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Although outcomes of transformed diffuse large B-cell lymphoma (DLBCL) from follicular lymphoma (FL) were improved using rituximab-combined immunochemotherapy, the efficacy of subsequent rituximab maintenance (RM) remains unclear. We retrospectively analyzed the prognoses of 519 patients with de novo DLBCL and 62 patients with concurrent DLBCL and FL (concurrent-DLBCL/FL). Progression-free survival (PFS) was shorter in patients with concurrent-DLBCL/FL than in de novo DLBCL (p=.030). Twenty-four patients with concurrent-DLBCL/FL received RM after induction therapy, and they achieved better OS and PFS (p=.010 and p

Peripheral T-cell lymphoma (PTCL) is a group of aggressive lymphomas commonly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Progression-free survival at 24 months (PFS24) constitutes a survival predictor for some lymphomas but has not been examined in Asian populations. We retrospectively investigated whether PFS24 was predictive of survival outcomes after CHOP treatment in 73 Japanese patients with PTCL. Patients without PFS24 had shorter median subsequent overall survival (OS) (20.2 vs. 121.0 months

Somatic gene mutations related to acceleration disease and clonal evolution in multiple myeloma strongly influence severe clinical outcomes. In this study, we traced the transition of somatic mutations during the clinical course of myeloma patients over a long-term follow-up period (8.5 year average). Seven myeloma cases treated with immuno-chemotherapy at our institution were analyzed with clinical courses and the results of FISH and G-band analyses. Furthermore, the target sequences in regard to 121 genes, related to driver mutations or acceleration of disease in myeloma, were performed using bone marrow myeloma samples by next-generation sequencing, Ion Proton™ System. We detected a relationship between an increase in the dominant mutated gene (e.g., TP53, DIS3, FAM46C, KDM6B, and EGR1) and poor prognosis. In particular, clonal escalation of the TP53 mutation could not be overcome by any treatment. The selection of a combination treatment conducted in conjunction with the monitoring of gene mutations is appropriate for long-term survival. Our data demonstrate that long-term follow-up of somatic gene mutations during the clinical course of myeloma is helpful in the development of an effective treatment strategy.

Background High-risk cytogenetic abnormality (CA) influences the prognosis of multiple myeloma (MM) even in the era of novel agents. However, prognostic heterogeneity could exist in MM patients with high-risk CA and additional cytogenetic aberrations are possibly correlated with worse outcomes. We conducted a retrospective study in patients with MM with high-risk CA to evaluate whether the outcomes are different in each high-risk group and whether the existence of additional chromosomal abnormalities would lead to poor outcomes. Method Patients with newly diagnosed MM (NDMM) in our institute between February 2006 and December 2020 were enrolled in this retrospective cohort. We analyzed only patients who were treated with novel agents including proteasome inhibitor and/or immunomodulatory drugs. All of cytogenetic abnormalities were analyzed from bone marrow samples. In this cohort, we defined high-risk CA as del(17p), t(4;14), t(14;16), and/or 1q21 gain, all of which were identified using FISH analysis. We surveyed additional chromosomal aberrations using G-banding testing. Complex chromosomal abnormality was defined as three or more chromosomal aberrations accompanying with at least one structural aberration. The survival was calculated by the Kaplan Meier method, and statistical analysis was performed by the Log-rank test. Factors affecting OS and PFS were evaluated using Cox proportional hazard model. Results We analyzed 36 MM patients who had high-risk CA at initial diagnosis. Twelve patients had del(17p), 16 had t(4;14), four had 1q21 gain, and four had more than one high-risk CA; two patients with t(4;14) and 1q21 gain, one with del(17p) and 1q21 gain and one with del(17p), t(4;14), and 1q21 gain. G-banding testing showed that patterns of complex chromosomal abnormality were found in nine patients. No significant differences in progression-free survival (PFS) and overall survival (OS) were seen between each high-risk CA group. The tendency of shorter PFS and OS was observed in patients with concurrent complex chromosomal karyotype than patients with no additional chromosomal aberrations. Furthermore, we found that the existence of complex cytogenetic abnormality by G-banding was correlated with poor PFS by multivariate analysis (hazard ratio 4.01, 95% confidence interval 1.35–11.9, p = 0.012). In addition, seven of nine MM patients with complex chromosomal karyotype had concurrent plasmacytoma. Conclusion Although the limitation of retrospective study design and the small sample size exists, our findings indicate that the coexistence of complex chromosomal abnormality, probably which reflects aggressive disease status like extraosseous or extramedullary disease, could be associated with poor prognoses of MM patients with high-risk CA.

The aim of this study was to evaluate the value of scheduled imaging for patients who achieved first complete remission after CHOP-like chemotherapy plus rituximab. In this retrospective cohort study, we included 759 patients newly diagnosed with de novo diffuse large B-cell lymphoma (DLBCL) at the Cancer Institute, Japanese Foundation for Cancer Research. Relapsed patients were divided into two groups based on method of diagnosis: clinical symptoms (symptom group, n = 57) or scheduled imaging (imaging group, n = 27). Our primary goal was to compare overall survival and relapse-free survival between the two groups. No significant difference in outcomes was found between the symptom and imaging groups. Median overall survival [7.5 years; 95% confidence interval (CI) 4.0–9.7 vs. 9.1 years; 95% CI 2.7 to not reached; P = 0.747), and median relapse-free survival (1.8 years; 95% CI 1.4–2.5 vs. 2.4 years; 95% CI 1.2–4.4; P = 0.108). Surveillance imaging in patients with DLBCL who achieved first complete remission did not demonstrate an advantage in terms of overall survival or relapse-free survival.

Introduction: Recently cell-free DNA (cfDNA) genotyping analysis has been utilized as a non-invasive procedure for detecting tumor specific genes or clarifying gene mutations instead of tumor sample biopsies. In diffuse large B-cell lymphoma (DLBCL), cfDNA analysis has been proceeding and the relationships between somatic gene mutation and the disease status have been considered. We retrospectively analyzed somatic gene mutations in DLBCL and examined the correlation between mutant genes and clinical outcomes by using serum cfDNA samples. Patients and Methods: 50 patients newly diagnosed with DLBCL (including 4 patients mixed with follicular components) in our institute between March 2016 and March 2017 were enrolled in this study. All cases were sub-divided into germinal center B-cell (GCB) or non-germinal center B-cell (NGC) through immuno-staining, as CD10, bcl-6, and MUM-1 as Hans algorithm with biopsied tumor specimen. The stage at diagnosis and evaluation of treatment effects were assessed by PET-CT scan and bone marrow aspiration. All patients were treated by R-CHOP-like regimens with or without radiation. The serum samples from the patients were obtained before treatment and the cfDNA was extracted from the serum using a Maxwell RSC cfDNA Plasma kit. Using genomic DNA derived from cfDNA, multiplex polymerase chain reaction (PCR) was performed, and a sequence library was then constructed with an Ion Custom Amplicon panel. The panel for the sequence library was designed using an Ion AmpliSeq DesignerTM. 121 targeted genes were selected. The genomes were sequenced using the Ion ProtonTM System. We compared the validation of the sequence results dependent on the characteristics and prognoses of the patients. Connections between each gene mutation and clinical features were assessed using Fisher's exact test. Mann-Whitney U test was used for evaluating factors associated with the number of gene mutations. Survivals were estimated by the Kaplan-Meier method and differences were compared using the log-rank test. This protocol was approved by the institutional review board and the Genomic Review Board of the Japanese Foundation for Cancer Research. Results: Median age was 65.4 years old (range 33-83), 27 patients were male and 23 were female. The stage of Ⅲ or Ⅳ were 17 (34%), IPI high or high intermediate were 17 (34%), and 20 (40%) had LDH>ULN. 27 patients (54%) were GCB and 23 (46%) were NGC. With a median follow up was 26.6 months (range 6-35). Factors affecting both shorter overall survival (OS) and progression-free survival (PFS) were LDH>ULN (P=0.037 and P Discussion and Conclusion: This study showed serum cfDNA could be used as an alternative resource for analysis by tumor specimen. Our results indicated that TP53 mutation occurred in latter period undergoing multistep genetic variation and it showed the tendency that multistep mutations were related to poor prognosis. Interestingly, relative rate in TP53 mutation accompanied by CRBN mutation was high. In some reports, it was described that deletion p53 caused drug resistance including immunomodulator which targets CRBN in multiple myeloma cases. Zijun Y et al mentioned CRBN expression correlated with favorable prognosis in DLBCL with wild type TP53. Further studies are warranted to confirm the relationships between TP53 and CRBN mutations and its prognosis of DLBCL. Disclosures Mishima: Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Yokoyama:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Nishimura:Celgene K.K.: Honoraria; Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Hatake:Takeda Pharmaceutical Co.,Ltd.: Honoraria; Celgene K.K.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding. Terui:Bristol-Myers Squibb, Celgene, Janssen, Takeda, MSD, Eisai, Ono, and Chugai-Roche Pharmaceuticals Co.,Ltd.: Honoraria; Bristol-Myers Squibb K.K.: Research Funding.

Introduction: Cell-free circulating DNA (cfDNA) and its genetic mutations have been studied as a non-invasive tool to obtain clinical information in malignant lymphoma. We analysed serum cfDNA concentrations in lymphoma patients and investigated its gene mutation profile in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Methods: Serum samples from lymphoma patients diagnosed at our institution between 2016-2017 were obtained at the time of initial diagnosis. Serum samples of 10 healthy individuals were used as control. cfDNA was extracted using Maxwell RSC cfDNA Plasma Kit (Promega), and concentration was measured by Quantus Fluorometer (Promega). The serum concentration level in each subtype of lymphoma was compared to control using Mann-Whitney U test. Furthermore, progression free survival (PFS) was compared between those with and without elevated cfDNA concentrations using Kaplan-Meier method. We also assessed factors associated with elevated cfDNA. Using cfDNA, multiplex PCR was performed, then a sequence library constructed with an Ion Custom Amplicon panel. The panel for the sequence library was designed using the Ion AmpliSeq DesignerTM . Genomes were sequenced for the selected 121 target genes using the Ion ProtonTM System. Frequencies of each mutation were compared amongst DLBCL, FL, and DLBCL + FL using Kruskal-Wallis test. Results: We analysed 114 patients with newly diagnosed lymphoma (DLBCL n=63, DLBCL combined with FL n=8, DLBCL combined with extranodal marginal zone B cell lymphoma (MALT) n=1, FL n=20, FL/MALT n=1, Burkitt lymphoma (BL) n=1, MALT n=8, Mantle cell lymphoma (MCL) n=3, Low-grade B cell lymphoma n=2, Hodgkin lymphoma (HL) n=4, Peripheral T cell lymphoma (PTCL) n=3), as well as control (n=10). The median cfDNA concentration in all lymphoma patients was 55.8ng/ml (range 6.2-1220.0ng/ml), which was significantly higher than that for control (median 7.5ng/ml, range 4.4-14.1ng/ml; p40ng/ml) was significantly associated with shorter PFS in patients with DLBCL (PFS at 24 months; 100% vs. 79%, p=0.03). For this group of patients, B-symptoms (p=0.04), bulky masses (p=0.03) or non-germinal center B-cell like (GCB) subtype (p=0.02) were found to correlate with elevated cfDNA levels. We then analysed 77 cases with available genetic mutation data (DLBCL n=46, FL n=23, DLBCL + FL n=8). The frequencies of each mutation for each subtype are shown in Figure 1. Gene mutation profiles were similar in each group; CREBBP, EGR1, HDAC4, HDAC6, JMJD1C, and KDM3B being some of the most frequently mutated genes. PCLO and KDM1A mutations were more frequently found in DLBCL compared to FL. Discussion and Conclusion: Serum cfDNA concentration is predictive of certain clinical characteristics and may be used as one of the predictors for survival outcomes in DLBCL. PCLO encodes protein that is part of the presynaptic cytoskeletal matrix and although its role in lymphoma is unclear, its mutation has previously been reported. KDM1A encodes histone demethylase, which has been widely discussed as a target for cancer therapy, yet its role in lymphoma is poorly understood. Further studies with a larger sample size and longer follow up period are warranted to better understand the role of cfDNA gene mutations in obtaining clinical information. Figure 1 Disclosures Mishima: Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Yokoyama:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Nishimura:Celgene K.K.: Honoraria; Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Hatake:Celgene K.K.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; Takeda Pharmaceutical Co.,Ltd.: Honoraria. Terui:Bristol-Myers Squibb, Celgene, Janssen, Takeda, MSD, Eisai, Ono, and Chugai-Roche Pharmaceuticals Co.,Ltd.: Honoraria; Bristol-Myers Squibb K.K.: Research Funding.

Introduction)Somatic mutations in multiple myeloma (MM) are strongly related to the clinical outcome and clonal evolution over the clinical course, and are a major problem. From a clinical viewpoint, although numerous novel drugs have been utilized, achieving long-lasting and complete remission remains difficult. Recent studies have elucidated the mutated genes using next-generation sequencing, and have examined how clonal change can be acquired in myeloma. In this study, we traced the transition of the somatic mutations of bone marrow tumor cells in patients with MM over a long-term follow-up. Furthermore, we compared the somatic mutations found in serum cell-free DNA (cfDNA) and mutated genes obtained from bone marrow myeloma cells. Material and Methods)Patients diagnosed with multiple myeloma who provided written informed consent to participate in the study were enrolled. Patients were treated by immuno-chemotherapy with or without radiation between 2000 and 2017 at our institute. Bone marrow aspiration and biopsy were performed at the time of diagnosis and upon disease progression. Around the time of bone marrow aspiration, serum was obtained from a peripheral blood sample for cfDNA analysis. Myeloma cells were separated from bone marrow samples with MicroBeads of CD138 antibody and genomic DNA was extracted. The peripheral blood samples derived from myeloma patients. The cfDNA was extracted from the serum using a Maxwell RSC cfDNA Plasma kit. Using genomic DNA derived from cfDNA and bone marrow, multiplex polymerase chain reaction (PCR) was performed, and a sequence library was then constructed with an Ion Custom Amplicon panel. The panel for the sequence library was designed using an Ion AmpliSeq DesignerTM. 126 targeted genes were selected. The genomes were sequenced using the Ion ProtonTM System. This protocol was approved by the institutional review board and the Genomic Review Board of the Japanese Foundation for Cancer Research. Result)We followed 7 patients' long term-clinical course and the transition of mutations (8.5 year average). The expression of myeloma driver genes, such as RAS, BRAF, and MYC, were not critical. We did, however, detect a relationship between an increase in the dominant mutated gene, such as TP53, DIS3, FAM46C, KDM6B, and EGR1 and poor prognosis in patients with myeloma. Next, we calculated the cfDNA concentrations from 34 cases. The cfDNA concentrations were significantly higher than 10 control cases (average 62.0 ng/mL (0-200 ng/mL) and 8.18 ng/mL (4.3-14.1 ng/mL), P=0.0046). The 2.5 year-progression free survival (PFS) during the first treatment of MM were tend to be poorer in the group with cfDNA>50 ng/mL (72.9%) than the group with cfDNA Discussion)Our data demonstrate the importance of the long-term follow-up of somatic mutations during the clinical course of myeloma. Serum cfDNA is a useful alternative source for detecting somatic mutations in MM patients during long-term follow-up. Disclosures Mishima: Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Yokoyama:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy. Nishimura:Chugai-Roche Pharmaceuticals Co.,Ltd.: Consultancy; Celgene K.K.: Honoraria. Hatake:Celgene K.K.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding; Takeda Pharmaceutical Co.,Ltd.: Honoraria. Terui:Bristol-Myers Squibb K.K.: Research Funding; Bristol-Myers Squibb, Celgene, Janssen, Takeda, MSD, Eisai, Ono, and Chugai-Roche Pharmaceuticals Co.,Ltd.: Honoraria.

Introduction; The prognosis of relapsed and refractory DLBCL (RR-DLBCL) after R-CHOP therapy is poor and the more than half of these cases had no cure. Autologous peripheral blood stem cell transplantation (auto-PBSCT) raises the survival rate about 20%, however many patients cannot reach the transplantation. The poor prognostic factors in RR-DLBCL have not been cleared yet. MYC/IgH translocations induced poor prognosis of DLBCL, especially double hit DLBCL is independent category in WHO 2016 criteria. However, in RR-DLBCL, the impact of MYC/IgH translocation had not been cleared yet. In this study, we studied the expression of MYC/IgH translocation in RR-DLBCL cases and analyzed the relationships with the prognosis by retrospectively. Methods; We studied the translocations of MYC and BCL-2 by FISH analysis RR-DLBCL cases from 2006 to May 2017 in our institute. The cells were obtained from the biopsy samples at the first diagnosis and relapse or refractory status. The cells have been fixed by carnoy solution. After hybridizing with each probe, the 100 cells or more were analyzed by In Cell Analyzer 6000 and the positive levels were determined as 5% or more in both MYC and BCL-2. Additionally pathological review and clinical status were studied among these cases, retrospectively. All cases are treated by R-CHOP at diagnosis and followed by salvage therapy after relapse with or without auto-PBSCT. This study protocol was approved in our institutional ethical review board. Results; Within 46 RR-DLBCL, 24 cases were negative for MYC translocation and 22 were positive. All MYC-positive cases were translocated with IgH except one case and the 9 cases (47.8%) were BCL2-positive. The median age was 62.4 (40-83) in MYC-negative and 62.6 (44-82) in MYC-positive cases. GC type was 11 (45%) and 9 (40.9%), and High IPI cases were 8 (33.3%) and 12 (54.5%) in MYC-negative and positive cases respectively. In these RR-DLBCL, the 5-year Overall survival (OS) was inferior in MYC-positive group (79.4%, 95% CI; 53.5-91.8%) compared to MYC-negative group (56.2%, 95%CI; 32.1-74.7%) (P=0.0414). There was no significant difference in progression free survival (PFS). There were no statistically significant differences in overall response rate (ORR), OS and PFS after second therapy between MYC-positive and negative group. The death cases were 6 (25%) and 11 (50%), respectively (P=0.079). By the pathological analysis, the transformed DLBCL cases from follicular or indolent lymphoma were significantly more in MYC negative group (12; 50%) than in MYC positive group (4; 18.1%) (P=0.024). In the transformed DLBCL, at the first relapse, 2nd biopsy detected heterogeneous pattern, such as the only indolent lymphoma, DLBCL or contamination of both type. In such cases, at the 2nd relapse, the pathological diagnoses had changed again. OS and PFS were significant superior in transformed DLBCL than de-novo DLBCL after second therapy. 2-year OS were 59.0%(95%CI 37.9-75.1%) and 92.9%(59.1-99.0%) (P=0.00474) and PFS were 16.13 and 49.43 moths (95% CI was 10.4 to 20.1 months and 16.1 to 63.7 months; P=0.00063), in transformed FL and de novo-DLBCL, respectively. The multivariate analysis identified transformed DLBCL as independent prognostic factor for both PFS and OS. Also, in MYC positive group, transformed DLBCL cases were superior to de-novo DLBCL for both OS (17.5 months vs. not yet reached, P=0.0353) and PFS (13.3 vs. 63.3moths, P= 0.0353) respectively. Discussion and conclusion; From our results, it was suggested MYC-positive is still poor prognostic factor of overall survival in RR-DLBCL. However, RR-DLBCL contaminated transformed DLBCL especially in the MYC-negative group. After 2nd therapy, the transformed DLBCL were related to good prognoses compared to de-novo-DLBCL, in also MYC-positive group. We can consider that treatment strategy of transformed DLBCL were should be separated from de-novo DLBCL at the relapse, then MYC-positive transformed DLBCL still possesses for indolent character. Disclosures Mishima: Chugai pharmaceutical inc, Roche: Other: commissioned work. Yokoyama:Chugai pharmaceutical inc, Roche: Other: commissioned work. Nishimura:Chugai pharmaceutical inc, Roche: Other: commissioned work. Terui:Celgene: Honoraria; Janssen Pharmaceutical KK: Honoraria; Takeda pharmaceutical: Honoraria; Novartis pharma: Honoraria; Bristol myers Squib: Honoraria.

The transformation of indolent lymphoma is biologic event leading to aggressive lymphoma status. As same de-novo diffuse large B cell lymphoma (DLBCL), the outcome of DLBCL with transformation has improved by the use of rituximab contained therapy. However, the effects of rituximab maintenance for DLBCL with transformation remain unknown. We performed a retrospective analysis to evaluate the efficacy of rituximab maintenance for DLBCL with transformation. We studied patients newly diagnosed as transformed DLBCL from March 2005 to November 2017 in our institution. The pathological diagnosis was performed based on morphological and immunohistochemical analyses. Transformed DLBCL was defined in our study as a coexistence with components of follicular lymphoma (FL) or MALT lymphoma and DLBCL in a biopsied tissue at the diagnosis. Almost all patients were treated with R-CHOP chemotherapy (2 were treated by radiation with or without rituximab therapy, one was R-ICE chemotherapy). 15 patients received rituximab maintenance therapy for two years after achieving good PR or more by first therapy. PET-CT was used to evaluate the stage at the diagnosis and the response after therapy. The statistical analyses of characteristics of patients were performed by Fisher's exact test. The survivals were calculated by the Kaplan Meier method, and statistical analysis were performed by log rank test. Factors affecting OS and PFS were evaluated using Cox proportional hazard model. We analyzed 52 transformed patients. Median age was 64 years old (range 43-87), 35 patients were male (67%) and 17 were female (33%), 44 (84%) were transformed from FL and 8 (16%) were from MALT lymphoma. Germinal center B cell (GCB) type were 35 (67%) and activated B cell (ABC) were 16 (30%). An ECOG performance status (PS) ≧2 was only 1 patient (1.9%). 3 (5.7%) had B symptoms, 16 (30%) had LDH ≧ULN, 28 (53%) had stage of Ⅲ or Ⅳ, 5 (9.6%) had bone marrow invasion, 13 (25%) had IPI score ≧3, and 26 (50%) had one or more extranodal diseases. There were no significant differences in characteristics between rituximab maintenance group and no maintenance group. After induction therapy, CR was achieved in 48 (92%) and PR was 4 (8%). With a median follow up of 66 months (range 7-143), 5-year OS and 5-year PFS were 95.6% (range 83.3-98.9) and 71.7% (range 55.4-83.0) respectively. There were not statistically significant in OS and PFS between the rituximab maintenance group and the observation group (5-year OS: 100% vs 93.6%, p=0.0895, 5-year PFS: 100% vs 65.7%, p=0.0792). However, subgroup analyses showed that rituximab maintenance group was significantly superior to no maintenance group in PFS in the cases of stage III or more (5-year PFS 100% vs 30.7%, p=0.0137), males (100% vs 56.7%, p=0.0436), and GCB type (100% vs 60.0%, p=0.029). The rituximab maintenance (P=0.0356: HR 0.20; 95% CI 0.046-0.899) was indicated as the clinical parameters related to PFS by multivariate analysis. Generally, DLBCL with transformation have poor prognosis. There are several previous reports about rituximab maintenance for patients with aggressive B-cell lymphoma, which concluded that rituximab maintenance in first remission didn't provide an advantage to OS and PFS. NHL 13 trial demonstrated statistical benefit of rituximab maintenance for males and low IPI group. Regard to transformed lymphoma, the study for maintenance of rituximab was really few. Hany R et al reported the outcome of patients with transformation that rituximab maintenance post R-CHOP and the number of maintenance rituximab cycles were associated with better PFS. Our data provided that rituximab maintenance was effective in transformed DLBCL with regard to prolonged PFS in subgroups of progressive stage, men, and GCB. In conclusion, from our study it was suggested that rituximab maintenance therapy have possible to improve outcomes for DLBCL with transformation. Disclosures Mishima: Chugai pharmaceutical inc, Roche: Other: commissioned work. Yokoyama:Chugai pharmaceutical inc, Roche: Other: commissioned work. Nishimura:Chugai pharmaceutical inc, Roche: Other: commissioned work. Terui:Takeda pharmaceutical: Honoraria; Janssen Pharmaceutical KK: Honoraria; Celgene: Honoraria; Bristol myers Squib: Honoraria; Novartis pharma: Honoraria.

Background: In patients with diffuse large B-cell lymphoma (DLBCL), adequate follow-up is required with the improvement of prognosis. The efficacy of scheduled imaging for patients with DLBCL who achieved complete response (CR) is discussed. The possibility to avoid surveillance imaging have been reported, although most studies are based on a small number of cases. The NCCN guideline version 4.2018 recommend not to perform scheduled imaging routinely for follow-up, or only for patients with stage III/IV. However, there is no strong evidence of supporting the inferiority of scheduled imaging. It is possible that some patients might benefit from scheduled imaging. Methods: We investigated patients with de novo DLBCL who were diagnosed in The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Japan from 5 January 2013 to 31 May 2016 retrospectively, to conduct a sampling of first relapsed patients after CR. Patients who achieved CR after salvage therapies were included. Patients who received first-line therapy without rituximab because of non-approved use at the time were excluded. Relapse diagnosis without pathological proof were permitted. Eligible patients had a minimum of 2 years follow-up. All data were updated 17 July 2018. Overall survival (OS) was censored at the last date of follow-up. Relapsed patients were divided into 2 groups according to a momentum of diagnosis, clinical symptoms (symptom group) or scheduled imaging (imaging group). Clinical symptoms are defined as subjective complaint, physical exam finding and blood test abnormality. Imaging modality includes echography, computed tomography (CT), magnetic resonance imaging and positron emission tomography/CT. The Hans classifier, using CD10, BCL6, and MUM1 immunohistochemistry, was used to categorize as germinal center B-cell-like (GCB) or non-GCB. Fischer's test was used for comparative between the symptom group and imaging group, Kaplan-Meier test for calculate survivals, the logrank test for statistical analysis of OS, event-free survival (EFS) and survival parameters. All statistical analyses were performed with EZR software. Results: A total of 759 patients were identified as de novo DLBCL. Then 630 achieved CR, 527 had maintained CR and 103 relapsed. Among the 103 cases, 7 patients were excluded because of lack of some data. Eventually, 96 patients with first relapse were enrolled in this analysis. Relapse was confirmed pathologically in 85% (82/96) cases. Only in the symptom group, all 7 cases were not received biopsy because of central nervous system involvement. Most patients were scheduled to perform imaging every 6 months. We divided the 96 first relapsed patients into 2 groups by the momentum of relapse diagnosis. The median follow-up duration was 56.1 months. While 67% were detected by clinical symptoms, 33% had relapse diagnosis by scheduled imaging, and their characteristics are summarized in Table 1. Significant differences in the outcome were not found between the symptom group and the imaging group: 4-year OS (57%, 95% confidence interval [CI] 0.44-0.68 vs. 4-year OS: 63%, 95% CI 0.44-0.78; P = 0.517), 4-year EFS (20%, 95% CI 0.12-0.31 vs. 28%, 95% CI 0.14-0.44; P = 0.163), and median OS after first relapse (33.0 months vs. 55.4 months; P = 0.512), respectively (Fig 1). In the symptom group, indications were lymph node swelling (38%), neurological symptoms (20%), subcutaneous mass (17%), head and neck discomfort (10%), B symptom (6%) and blood test abnormality (3%). Univariate analysis revealed that only the existence of B symptoms at first diagnosis was significant for OS (P = 0.0361). Multivariate analysis using stepwise multiple logistic regression also demonstrated that the existence of B symptoms at first diagnosis to be the single independent factor of OS (P = 0.0402). In the imaging group, univariate analysis revealed that the existence of B symptoms at first diagnosis was significant for OS (P = 0.0241). There was no significant difference in OS between patients with stage I/II and stage III/IV in the 96 relapsed patients (P = 0.618). Conclusion: These results indicate that routine image surveillance in DLBCL patients during their first CR does not improve OS and EFS. However, B symptoms at first diagnosis was a significant factor for OS in both the symptom and imaging group, Patients with B symptoms at diagnosis might receive a benefit of image surveillance. Disclosures Nishimura: Chugai pharmaceutical inc, Roche: Other: commissioned work. Mishima:Chugai pharmaceutical inc, Roche: Other: commissioned work. Yokoyama:Chugai pharmaceutical inc, Roche: Other: commissioned work. Terui:Celgene: Honoraria; Bristol myers Squib: Honoraria; Janssen Pharmaceutical KK: Honoraria; Takeda pharmaceutical: Honoraria; Novartis pharma: Honoraria.

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL). Typically, the dose of rituximab is 375 mg/m2; data obtained from recent clinical trials about the pharmacokinetics of rituximab showed that elderly women have a better outcome than elderly men and a more favorable pharmacokinetics of rituximab than all other patients with DLBCL. Therefore, optimization of the dose and schedule of rituximab is required for the subpopulation of patients with DLBCL that show a fast clearance of rituximab. The metabolism of rituximab, which is mostly excreted through the kidneys, is not completely understood thus far. Renal function, which is determined using creatinine clearance (CCr), at the time of administration may affect the clearance of rituximab, and thus, the therapeutic outcomes. We examined the association between the rate of CCr and survival outcome in patients with DLBCL treated with R-CHOP. We evaluated 653 patients with newly diagnosed de novo DLBCL, excluding those with transformed DLBCL, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from January 2005 to December 2015. All patients were treated with R-CHOP or modified regimens. CCr was calculated using the Cockcroft-Gault formula. Tumour staging and response assessment were performed using the revised response criteria for malignant lymphoma and the International Conference on Malignant Lymphomas Imaging Working Group by using positron emission tomography-computed tomography and bone marrow biopsy. Progression-free survival (PFS) and overall survival (OS) were defined as the time from the date of initiation of R-CHOP to the date of disease progression, relapse, last follow-up, or death from lymphoma. Deaths due to reasons other than lymphoma were censored. PFS and OS were estimated using the Kaplan-Meier method, and the differences were compared using the log-rank test. The Cox proportional hazards regression models were used to identify the prognostic factors to predict the PFS and OS. A total of 653 patients with DLBCL were met the inclusion criteria, and the median follow-up for survival was 64 months. Our results showed that 133 (20.3%) patients had a CCr rate less than 60 mL/min. Patients with a low rate of CCr were older, had an advanced stage of DLBCL, extranodal disease, high levels of lactate dehydrogenase (LDH), and high proportion of non-germinal cell (GC) subtype, which are indicators of a poor prognosis. Therefore, patients with a lower rate of CCr showed poorer PFS (5-year PFS 74.2% vs. 80.8%, p = 0.13) and OS (5-year OS 77.1% vs. 86.9%, p=0.013). Further, we performed subgroup analysis according to CCr using the revised International Prognostic Index (R-IPI), which includes of age >60 years, stage III/IV disease, elevated LDH levels, performance status ≥ 2, more than one extranodal site of disease. Although all prognostic groups did not show a significant difference depending on the CCr, the groups with very good and good prognosis showed superior PFS in a low rate of CCr group than high rate of CCr group (Figure 1). The results of subgroup analysis for OS were similar to those observed for PFS. Thus, patients with very good and good prognosis determined using R-IPI may be affected by the subtle difference in the clearance of rituximab, whereas those with poor prognosis may not be affected by this difference. Results of multivariate analysis for PFS and OS showed that a low rate of CCr was not a significant prognostic factor. Thus, our results showed that although CCr may be a factor for clearance of rituximab, no significant association exists between the rate of CCr and survival. Our findings suggest that modification of the dose of rituximab depending on CCr is not recommended for improving survival. Further studies are required to establish an optimal dose and schedule of rituximab in all subgroups of patients with DLBCL. Disclosures Nishimura: Chugai Pharmaceutical Co., Ltd.: Other: commissioned work. Mishima:Chugai pharmaceutical inc, Roche: Other: commissioned work. Yokoyama:Chugai pharmaceutical inc, Roche: Other: commissioned work. Terui:Bristol myers Squib: Honoraria; Celgene: Honoraria; Janssen Pharmaceutical KK: Honoraria; Takeda pharmaceutical: Honoraria; Novartis pharma: Honoraria.

Introduction The international prognostic index (IPI) was a most common prognostic score in patients with aggressive non-Hodgkin lymphoma. Therefore, rituximab improved OS in patients with diffuse large B-cell lymphoma (DLBCL), revised IPI (R-IPI) was suggested. Although, the 5-year OS is higher than 50% in patients of high risk R-IPI. National Comprehensive Cancer Network published an enhanced IPI (NCCN-IPI) for improving risk stratification. However, NCCN-IPI didn't enough evaluate clinical and disease characteristics, for example beta-2-microglobulin (B2MG), cell of origin, albumin, soluble interleukin-2 receptor (sIL-2R). Aim of this study is to evaluate clinical and disease prognostic factor in patients with DLBCL. Methods We retrospectively analyzed 647 patients who were newly diagnosed de novo DLBCL and treated with R-CHOP in our hospital from January 2005 to December 2016. We excluded primary central nervous system lymphoma and transformed from low grade B-cell lymphoma. Median follow-up time is 58.5 months (range; 2-160 months.). We collected data of blood and imaging test before chemotherapy. The patient's baseline clinical and disease characteristics included age, Ann Arbor stage, serum albumin, bulky, B symptoms (defined as recurrent fever, night sweats, or >10% weight loss), B2MG, cell of origin, cluster of differentiation (CD) 5 positive, serum C-reactive protein (CRP), ECOG performance status (PS), ferritin, gender, lactate dehydrogenase (LDH), sIL-2R, monocyte, number and site of involvement extranodal. We evaluate over 60-years old, advance stage (Ann Arbor stage Ⅲ-Ⅳ) and more than PS 2. We defined the cut-off value of B2MG, CRP, ferritin, sIL-2R, monocyte and albumin by using receiver operating characteristic curves. LDH was over the upper limit of normal. Cell of origin was classified by Hans' algorithm. CD 5 was evaluated by immunohistochemistry. The univariate analyses of between factors and OS was used in univariate of log-rank test. And the multivariate analysis was used cox proportional hazards regression analysis. Results The patient's median age was 65 years old (range 17-90 years old.). The cut-off value of B2MG is ≧2.23 mg/L, CRP is ≧0.4 mg/dl, ferritin is ≦250 ng/ml, sIL2-R is ≧1000 U/mL, monocyte is ≧608 /μL and serum albumin is ≦3.4 g/dl. In the result of univariate analysis, age, stage, albumin, B symptoms, B2MG, CD5, CRP, PS, ferritin, LDH, sIL-2R, monocyte, nonGCB, the number of extranodal sites (>1) and the involvement of bonemarrow, liver, lung, muscle, skin and pancreas affected OS. In multivariate analysis, the worse prognostic factors were age (Hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.27-3.57, p Albumin, B2MG and sIL-2R weren't included prognostic score of IPI, R-IPI and NCCN-IPI. In order to validate we developed prognostic score consisting of 5 factors (age, PS, B2MG, sIL-2R and albumin). And compared with NCCN-IPI in our data. We categorized patients into 4 risk groups: low (0 factor), low-intermediate (1 factor), high-intermediate (2 or 3 factors), high (4 or 5 factors). The low risk of 5-year OS was 91.5%, low-intermediate risk was 86.2%, high-intermediate risk was 72.3% and high risk was 37.4%. The low risk of NCCN-IPI was 95.1%, low-intermediate was 86.2%, high-intermediate was 68.8% and high was 50.6%. The absolute difference in the 5-year OS between low and high risk groups was 54.1% with our study prognostic score compared with 44.5% with NCCN-IPI in our study. Conclusions Our study suggest that B2MG, sIL-2R and serum albumin are significant prognostic factors in patients with DLBCL in the rituximab era. Figure. Figure. Disclosures Yokoyama: Chugai pharmaceutical inc, Roche: Other: commissioned work. Mishima:Chugai pharmaceutical inc, Roche: Other: commissioned work. Nishimura:Chugai pharmaceutical inc, Roche: Other: commissioned work. Terui:Novartis pharma: Honoraria; Takeda pharmaceutical: Honoraria; Janssen Pharmaceutical KK: Honoraria; Celgene: Honoraria; Bristol myers Squib: Honoraria.