R (n=36) and R-CHOP (n=92). General characteristics were similar between groups and included: median age = 66 years (33-85), stage III/IV = 89%, IPI score 3-5 = 87.6%, non-germinal center B-cell (GCB) = 32.8%, DEL = 26.6%, and DHL/THL = 18%. Of note, more patients in the DA-EPOCH-R group were < 60 years old, had MYC-R, and/or were DHL/THL or HGBCL, NOS cases. The CR rates for DA-EPOCH-R and R-CHOP were 72.2% (95% CI: 54.8, 85.8) vs. 68.5% (95% CI: 57.8,78.0), respectively (p=0.831). In a pre-planned subgroup analysis, the CR rates across subgroups, including IPI score 3-5, DEL, and DHL/THL, were not different. There was no difference in PFS between DA-EPOCH-R and R-CHOP (p= 0.33; Figure 1). The 1-year (y) PFS for DA-EPOCH-R and R-CHOP was 69% (95% CI: 56.0, 86.0) and 62% (95% CI: 52.0, 73.0), respectively. The 3 y PFS for DA-EPOCH-R and R-CHOP was 66% (95% CI: 53.0, 84.0) and 46% (95% CI: 35.0, 59.0), respectively. PFS was higher in the DA-EPOCH-R arm for patients with MYC-R (p=0.0224) and DHL/THL (p=0.045). There was no difference in OS between DA-EPOCH-R and R-CHOP (p=0.83). The 1 y OS was 77% (95% CI: 65.0, 92.0) for the DA-EPOCH-R group compared with 81% (95% CI: 73.0, 90.0) for the R-CHOP group. The 3 y OS was 71% and 65% for the DA-EPOCH-R and R-CHOP groups, respectively. The CNS relapse rate was 6.2% in the DA-EPOCH-R group and 2.4% in the R-CHOP group (p=0.301). Of the 4 patients with CNS relapse, 3 were DHL, THL or DEL. There were more grade ≥ 3 AEs in DA-EPOCH-R vs. R-CHOP (97.2% vs. 77.2%; p=0.003). There was significantly more grade ≥ 3 hematologic toxicity in the DA-EPOCH-R group regarding neutropenia (DA-EPOCH-R 91.7% vs. R-CHOP 69.6%; p=0.017) and thrombocytopenia (DA-EPOCH-R 50% vs. R-CHOP 16.3%; p=0.0003). Neuropathy and mucositis were significantly more common in the DA-EPOCH-R arm. Conclusions R-CHOP remains standard of care for high-risk DLBCL subgroups when compared to DA-EPOCH-R (such as non-GCB DLBCL, DEL, and patients with IPI score > 3). Patients with DHL/THL or MYC-R had greater benefit from DA-EPOCH-R compared to R-CHOP. DA-EPOCH-R was associated with increased rates of AEs, including significantly more hematologic toxicity. Disclosures Chavez: AstraZeneca: Speakers Bureau; Celgene: Consultancy; Bayer: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Novartis: Consultancy; Merck: Research Funding; Morphosys: Consultancy, Speakers Bureau; BeiGene: Speakers Bureau; Karyopharm: Consultancy; Genentech: Speakers Bureau; AbbVie: Consultancy; Verastem: Consultancy; Pfizer: Consultancy; Epizyme: Speakers Bureau; Gilead: Consultancy.

RNA Sequencing Analysis in Primary Mediastinal B Cell Lymphoma: Identification of Different Gene Expression Related to Chemoresistance

Background: Primary mediastinal large B cell lymphoma (PMLBCL) is a rare subtype of non-Hodgkin lymphoma mostly diagnosed in young women and is currently recognized as a distinct clinical and biological entity. First line therapy with R-CHOP allows to achieve good remission rates even if chemoresistant cases remain highly challenging from the therapeutic standpoint. As such, we aimed to compare the transcriptome of R-CHOP resistant PMBCL patients to those of chemosensitive patients. Methods:We extracted RNA from embedded paraffin samples and then we performed whole RNA sequencing on 7 patients. Four of them were selected as chemoresistant (Group A), while three of them were classified as responder to R-CHOP (Group B). A First bioinformatics analysis selected a panel of 200 genes significantly differentially expressed in chemoresistant (A) samples versus chemosensitive (B). An unbiased analysis based on different ontology of the genes led to easily identify common signatures that may better profile the two groups of patients. Finally, on a bias analysis, genes were divided into categories in order to identify potential new targets and/or mechanisms of chemoresistance. Results:We identified three genes which may be frankly related to chemoresistance in PMLBCLs due to an overexpression in the group A or a suppression of expression in group B. We selected NFKBIA, the gene which encodes for the IκBα protein, mutated in numerous Hodgkin's lymphoma cells, which cause NFkB to be chronically active in the lymphoma tumor cells. For this reason, we imagine that it could have a major role in the modulation of PMLBCLs sensitivity to chemotherapy. EPHB1 was selected for its very strong expression in the poor prognosis group, since it is one of the most expressed genes and for his association with numerous cancers. The kinase STK 33 appeared overexpressed in group A. A more thorough investigation of this gene might lead to new, significant findings. Conclusions: Our in-silico analyses allowed to identify in PMBCL an unique profile that may modulate sensitivity to chemotherapy. Further analyses may address whether this unique phenotype has clinical implications. We may expect to: i) develop specific therapeutic strategies to target NFkB, EPHB1 and STK33 pathways in PMBCL with a chemoresistant behaviour; ii) correlate the expression profile of resistant PMBCL to other transcriptomes, including those of Hodgkin Lymphomas, Diffuse Large B cell Lymphomas, in order to better profile clinical and biological overlapping features. Disclosures Saglio: Ariad:Research Funding;Incyte:Research Funding;Roche:Research Funding;Bristol-Myers Squibb:Research Funding;Pfizer:Research Funding;Novartis:Research Funding.

DA-EPOCH-R VS R-CHOP in Patients with Primary Mediastinal Large B-Cell Lymphoma: Results of Prospective Randomized Ukrainian Multicenter Study

Background Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct clinical, pathological and molecular subtype of diffuse large B-cell lymphoma (DLBCL), accounts approximately for up to 7% of all its cases and 2-4% of all non-Hodgkin's lymphomas. The standard 1st line treatment of PMBCL does not currently exist. The treatment approaches are still differing all over the world. A few retrospective analysis and lack of prospective data comparing the efficiency of R-CHOP and DA-EPOCH-R regimen, does not allow to establish the best front line treatment options. Aims In current study we aimed to compare the treatment efficacy and toxicity of DA-EPOCH-R and R-CHOP regimens in patients with PMBCL. Patients and methods In the study were included 69 patients with newly diagnosed PMBCL from six Ukrainian centers from Aug 2011 to Dec 2015. Median age was 27 years (range 17-45), 50 females (72,5%) and 19 males (27,5%). Early stages (I-II) had 68,1 % patients, 78,3% of patients had greatest size of the tumor mass in mediastinum more than 10 cm. Patients were randomized in two groups: DA-EPOCH-R (36 patients) or R-CHOP (33 patients). Primary endpoint: 5-year PFS. Secondary endpoints: ORR, CR rate, PR rate, 5-year OS and toxicity rate. Primary and post treatment assessment of disease included PET-CT or CT of the whole body. The treatment efficacy in both groups was evaluated according to Cheson criteria 1999, 2007 and Deauville criteria. Toxicity rates were evaluated according to NCI-CTC V.3.0. All patients received 6 cycles of R-chemo ± mediastinal radiation therapy (30-36 Gy). Results ORR and CR were significantly higher in R-da-EPOCH group: 97.7% vs 85% and 81.8 vs 50%, respectively. 2,3% of patients in R-da-EPOCH group and 15% in R-CHOP didn't respond tothe therapy. There were any relapses after completion of treatment in DA-EPOCH-R group. In the R-CHOP group relapses were observed in 15% of patients (mostly early relapses). All relapses happened within 24 months after treatment. According to the analysis of long-term results, the 5-year PFS in the group of patients treated with DA-EPOCH-R was 90,9 % vs 64,1 % (p = 0.002) in the group of patients treated with R-CHOP. The 5-year OS in the DA-EPOCH-R group was 97.7% vs 73,8 % (p = 0.002), respectively. Neutropenia grade 3-4 was observed in 36,1% of cycles in R-da-EPOCH vs 20,6% in R-CHOP (p < 0.05) and FN in 15,7% vs 14,4% of cycles (p > 0.05). Anemia grade 3-4 was in 6,9% vs 8,7%, respectively(p > 0.05). Thrombocytopenia grade 3-4 was not observed. All cases of non-hematological toxicity were grade 1-2.ConclusionsThese results provide the confirmation by a multi-institutional study that DA-EPOCH-R regimen induses high durable remissions in PMBCL and more effective than traditional R-CHOP. Toxicity was tolerable in both groups, but the rate of neutropenia grade 3-4 was higher, but manageable in the group of R-da-EPOCH than in the group of R-CHOP. Disclosures No relevant conflicts of interest to declare.

Analysis of Factors Influencing Clinical Efficacy of Rituximab on Patients with Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma

To analyze the clinical efficacy and safety of rituximab therapy for patients with Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL), and to explore the factors influencing the clinical efficacy. According to therapeutic regimen, 66 patients with EBV-positive DLBCL were divided into two groups: CHOP group (32 cases) and R-CHOP group (CHOP+ rituximab, 34 cases). The clinical efficacy and the incidence of complication were compared between two groups. The clinical risk factors for the clinical efficacy in patients with EBV-positive DLBCL were confirmed by multivariate Logistic analysis. Compared with CHOP group, the complete remission rate, partial remission rate and the overall effective rate in R-CHOP group all were high (P＜0.05), moreover the disease progression rate in R-CHOP group were low (P＜0.05). The occurrences rate of myelotoxicity, hepatic injury and gastrointestinal reaction were not statistically significantly different between two groups (P＞0.05). Multivariate Logistic analysis showed that the Ann Arbor staging, IPI risk score and Ki-67 positive rate were independent risk factors for the clinical efficacy in patients with EBV-positive DLBCL (OR=2.689, P=0.038; OR=3.232, P=0.025; OR=2.919, P=0.023). The clinical efficacy and safety of the therapy with rituximab on the patients with EBV-positive DLBCL are better. The poor Ann Arbor stage, high IPI risk score and the Ki-67 positive rate are factors affecting the clinical efficacy for the patients with EBV-positive DLBCL.

REPOCH compared with RCHOP for the treatment of diffuse large B-cell lymphoma of activated B-cell type.

e20081 Background: Patients with diffuse large B-cell lymphoma of activated B-cell type (DLBCL-ABC) have a worse prognosis than patients with DLBCL of germinal center origin. Recently, a phase III randomized trial of patients with DLBCL showed no improvement in response rates or progression free survival (PFS) with REPOCH compared to RCHOP. However, the PFS reported in this study was significantly better than expected, indicating that high-risk patients, such as those with DLBCL-ABC, may have been underrepresented. The optimal treatment for patients with DLBCL-ABC remains unknown. Methods: We undertook a retrospective analysis of patients with DLBCL treated in our practice from January 1, 2015 to May 31, 2019. We then examined treatment approaches and outcomes of patients treated for DLBCL-ABC. Results: We treated 136 patients with DLBCL and identified 18 of 136 patients with DLBCL-ABC. There were 9 men and 9 women with a median age of 74 years (range 26-92 years) and a median performance status of Eastern Cooperative Oncology Group 1, (0-2). The median international prognostic index score was 3. Nine of 18 patients were treated with REPOCH, 8 with RCHOP, and one with bendamustine and rituximab (BR). The stage distribution was stage I in 2 patients, stage III in 4 patients, and stage IV in 12 patients. Of 9 patients treated with REPOCH, 9 (100%) achieved a complete remission with no relapses to date. Of 8 patients treated with RCHOP, 6 (75%) achieved a complete remission and 2 had no response and died. The one patient treated with BR failed to respond and died. The median PFS for the 8 patients treated with RCHOP was 19.5 months; whereas, the PFS in the REPOCH group had not been reached at a median follow up of 2 years. Grade 3 and 4 toxicities were more common in the RCHOP group and included cardiomyopathy in 1 patient and two episodes of neutropenic fever (one resulting in septic shock and death). There were no grade 3 or 4 toxicities in the REPOCH group. Conclusions: In this retrospective analysis, our patients with DLBCL-ABC treated with REPOCH had better overall outcomes. A prospective trial in this subset of DLBCL patients is warranted.

Comparison the efficacy and prognosis of different first-line treatment for elderly diffuse large B-cell lymphoma

Objective: To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups. Results: A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, β(2)-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group (P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years (P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group (P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, β(2)-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis (P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma (P<0.05 for both). Conclusions: The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.

1077P - Diffuse large B cell lymphoma in the elderly. A retrospective analysis of standard versus alternative treatments

BackgroundDiffuse Large B cell lymphoma (DLBCL) is usually diagnosed between the 5th-6th decade of life. Its incidence increases with age. Chemotherapy (CT) with R-CHOP is the standard treatment for any age. However, in the clinical practice, alternative treatments with less toxicities are offered to elderly patients. This group of patients is usually not well represented in clinical trials. Our aim is to asses the benefit of standard treatment in this population, as well as discontinuation of treatment and its impact on overall survival (OS). As secondary endpoint, we have analyzed the survival rate in the subgroup of patients older than 75 years of age treated with CT. MethodsA retrospective review was performed in patients ≥65 years who were diagnosed with DLBCL during the years 2013-2015 in the Hospital of Leon. Patients with histological confirmation of the primary diagnosis and who received treatment were included. Results65 patients were analyzed. The average age was 75 years. 64% were male and 30% had stage 4 disease at the time of diagnosis. The CT schemes were: R-CHOP (N=28), R-CEOP (N=11) and R-miniCHOP (N=8). 10 patients had grade 4 AEs. One death ocurred after receiving the first cicle. 70% completed at least 4 cicles of CT. Median OS was 51 months versus (vs) 11 months in favor of R-CHOP group (HR=0,59, p=0,112 IC 95%=0,30-1,13). Results were not statistically significant likely because of the small sample size. 45% of patients had a complete response, 20% had a partial response and 10% had no response to treatment.The main cause of death was disease progression. Median OS was 15 months in both groups, in patients older than 75 treated with CT vs<75 years of age. No statistically significant difference was seen, regardless of the treatment they received. ConclusionsIn clinical practice, age is an important variable to account for when deciding on the management approach for heamatological malignancies such as DLBCL. Although our results show a non-statistically significant benefit in OS of R-CHOP vs other schemes, this could be due to the small sample size. Given the prevalence of elderly population in our country, and the proved benefit of standard chemotherapy in the approach of DLBCL, more studies are needed. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Survival Analysis of 148 Patients with Primary Diffuse Large B Cell Lymphoma

To investigate the clinical outcome of the patients with primary diffuse large B-cell lymphoma（DLBCL）. Clinical data of 148 patients with DLBCL in our hospital and cancer hospital from March 2006 to April 2016 were retrospectively analyzed. Kaplan-Meier analysis was used to estimate progression-free survival（PFS）and overall survival（OS）. 5-year OS and PFS rates were 85% and 69%，respectively. The survival analysis showed that 5-year OS rate of R-CHOP group was significantly higher than that of CHOP alone group（89% vs. 70%，P<0.05）. In univariate analysis，several clinical factors，such as older age（>60 years），poor ECOG score（≥2），advanced stage（Ⅲ-Ⅳ），higher IPI score（≥3），CHOP alone and absence of radiotherapy related with poor survival rate. Furthermore，multivariate analysis showed that age>60 year significantly related with the worse OS. Age >60 year is an important independent prognostic factor to predict worse OS or PFS.

Impact of Initial Treatment Regimen on Outcomes for Diffuse Large B-Cell Lymphoma with Dual MYC and BCL-2 or BCL-6 Expression

Introduction:Genetic rearrangements in both the MYC gene and anti-apoptotic genes such as BCL2 or BCL6 in diffuse large B-cell lymphoma (DLBCL) represent a sub-type of lymphoma, termed “double-hit lymphoma” (DHL) that is associated with poor outcomes and a poor response to standard chemoimmunotherapy regimens such as rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (Petrich et al, Blood, 2014). The incidence of DHL is low at approximately 5-10% of DLBCL presentations. Alternatively, DLBCL cases featuring dual expression of both MYC and BCL-2 and/or BCL-6 (as detected by immunohistochemistry [IHC]) occur more frequently with increasing evidence to suggest this lymphoma-subtype, termed “double-expressor lymphoma” (DEL) may also respond poorly to induction therapy with R-CHOP (Green et al, JCO, 2012). Studies examining outcomes for DEL are often limited by an inability to separate DHL from DEL or lack a direct comparison to R-CHOP and, as a result, optimal induction therapy for DEL remains an unanswered question.MethodsWe performed a retrospective review of outcomes in DEL according to initial treatment regimen (R-CHOP vs intensive therapy) for patients diagnosed from 2013-2016 at the University of Wisconsin. We excluded patients lacking IHC or FISH data for MYC or BCL-2, those receiving a non-anthracycline containing regimen, those with concurrent central nervous system presentation, and those with post-transplant lymphoproliferative disorder. Any patients meeting criteria for DHL (i.e. dual gene rearrangements) were coded as DHL and not coded as DEL regardless of MYC, BCL-2, or BCL-6 expression. Intensive therapy included dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), or rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone (R-hyper-CVAD).ResultsFrom 200 cases of DLBCL, we identified 31 (16%) cases of DEL and 11 (6%) cases of DHL. Twenty-five cases of DEL and 9 cases of DHL were eligible for inclusion in our study. Characteristics were similar between the DHL and DEL cohort, although there were more cases of early stage disease in the DEL cohort (56% vs 11%, P=0.05).For DEL, the median age for the R-CHOP cohort was older compared to the intensive cohort (table 1, 73 vs 63), but both groups had a similar percentage of patients aged >60 years (67 vs 80%, P=0.66). Otherwise, demographics including performance status, stage, and revised international prognostic index score were well balanced between the two treatment groups with the exception of more cases of germinal center B-cell of origin (GCB) within the R-CHOP group (80 v 30%, P=0.03).Complete response rates to induction regimens for DEL were similar between the R-CHOP and intensive group (76 vs 80%, P=0.65). Median progression free survival (PFS) was extended in the intensive cohort although 2 year PFS rates were similar between the two groups (40 vs 50%, P=0.70). Two-year overall survival rates were also similar (80 vs 70%, P=0.65). Kaplan-Meier survival curves (figure 1) illustrate a potential benefit for intensive induction therapy, however this is not statistically significant (hazard ratio 0.69 P=0.65).Compared to patients with DEL, patients with DHL achieved similar complete response rates to induction therapy (76% vs 67%, P=0.67) despite exclusive use of DA-EPOCH-R for all DHL patients. There were more consolidative autologous stem cell transplants (auto-SCT) performed in the DHL group (33% vs 8%, P=0.1). PFS and OS were also similar between DHL and DEL sub-groups (HR 1.09, P=0.91)ConclusionsOur study is amongst the first to compare R-CHOP to more intensive regimens for DEL while also separating DEL from DHL. Our current sample size limits our ability to draw definitive conclusions regarding outcomes by treatment regimen; however, despite lack of statistical significance, there is a trend toward intensive regimens improving PFS and OS in DEL. Our study is also amongst the first to directly compare outcomes for DEL and DHL. Survival for DEL was similar to DHL and may reflect improvements in outcomes for DHL when using intensive regimens or may be related to the increased use of consolidative auto-SCT for DHL. Our sample is part of a planned larger multi-center analysis and an increased sample size may build on the improved survival trend demonstrated for intensive regimens vs R-CHOP observed in our analysis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Epidemiological, Diagnostic, Therapeutic and Evolutionary Profile of Patients with Follicular Lymphoma from 2012 to 2015 in Casablanca (Morocco)

Background: Follicular lymphomas are indolent lymphomas of low incidence in Africa. They are considered incurable, but recent progress has led to a significant increase in survival. The aim of our work is to describe the epidemiological, diagnostic, therapeutic and evolutionary profile of patients followed for follicular lymphoma in Casablanca, Morocco. Patients and methods: During the period of January 1, 2012 to December 31, 2015, were included, all patients diagnosed of follicular lymphoma on a histological and immunohistochemical study of the ganglion or the affected tumor tissue. The treatment was either a therapeutic abstention or chemotherapy with or without Rituximab. Results: 53 (6.4%) of the 841 patients followed-up for non-Hodgkin's lymphoma had follicular lymphoma, only 35 were included in this study. The median age of diagnosed patients was 56.1 years [27; 87] and the sex ratio 2. The primary site was the ganglion in 28 (80%) patients and 71.5% of the patients were at stage III and IV of Ann Arbor at diagnosis. According to the FLIPI score 1 about 1/3 of the patients were classified as low risk, intermediate risk and high risk, respectively. 3 (9.4%) patients were under supervision/observation, 1 patient under CVP, 13 (40.6%) patients on CHOP, 1 patient on R-chloraminophen, 14 (43.6%) on R-CHOP. In the R-CHOP group, 85.7% of the patients were on CR with a median remission of 25.8 months. 3 patients in the R-CHOP group had/received maintenance with rituximab. Discussion and conclusion: Follicular lymphoma is of low frequency and is often revealed by lymphadenopathy. The patients are diagnosed at an advanced stage. The R-CHOP protocol with rituximab maintenance is the most used and best protocol for our patients.

Incidence of interstitial pneumonitis in non-Hodgkin's lymphoma patients receiving immunochemotherapy with pegylated liposomal doxorubicin and rituximab.

Pneumonitis is a rare but severe and potentially fatal adverse effect in chemotherapy of lymphoma. This study is aimed to investigate the incidence of interstitial pneumonitis in non-Hodgkin's lymphoma (NHL) patients receiving immunochemotherapy with pegylated liposomal doxorubicin and rituximab. Lymphoma patients were retrospectively reviewed, and eligible patients were included in this study. According to the chemotherapy regimens, patients were classified in four groups: combination of vincristine, cyclophosphamide, doxorubicin, and prednisone (CHOP group) with rituximab (RCHOP group) and combination of vincristine, cyclophosphamide, pegylated liposomal doxorubicin and prednisone (CDOP group) with rituximab (RCDOP group). Incidence and severity of interstitial pneumonitis were compared among the four groups. Among 757 patients reviewed, 207 patients were included in final analysis. Thirteen patients developed chemotherapy-induced interstitial pneumonitis, and the mean cycle of chemotherapy before the onset of pneumonitis was 4. Incidence rates of pneumonitis were 0, 1.8, 17.4, and 21.1% in CHOP, RCHOP, CDOP, and RCDOP groups, respectively (p<0.001). The mean grades of pneumonitis were 0, 2, 2.5, and 3 in four groups, respectively (p<0.001). After adjustment of confounders, chemotherapy regimens (OR 3.491, 95% CI 1.527-7.981, p=0.003) and neutropenia in previous cycles (OR 2.186, 95% CI 1.281-3.731, p=0.004) were independently associated with the incidence of pneumonitis. Interstitial pneumonitis should be highlighted in NHL patients who received more than 4 cycles of RCDOP chemotherapy regimen, especially in those who had grade 4 neutropenia in the previous cycles of chemotherapy.

R-COMP Vs. R-CHOP As First-Line Treatment for De Novo Diffuse Large B-Cell Lymphoma in Patients Older Than 60 Years: Preliminary Results from a Prospective Randomized Phase 2 Study from the Spanish Group Geltamo

Background and objective. Anthracycline-induced cardiotoxicity is a major issue in the treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL). The use of non pegylated liposomal doxorubicin (Myocet®)has been associated with less cardiotoxicity as compared to conventional doxorubicin in breast cancer, but its benefit in DLBCL has been investigated mostly in retrospective and single-arm prospective studies. The objective of this study was to evaluate the benefit, in terms of cardiac toxicity, of the substitution of conventional doxorubicin as part of R-CHOP therapy by the non pegylated liposomal doxorubicin (Myocet®, R-COMP arm) in older patients (≥60 years) with de novo DLBCL or grade 3b follicular lymphoma (FL).Methods. This is a prospective randomized phase 2 trial (ClinicalTrials.gov Identifier: NCT02012088) of newly diagnosed patients with DLBCL or grade 3b FL ≥60 years old with baseline left ventricular ejection fraction (LVEF) > 55%. Patients were randomized to R-COMP or R-CHOP (in both cases every 21 days for a total of 6 cycles, with a dose of conventional doxorubicin or Myocet® of 50 mg/m2/cycle). The primary end-point was to evaluate the differences in subclinical cardiotoxicity between the two arms of treatment, defined by a decrease in LVEF to ≤ 55% at the end of treatment (measured by echocardiography at 1 and 4 months after the last cycle of chemotherapy). Secondary objectives were efficacy, safety and differences in the variations of cardiac biomarkers (troponin and N-terminal pro B-type natriuretic peptide [NT-proBNP]) through therapy in both arms of treatment.Results.Patient characteristics. A total of 91 patients from 15 Spanish hospitals were included, with a median age of 75 years (range 60-86), 49 (54%) were females. ECOG performance status was 2 in 15 (16%), stage III-IV in 68 (76%) and IPI 3-5 in 56 (63%). A total of 46 patients received R-COMP while 45 were treated with R-CHOP, without significant differences between arms regarding baseline characteristics.Subclinical cardio-toxicity: No differences between arms were observed in the number of patients with LVEF ≤55% determined at the end of treatment or at 4 months (6 [15%] in those treated with R-COMP and 5 [14%] in the R-CHOP arm, p=0.966). However, a higher number of patients in R-CHOP arm increased troponin levels at cycle 6 of treatment (17 out of 24 evaluable patients [71%] in R-COMP group vs. 25 out of 25 evaluable patients [100%] in R-CHOP group, p=0.004) or at the end-of-treatment visit (13 out of 21 evaluable patients [62%] in R-COMP group vs. 20 out of 23 evaluable patients [87%] in R-CHOP group, p=0.05). No differences between both groups were observed in variations of NT-proBNP levels through treatment period and follow-up.Serious adverse events (SAEs): With a median follow-up of 16 months (range 0.7-34), a total of 59 SAEs were reported in 37 patients (39 in 21 patients from R-COMP group and 20 in 16 patients from R-CHOP group), including 18 infections (12 in R-COMP and 6 in R-CHOP), and 14 episodes of febrile neutropenia (9 in R-COMP and 5 in R-CHOP). Four patients showed cardiovascular events: atrial fibrillation (n=1, R-COMP group), supraventricular tachycardia (n=2, R-CHOP group), and myocardial infarction (n=1, R-CHOP group). Efficacy: Overall response (OR) and complete remission (CR) were observed in 72 (96%) and 54 (72%) patients, respectively, without differences between R-COMP group (OR and CR rates of 97% and 72%) and R-CHOP group (OR and CR rates of 94% and 72%) (p=0.775). Conclusions. R-COMP is a feasible immunochemotherapy schedule for patients with de novo DLBCL older than 60 years. However, in our series, the use of non-pegylated doxorubicin instead of conventional doxorubicin was not associated with less decrease in LVEF measured by echocardiography, although the differences in troponin levels merits the need for further evaluation with a higher number of evaluable patients and longer follow-up. DisclosuresSancho:Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celltrion, Inc: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity’s Board of Directors or advisory committees. González-Barca:Roche: Honoraria; Gilead: Honoraria; Servier: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Membership on an entity’s Board of Directors or advisory committees. Martín:Janssen: Honoraria; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Gilead: Membership on an entity’s Board of Directors or advisory committees; Sevier: Honoraria, Membership on an entity’s Board of Directors or advisory committees.

NCCN-IPI Is Superior to aaIPI and IPI in Predicting Survival of DLBCL in the Rituximab Era

ObjectiveInternational prognostic index (IPI) has been widely used for predicting outcome in diffuse large B cell lymphoma. Although the introduction of rituximab to chemotherapy has dramatically improved the outcome of DLBCL, it also changed the prognostic value of IPI. The National Comprehensive Cancer Network IPI (NCCN-IPI) and age-adjusted IPI (aaIPI) were used to evaluate the prognosis for DLBCL in the rituximab era. However which one of them is more powerful in predicting survival remains unknown in Chinese patients.Patients and MethodsA total of 334 patients with de novo diffuse large B-cell lymphoma diagnosed from 2003 to 2012 were included. All patients were treated with CHOP with or without rituximab. They were divided into CHOP and R-CHOP groups. IPI, NCCN-IPI and aaIPI score were recorded. Survival was performed according to the Kaplan-Meier (K-M) curves using the log-rank test. The predictive abilities of PI, NCCN-IPI and aaIPI were investigated by Harrell's C-statistics.ResultCompared with the IPI, the NCCN-IPI and the aaIPI had better discrimination in different scores in all patients treated with or without rituximab. Both the NCCN-IPI and aaIPI had power in discriminating low, low-intermediate and high-intermediate risk groups. In comparison, the NCCN-IPI discriminated low-intermediate and high-intermediate risk groups (5-year overall survival [OS]: 74% vs 50%) better than the aaIPI (5-year OS: 80% vs 62%) in all patients and in the R-CHOP group with the NCCN-IPI 5-year OS: 85% vs 67% while the aaIPI: 87% vs 77%. In the CHOP group, the aaIPI discriminated low-intermediate and high-intermediate risk groups better (5-year OS: 70% vs 25%) than the NCCN-IPI (5-year OS: 60% vs 24%). According to the Harrel C statistic, the NCCN-IPI showed higher discrimination of the different scores (C_index: 0.669 ) than the aaIPI (C_index: 0.663 ) in all the patients (C_index: 0.669 vs. 0.663), especially in the R-CHOP group (C_index: 0.681 vs. 0.636). In the CHOP group, the aaIPI had stronger power (C_index: 0.711 ) than the NCCN-IPI (C_index: 0.683 ) in discriminating different scores.ConclusionThe NCCN-IPI is more powerful than the IPI for predicting survival in the rituximab era. In patients aged 60 or younger and treated with CHOP without rituximab, aaIPI is a preferable tool for evaluating prognosis. DisclosuresNo relevant conflicts of interest to declare.

Management of Elderly Patients with Diffuse Large B-Cell Lymphoma in a Network of Community Oncology Practices in the United States

Introduction: Treatment patterns and clinical outcomes in elderly patients with DLBCL treated outside of clinical trials are poorly characterized. A previous report from Medicare Claims data found that 28% of patients above the age of 66 were treated with rituximab monotherapy or were not treated at all, with corresponding median survival of 18 and 2 months, respectively (Hamlin PA et al., Oncologist 2014; 19:1249-57). We conducted a retrospective chart review of diffuse large B cell lymphoma (DLBCL) patients diagnosed and managed within a community oncology practice network to evaluate treatment patterns and corresponding clinical outcomes.Methods: This was a retrospective observational chart review study of patients aged 60 years and over with newly diagnosed DLBCL. Eligibility criteria required a diagnosis between 1/1/2011 and 12/31/2012, with follow up through 12/31/14, plus no prior therapy for DLBCL. Data were obtained via programmatic query of the US Oncology Network/McKesson Specialty Health electronic health record database. Manual chart review was then performed on a subset of patients (n = 301) to confirm initial findings and gather additional information. Structured data elements were evaluated in univariate and multivariable logistic regression analysis in the subset of patients with stage 2 to 4 disease in order to determine factors associated with treatment with standard R-CHOP. Overall survival (OS) and progression free survival (PFS) were estimated from treatment initiation using the Kaplan Meier (KM) method.Results: 1151 patients who fit the eligibility criteria were identified. Age significantly influenced frontline treatment selection. Table 1 lists the percentage of patients with stage 2 to 4 disease treated with various regimens by age cohorts. "R-CHOP Alternative" was defined as one of the following: less than 6 cycles of R-CHOP, < 80% of full doses of agents in R-CHOP, or use of an alternative regimen like R-CVP, R-CEOP, or bendamustine-R. In multivariable analysis, age (OR=4.07 for age 65-79 and OR=7.98 for age 60-64; p<0.0001), ECOG 0-1 (OR=2.44, p=0.1380), geographic practice region other than south (OR=1.96, p=0.0002), body mass index (OR=2.52 for underweight/normal and OR=1.93 for overweight, p<0.0001 compared to obese), increased albumin (OR=1.49, p=0.0046), and increased bilirubin (OR=0.56, p=0.0081) were identified as clinically relevant predictors of the likelihood of receiving standard R-CHOP chemotherapy.Patients with a documented history of cardiomyopathy, congestive heart failure, EF < 50%, chronic renal insufficiency, or diabetes had a reduced prevalence of receiving standard R-CHOP chemotherapy compared with patients with none of those risk factors (34.3% versus 51.2%, p = 0.0640).Median PFS in the R-CHOP, attenuated R-CHOP, and rituximab monotherapy groups was 51.5 months, 11.0 months, and 8.6 months, respectively. 12- and 24-month OS with standard R-CHOP, R-CHOP alternative, and rituximab monotherapy were 90% and 80%, 78% and 64%, and 74% and 47%, respectively. 2-year OS for patients with IPI 0-2 and IPI ≥3 was 80% and 58%, respectively.Conclusions: As patients with newly diagnosed DLBCL get older, fewer receive standard R-CHOP chemotherapy. Age, performance status, albumin, bilirubin, cardiac and renal function, and the presence of diabetes mellitus affect ability to receive standard R-CHOP. Aggressiveness of treatment correlates with clinical outcomes. [Display omitted] DisclosuresBurke:Incyte: Consultancy; Janssen: Consultancy; Pfizer: Consultancy; TG Therapeutics: Other: Travel Expenses; Millenium: Consultancy. Black-Shinn:McKesson Specialty Health: Employment. Clark:McKesson Specialty Health: Employment. Frytak:McKesson Specialty Health: Employment, Equity Ownership. Espirito:McKesson Specialty Health: Employment. Sharman:Acerta: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Pharmacyclics: Research Funding; TG Therapeutics: Research Funding; Seattle Genetics: Research Funding.

New risk factors and new tendency for central nervous system relapse in patients with diffuse large B-cell lymphoma: a retrospective study.

BackgroundIn patients with diffuse large B-cell lymphoma (DLBCL), central nervous system (CNS) relapse is uncommon but is nearly always fatal. This study aimed to determine the risk factors for CNS relapse in DLBCL patients and to evaluate the efficacy of rituximab and intrathecal chemotherapy prophylaxis for CNS relapse reduction.MethodsA total of 511 patients with newly diagnosed DLBCL treated at the Sun Yat-sen University Cancer Center between January 2003 and December 2012 were included in the study. Among these patients, 376 received R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment, and 135 received CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) as primary treatment. Intrathecal chemotherapy prophylaxis (methotrexate plus cytarabine) was administered to those who were deemed at high risk for CNS relapse. In the entire cohort and in the R-CHOP set in particular, the Kaplan–Meier method coupled with the log-rank test was used for univariate analysis, and the Cox proportional hazards model was used for multivariate analysis. Differences were evaluated using a two-tailed test, and P < 0.05 was considered significant.ResultsAt a median follow-up of 46 months, 25 (4.9%) patients experienced CNS relapse. There was a trend of reduced occurrence of CNS relapse in patients treated with rituximab; the 3-year cumulative CNS relapse rates were 7.1% in CHOP group and 2.7% in R-CHOP group (P = 0.045). Intrathecal chemotherapy prophylaxis did not confer much benefit in terms of preventing CNS relapse. Bone involvement [hazard ratio (HR) = 4.21, 95% confidence interval (CI) 1.38–12.77], renal involvement (HR = 3.85, 95% CI 1.05–14.19), alkaline phosphatase (ALP) >110 U/L (HR = 3.59, 95% CI 1.25–10.34), serum albumin (ALB) <35 g/L (HR = 3.63, 95% CI 1.25–10.51), treatment with rituximab (HR = 0.34, 95% CI 0.12–0.96), and a time to complete remission ≤ 108 days (HR = 0.22, 95% CI 0.06–0.78) were independent predictive factors for CNS relapse in the entire cohort. Bone involvement (HR = 4.44, 95% CI 1.08–18.35), bone marrow involvement (HR = 11.70, 95% CI 2.24–60.99), and renal involvement (HR = 10.83, 95% CI 2.27–51.65) were independent risk factors for CNS relapse in the R-CHOP set.ConclusionsIn the present study, rituximab decreased the CNS relapse rate of DLBCL, whereas intrathecal chemotherapy prophylaxis alone was not sufficient for preventing CNS relapse. Serum levels of ALB and ALP, and the time to complete remission were new independent predictive factors for CNS relapse in the patients with DLBCL. In the patients received R-CHOP regimen, a trend of increased CNS relapse was found to be associated with extranodal lesions.

Aidi Injection-Asisted R-CHOP Chemotherapy for the Treatment of Diffuse Large B-Cell Lymphoma

To investigaate the clinical efficacy of Aidi injection-asisted R-CHOP chemotherapy for the treatment of diffuse large B-cell lymphoma (DLBCL). Fifty-one patients diagnosed as DLBCL in our department from February 2005 to September 2015 were randomly divided into 2 groups. Out of them, 26 patients in one group received R-CHOP chemotherapy asisted by Aidi intravenous infection (Aidi+R-CHOP group), 25 patients were in another group received only R-CHOP chemotherapy (R-CHOP group), 3 weeks for one course, to tally continuous 2 courses. The recent therapeutic efficacy, adverse events, quality of life, sIL-2R level and long-term survival rate were compared between 2 groups. The efficacy of the Aidi+R-CHOP group was significantly higher than that of the R-CHOP group (P<0.05); the incidences of neutropenia and thrombocytopenia were significantly lower than the R-CHOP group (P<0.05); besides, KPS scores were significantly higher than in the R-CHOP group (P<0.05); sIL-2R level in the Aidi+R-CHOP group after treatment was significantly lower than that in the R-CHOP group (P<0.05), however, these data were not statistically different between the two groups before treatment. In addition, 3 and 5-year progression-free survival (PFS) rate in the Aidi+R-CHOP group was significantly higher than that in the R-CHOP group. The use of Aidi injection-asisted R-CHOP chemotherapy for treating patients with diffuse large B-cell lymphoma can increase the patient's tolerance to chemotherapy, improve their quality of life, also reduce the side-effects of chemotherapy, and the trerapeutic effect is more significant than that of R-CHOP regimen alone, thus improving the overall therapeutic efficacy of patients with diffuse large B-cell lymphoma.

Consolidation Radiotherapy Improved Survival in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): A Nationwide Multi-Institutional Registry of 816 Cases in Thailand

IntroductionThe additional benefit of consolidation radiotherapy (RT) following chemotherapy in limited stage DLBCL remains controversial. Previous 5 randomized trials, 4 trials before rituximab era (SWOG 8736, ECOG 1484, GELA 93-1 and 93-4 studies) and 1 trial with R-CHOP combination (Lysa/Goelams 02-03), could not demonstrate a remarkable benefit of RT. The purpose of this study is to explore the benefit of combined modality treatment including the combination of RT and rituximab (R)-based chemotherapy in limited stage DLBCL.MethodsFrom the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were a total of 2,399 patients with DLBCL. We included patients with limited stage DLBCL receiving CHOP/CHOP-liked chemotherapy +/- R and +/- RT. The baseline patient characteristics and clinical outcomes were analyzed according to treatment modalities.ResultsA total of 816 patients with a median age of 56 years (range, 15-91) were included in the study. Male:female was 1:1.1. Majority of patients had primary extranodal diseases (58%), stage II (68%), good performance status (89%), normal LDH (55%) and no B-symptoms (59%). The IPI scores were 0 (30.6%), 1(45%), 2 (20%) and 3 (3.9%), respectively. The modalities of treatment were CHOP alone (48.5%), R-CHOP (26.5%), CHOP+RT (17.9%) and R-CHOP+RT (7.1%). Patients in R-CHOP group were older than in other groups (P =0.001) (Table 1).There was a higher proportion of patients in stage II disease in R-CHOP (74.1%) and R-CHOP+RT (74.1%) groups than in CHOP (66.9%) and CHOP+RT (57.5%) groups (P =0.007), whereas the patients were relatively equally distributed between the IPI scores. Complete response (CR) rate was higher in R-CHOP+RT group (82.8%) than in R-CHOP (75%), CHOP+RT (70%) and CHOP groups (58%) (P<0.001). CR was independently associated with consolidation RT (OR 0.65, 95%CI: 0.45-0.97), rituximab-based therapy (OR 0.66; 95%CI: 0.55-0.79) and IPI score (OR 1.90; 95%CI: 1.41-2.57). With a median follow up of 52 months, 4-year progression free survival (PFS) were 76.4%, 69.4%, 61.4% and 49.9% in R-CHOP+RT, R-CHOP, CHOP+RT and CHOP alone, respectively, (P<0.001) (Figure. 1). The corresponding figures of 4-year OS for each group were 78.6%, 76.3%, 64.3% and 59.6%, respectively (P<0.001) (Figure. 2). Multivariate analysis showed that factors associated with survivals were consolidation RT (HR for PFS 0.63, 95%CI: 0.48-0.82; HR for OS 0.70, 95%CI: 0.53-0.94), rituximab-based therapy (HR for PFS 0.72, 95%CI: 0.64-0.83; HR for OS 0.69, 95%CI: 0.60-0.81) and IPI scores (HR for PFS 1.87, 95%CI: 1.54-2.26; HR for OS 1.96, 95%CI: 1.60-2.41)ConclusionIn limited stage DLBCL, consolidation RT plus R-CHOP yielded a superior outcome compared to R-CHOP, CHOP + RT and CHOP alone. Thus, RT continues to have an important role and should not be omitted in management of limited stage DLBCL in rituximab era.Table 1Comparison of characteristics of patients according to treatment modalitiesClinical characteristicsCHOP alone(n= 396)CHOP + RT(n = 146)R-CHOP alone (n = 216)R-CHOP + RT (n = 58)p-valueMale211 (53%)75(51.4%)125 (57.9%)24 (41.4%)0.14Median age (years)56 (15-90)52 (15-86)60 (17-91)55 (15-81)0.001Age ≥ 60155 (39.1%)51 (34.9%)109 (50.5%)20 (34.5%)0.008Primary extranodal disease226 (57.1%79 (54.1%)136 (63.0%34 (58.6%)0.35Stage Stage I Stage II131 (33.1%) 269 (66.9%)62 (42.5%) 84 (57.5%)56 (25.9%) 160 (74.1)15 (25.9%) 43 (74.1%)0.007B-symptom116 (32.6%)47 (36.2%)58 (31.4%)13 (28.9%)0.76HIV seropositivity15 (4.6%)9 (7.0%)--0.004High serum LDH173 (43.7%)74 (50.7%)95 (44.0%)26 (44.8%)0.51ECOG ≥ 231 (7.8%)22 (15.1%)25 (11.6%)7 (12.1%)0.08IPI Low (IPI =0-1) Low-intermediate (IPI =2) High-intermediate (IPI = 3)312 (78.8%) 75 (18.9%) 9 (2.3%)107(73.3%) 32 (29.1%) 7 (4.8%)157 (72.7%) 48 (22.2%) 11 (5.1%)46 (79.3%) 9 (15.5%) 3 (5.2%)0.35Response Overall response Complete response258 (65.2%) 230 (58.1%)116(79.4%) 103(70.5%)179 (82.9%) 162 (75%)51 (88%) 48 (82.8%)<.0001 [Display omitted] [Display omitted] DisclosuresKhuhapinant:Roche: Honoraria.