Revised International Prognostic Index Research Articles

A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results

A Phase I Study of CC-90002, a Monoclonal Antibody Targeting CD47, in Patients with Relapsed and/or Refractory (R/R) Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndromes (MDS): Final Results

The Clinical Impact of Modified Barthel Index in Elderly Patients over 60 Years with Diffuse Large B-Cell Lymphoma

[Introduction]Modified Barthel Index (MBI) is widely used to measure performance in activities in daily living (ADL), especially in elderly patients. MBI consists of 10 items: feeding, personal hygiene (grooming), bathing, dressing, toilet transfer, bladder control, bowel control, chair/bed transfers, stair climbing, and ambulation. A total score ranges from 0 to 20. MBI has been studied in several types of cancer which is correlated with prognosis. However, the prognostic role of MBI in diffuse large B-cell lymphoma is still unknown. The study aims to investigate the predictive role of MBI in elderly patients over 60 years with DLBCL. [Methods]This retrospective study included elderly DLBCL patients over 60 years treated at our institution between 2009 and 2018. MBI score of each patient was evaluated at diagnosis. Receiver operator characteristic (ROC) curve was used to generate a cut off value for MBI. Kaplan-Meier method and univariate, multivariate analysis by Cox proportional hazards model were performed to assess the prognostic influence of the factors including Stage, Revised International Prognostic Index score (R-IPI), Performance status (PS), Extra-nodal Site Involvement (ESI), Lactate Dehydrogenase (LDH), Soluble Interleukine-2Receptor (sIL-2R), Albumin, B symptoms and MBI. The study protocol was approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki. [Results]A total of 187 patients were included in the analysis. There were 102 males and 85 females, with a median age of 77 (range: 61-93). The median follow-up time was 39 months. The optimal MBI cutoff value for predicting 3-year survival was determined by ROC analysis to be 14.Patients with low MBI scores (< 14) had significantly shorter overall survival (OS) than those with high MBI scores (≥ 14) (3-year OS, 14.2 % vs. 65.2 %, p < 0.001). Among 163 patients receiving chemotherapy, patients with low MBI scores had shorter OS than those with high MBI scores (3-year OS, 21.2 % vs. 66.4 %, p < 0.001). In multivariate analysis, parameters having independent adverse significance for OS were: Low MBI (< 14) (p < 0.001, HR 2.49), PS ( ≥ 2) (p=0.04, HR 1.84). [Conclusion]In the present study we demonstrated that Low MBI was deeply associated with poor outcome in elderly patients with DLBCL. In particular, our data proved that a low MBI is an independent prognostic factor for survival in elderly patients with DLBCL. These results suggest that Low MBI may have an important role in DLBCL and may be also a useful prognostic marker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. Disclosures No relevant conflicts of interest to declare.

Interim Serum Soluble Interleukin-2 Receptor Levels Are Strongly Associated with Prognosis in Newly Diagnosis DLBCL Patients

<Background> Serum soluble interleukin-2 receptor (sIL2R) levels are often measured to evaluate the state of lymphoma. The serum sIL2R level at diagnosis has been reported to be correlated with the prognosis of diffuse large B cell lymphoma (DLBCL) patients treated with the R-CHOP regimen. However, it is unclear whether interim sIL2R levels are associated with prognosis in DLBCL. Here, we analyzed the prognostic impact of interim serum sIL2R levels in DLBCL. <Patients and Methods> We retrospectively examined data for DLBCL patients who started receiving chemotherapy at the Japanese Red Cross Society Kyoto Daini Hospital between January 2012 and December 2018. All of the patients received R-CHOP-like regimens (rituximab plus pirarubicin or adriamycin, cyclophosphamide, vincristine, and prednisolone). The interim sIL2R level (I-IL2R) was defined as the value measured after the third chemotherapy cycle. I-IL2R levels of >700 U/ml were regarded as positive. The primary endpoints of this study were progression-free survival (PFS) and overall survival (OS). The unadjusted probabilities of PFS and OS were estimated using the Kaplan-Meier method. The log-rank test and multivariate Cox regression analysis were used to assess the prognostic value of each clinical variable. <Results> In total, 102 patients were enrolled. The patients' median age was 73.5 years (range, 35-88), 58 patients (56.9%) were male, and 52 (51.0%) had poor revised International Prognostic Index scores. The median follow-up time was 25.2 months (range, 3.7-88.6). Twenty-three patients (22.5%) were I-IL2R-positive (>700 U/ml). Univariate analysis revealed that I-IL2R-positivity was associated with a poor prognosis. The 3-y PFS rates of the I-IL2R-negative (<700 U/ml) and I- IL2R-positive (>700 U/ml) patients were 60.4% (95% confidence interval [95%CI], 46.2-71.9) and 37.5% (95%CI, 15.7-59.4; p<0.001, log-rank test), respectively, and their 3-y OS rates were 82.2% (95%CI, 69.7-89.9) and 37.4% (95%CI, 13.8-61.4; p<0.001, log-rank test), respectively. Multivariate analysis confirmed that the I-IL2R level is independently associated with prognosis. <Conclusion> The I-IL2R level of >700 U/ml patients had poor prognosis. The I-IL2R level can be used to predict the outcomes of DLBCL patients. IL2R levels should be measured during chemotherapy, and I-IL2R-positive patients could be targeted with high-dose or novel therapies. As this study was based on a retrospective analysis and involved a small cohort and a limited follow-up period, further studies are needed to confirm the prognostic impact of I-IL2R. Figure Disclosures No relevant conflicts of interest to declare.

Is triple-positive serology for Epstein-Barr virus (VCA-IgG, VCA-IgM, EBNA-IgG) a specific feature of angioimmunoblastic T-cell lymphoma?

We assessed the frequency of triple-positive serology (viral capsid antigen [VCA]-immunoglobulin G [IgG], VCA-immunoglobulin M, Epstein-Barr nuclear antigen-IgG) for Epstein-Barr virus (EBV) in a small number of patients with angioimmunoblastic T-cell lymphoma (AITL) at disease onset. Nine patients with newly diagnosed AITL were retrospectively enrolled in the present study. For all of them, EBV serology data were available. Of 9 patients, 7 (77.7%) had a triple-positive serology (VCA-IgG, VCA-IgM, EBNA-IgG ) for EBV. These patients were characterized by bone marrow involvement, high incidence of thrombocytopenia, and poor prognosis according to Revised International Prognostic Index and Prognostic Index for Angioimmunoblastic T-cell Lymphoma scores. Assessment of both viremia and serology for EBV could be useful in patients with clinical and laboratory data suggesting lymphoma diagnosis; furthermore, although our data need to be validated in a larger cohort of patients, triple positivity for EBV serology might help to direct the diagnosis toward AITL.

Useful prognostic tools based on complete blood cell counts in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma. Three prognostic factors are widely used in DLBCL: International Prognostic Index (IPI), Revised-IPI (R-IPI), and National Comprehensive Cancer Network-IPI (NCCN-IPI). We established a prognostic model using peripheral blood absolute lymphocyte/absolute monocyte counts ratio (LMR), hemoglobin, and platelet counts obtained from complete blood cell counts (CBC) data at diagnosis based on 214 cases of DLBCL who received more than one course of R-CHOP therapy at a single institution. The cutoff values for using the receiver operating characteristics (ROC) curve for LMR, hemoglobin, and platelet counts were 1.6, 100g/L, and 150×109 /L, respectively. Stratification was performed using the three factors (LMR<1.6, hemoglobin<100g/L, and platelet counts<150×109 /L). CBC Group 1 (none of the 3 factors) included 92 cases, CBC Group 2 (1 or 2 of these factors) included 108 cases, and CBC Group 3 (all 3 factors) included 11 cases. The 5-year OS rates were 78.2%, 60.9%, and 10.1%, respectively. In multivariate analysis, CBC Group 3 (hazard ratio, 2.9760; 95% confidence interval, 1.2670-6.991; P=.01) were prognostic factors for OS. CBC Group 3 had factors based on which the further stratification of the poor prognosis group into IPI high-risk and R-IPI poor-risk groups (P=.01, <.0001, respectively) was possible. In DLBCL, combination of three CBC parameters has the potential to be a useful prognostic tool.

Clinical features and survival of patients with T-cell/histiocyte-rich large B-cell lymphoma: analysis of the National Cancer Data Base

Using data from the National Cancer Data Base, 2010–2015, we examined characteristics and outcomes of T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL, N = 622) relative to unspecified diffuse large B-cell lymphoma (DLBCL-NOS, N = 91,588) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL, N = 2240). Socio-demographic characteristics of patients with THRLBCL resembled more NLPHL than DLBCL-NOS. Five-year overall survival in THRLBCL was 66% (95% confidence interval [CI], 60–71%). Adjusting for clinical and socio-economic covariates, THRLBCL was associated with better survival than DLBCL-NOS (adjusted hazard ratio, 0.80; 95%CI, 0.67–0.94). This association was similar in academic and community hospitals and consistent in a model stratified by the revised International Prognostic Index. Prognostic factors in THRLBCL included age, comorbidity index, and extranodal primary site, but not stage. Adjusted odds of prior NLPHL were 18.2 higher for THRLBCL (95%CI, 7.2–45.7) than DLBCL-NOS. These large-scale epidemiologic data support the relationship between THRLBCL and NLPHL, and suggest improved prognosis with modern rituximab-based immunochemotherapy.

PF320 VENOUS THROMBOSIS AND BASELINE C‐REACTIVE PROTEIN ARE INDEPENDENT PROGNOSTIC MARKERS IN DIFFUSE LARGE B‐CELL LYMPHOMA AND IDENTIFY A GROUP OF PATIENTS WITH SIGNIFICANTLY INFERIOR OUTCOMES

Background:The association between inflammation and cancer has been well described. C‐reactive protein (CRP) is one of the most commonly utilised inflammatory markers in clinical practice. Many studies have demonstrated that elevated CRP is an important prognostic factor in different types of cancer. Venous thromboembolism (VTE) is a common complication in patients with cancer and has also been associated with worse outcomes.Aims:The aim of our study is to verify whether the CRP at diagnosis and the presence of VTE are valid prognostic parameters in diffuse large B‐cell lymphoma (DLBCL).Methods:Data from patients with DLBCL treated with rituximab‐based chemotherapy between January 2008 and December 2018 were retrospectively evaluated. Only patients with CRP performed at baseline were included. Episodes of VTE confirmed by imaging studies that were present at diagnosis or occurred during initial therapy were identified. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were used to determine the best cut‐off value of CRP for survival. Kaplan‐Meier curves with log‐rank test and Cox regression were used to assess the impact of pre‐treatment CRP, VTE and other parameters on the overall survival (OS).Results:316 cases of DLBCL were identified during the study period; 16 patients (5.1%) were excluded because pre‐treatment CRP was not available. Three hundred patients were included in the study with a median follow‐up of 54.8 months (range 2.9–133.9 months) and median age of 66 years (range 18–97 years). One hundred and fifty‐two patients (50.7%) were female and 148 patients (49.3%) were male. The best cut‐off for CRP at diagnosis was 30 mg/L with an AUC of 0.72 (95% CI, 0.65–0.77, P &lt; 0.001). Elevated CRP levels (&gt;30 mg/L) were present in 159 patients (53.0%), while 141 patients (47.0%) had low CRP levels (≤30 mg/L). Thrombosis occurred in 12.7% of patients (39 events in 38 of 300 patients). Patients with a high CRP were more likely to have B symptoms (P &lt; 0.001), Ann Arbor Stage III or IV disease (P = 0.007), bulky disease (P = 0.003), higher ECOG performance scores (P &lt; 0.001), raised LDH levels (P &lt; 0.001), more extra‐nodal areas involved (P &lt; 0.001) and higher revised International Prognostic Index (R‐IPI) scores (P &lt; 0.001). Patients with thrombosis were more likely to have Ann Arbor Stage III or IV disease (P = 0.005), bulky disease (P = 0.01), elevated baseline LDH (P = 0.002), elevated baseline CRP (P = 0.017) and higher R‐IPI scores (P = 0.03).The OS at 5 years was 38% in patients with elevated baseline CRP and 74% in patients with low CRP (P &lt; 0.001), while the 5‐year OS was 24% in patients with VTE and 59% in patients without VTE (P &lt; 0.001). On multivariate analysis the baseline CRP (HR: 2.48 [95% CI: 1.65–3.73]; P &lt; 0.001) and presence of VTE (HR: 2.17 [95% CI: 1.42–3.32]; P = 0.002) both retained prognostic significance for OS when controlling for the R‐IPI. Even though the prognostic impact of CRP and thrombosis was valid for the entire cohort, their significance was even more striking when present in the subgroup of patients with poor risk R‐IPI score, where the presence of both VTE and an elevated baseline CRP was associated with a median OS of only 3.3 months (P = 0.001).Summary/Conclusion:This study shows that baseline CRP and the presence of VTE are both independent predictors of worse OS in DLBCL. The combination of poor risk R‐IPI with elevated baseline CRP and venous thrombosis identifies a group of patients with particularly poor outcomes.image

PF312 RESPONSES TO R-CHOP CHEMOTHERAPY INCORPORATING BIOSIMILAR RITUXIMAB (TRUXIMA®) FOR THE FIRST LINE TREATMENT OF DIFFUSE LARGE B-CELL LYMPHOMA – INITIAL EXPERIENCE AT UNIVERSITY COLLEGE LONDON HOSPITAL

Background: In April 2017 the first biosimilar rituximab (Truxima®; NAPP) was approved in the UK for all indications of the reference biologic (MabThera®; Roche). The adoption of biosimilars is expected to deliver significant cost savings in the treatment of many conditions. The approval of Truxima® was based on comprehensive analytical and pre-clinical testing together with confirmatory clinical trials in advanced follicular lymphoma and rheumatoid arthritis with subsequent extrapolation to all licensed indications of MabThera®. There is an absence of clinical trial data supporting the use of biosimilar rituximab in other haematological malignancies, including diffuse large B-cell lymphoma (DLBCL) where the standard of care is R-CHOP chemo-immunotherapy. In the clinical trial leading to the approval of MabThera® for this indication the complete response rate at the end of treatment was 76% in patients who received R-CHOP compared to 62% in the group who received CHOP alone1. Aims: To assess the response to treatment for all patients treated for de novo stage II-IV DLBCL with R-CHOP chemo-immunotherapy including biosimilar rituximab (Truxima®). Methods: All patients starting treatment with R-CHOP for de novo stage II-IV DLBCL were identified from the electronic chemotherapy prescribing system and the following data collected: baseline demographics, performance status, staging, Revised International Prognostic Index (R-IPI), brand of rituximab received, number of R-CHOP cycles received, number of rituximab doses received, CNS prophylaxis received and response to therapy as assessed by end of treatment PET scan. Results: A total of 70 patients have completed treatment with R-CHOP chemo-immunotherapy incorporating biosimilar rituximab (Truxima®). Patients received a median of 6 cycles of CHOP (range: 1–6) and 6 doses of rituximab (range: 2–8). 58 patients completed treatment exclusively with Truxima®. 12 patients switched from MabThera® to Truxima® during their treatment after a median of 3 doses (range: 1–6). Response rates for the whole cohort of patients were as follows: Complete Response (CR): 51/70 (73%), Partial Response (PR): 11/70 (16%), Progressive Disease (PD): 6/70 (9%). Two patients died before response could be assessed. 4/70 (6%) patients switched from R-CHOP to R-GCVP chemo-immunotherapy after a median of 2 cycles (range: 1–5); all four patients achieved a CR.Summary/Conclusion: In our single-centre experience the use of biosimilar rituximab (Truxima®) does not appear to adversely impact the response rate to R-CHOP chemo-immunotherapy in patients with stage II-IV diffuse large B-cell lymphoma as assessed by post-treatment PET scan. Longer term follow-up in a larger patient group is required to confirm these results.

Survival disparities of diffuse large B-cell lymphoma in a community-based cancer center.

7541 Background: Non-Hodgkin’s Lymphoma (NHL) is a heterogeneous group of hematologic malignancy from immature or mature lymphocytes or natural killer cells. It is the 9th leading cause of death for both sexes. Diffuse Large B Cell Lymphoma (DLBCL), a subset of NHL, comprises 30 – 40% of all NHL. The etiology for the racial disparities in survival among patients with DLBCL is still unknown. The Revised International Prognostic Index (R-IPI), a tool which predicts the outcome of DLBCL patients, has not yet been fully validated in African Americans (AA). Methods: We conducted a single cohort study of patients diagnosed with DLBCL from January 1, 2007 to December 31, 2017 from our tumor registry in a single community-based cancer center. We abstracted demographic, clinical, histopathologic, treatment, and R-IPI variables. Our primary endpoint was overall survival (OS). Our secondary endpoints were factors that determine mortality through Cox multivariate analysis. Results: Among 381 patients with NHL, 181 (47.5%) patients had biopsy-proven DLBCL. Median age was 65 years old, 47% were males, 41% were AA, 44% were Caucasians, 46% were stage IV by Ann-Arbor staging. African-Americans (AA) had a median OS of 15.7 months (95% CI, 10.31 to 23.90) compared to non-AA 93.6 months (95% CI, 61.48 to 142.57). Even after adjusting for race, R-IPI was correlated with mortality on all patients. Lactate dehydrogenase levels were significantly higher in AA (P&lt;0.001) but there was no difference in the interval from diagnosis to initiation of treatment in all groups. The presence of B symptoms HR 1.80 (95% CI, 1.17 to 2.77), African-American race HR 2.19 (95% CI, 1.38 to 3.52), positive HIV HR 2.16 (95% CI, 1.15 to 4.05), chronic liver disease HR 1.87 (95% CI, 1.09 to 3.23), and malnutrition HR 2.46 (95% CI, 1.30 to 4.65) were all independently associated with increased mortality. Histopathologic features such as the cell of origin, BCL6, and BCL2 rearrangements were not independently associated with increased mortality. Conclusions: There is an overwhelming disparity in survival among AA with DLBCL. The R-IPI is a reliable tool for predicting mortality in AA with DLBCL.

Comparison of clinical scoring systems in aggressive B-cell lymphomas (BCL): An individual patient-level analysis across international trials (SEAL).

7544 Background: Great heterogeneity in survival exists for patients (pts) newly diagnosed with aggressive BCL. Three scoring systems based on simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the international prognostic index (IPI), revised-IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We studied BCL pts treated with R-CHOP to determine which scoring systems best identifies subgroups with poor outcomes that might benefit from new approaches. Methods: Individual pt data from 7 multicenter trials (1998-2009) of pts with BCL (86% DLBCL) treated front-line with R-CHOP (or variant) were analyzed to determine whether IPI, R-IPI, or NCCN-IPI best discriminated overall survival (OS). The concordance index (c-index) from a proportional hazards model, stratifying on trial and induction therapy, quantified predictive accuracy of each scoring system. Results: 2561 pts (median age 63 yrs, 56% male) were classified into IPI, R-IPI, and NCCN-IPI risk groups (Table). With a median follow-up of 5 yrs, NCCN-IPI had the greatest absolute difference in OS estimates between the highest and lowest risk groups at 1, 3, and 5 yrs, and best discriminated OS (c-index = 0.631, Table). Conclusions: In an independent and large cohort of pts, NCCN-IPI performs best in risk-stratifying pts with aggressive BCL, readily distinguishing pts at high and low risk for treatment failure using clinical parameters (5-yr OS between 48 and 92%). Improvement over the simpler IPI appears incremental, and IPI may remain a valuable alternative. Work integrating molecular features of the tumor into the (NCCN-) IPI is in progress to define high risk groups where targeted novel approaches are needed most. [Table: see text]

Impact of absolute lymphocyte count on prognosis of aggressive non-Hodgkin lymphoma.

e19034 Background: Multiple studies have attempted to identify parameters to predict prognosis and overall survival (OS) in Non-Hodgkin Lymphoma (NHL). Revised International Prognostic Index (R-IPI) is commonly used but does not capture all predictive risk factors in the Rituximab era. Low absolute lymphocyte count (ALC) on follow up after first line therapy has been reported to predict relapse. The prognostic value and exact cut off for low ALC at diagnosis is not known. We aimed to investigate whether ALC at time of diagnosis is an independent predictor for OS in aggressive NHL. Methods: We retrospectively evaluated patients with aggressive NHL treated at our center from 1/2000 to 12/2016 with at least 2 year longitudinal follow up after diagnosis. We retrieved data for baseline characteristics including age, sex, Ann Arbor stage, R-IPI score, HIV status, histopathological diagnosis (Diffuse Large B Cell Lymphoma (DLBCL), Burkitt′s lymphoma, Follicular Lymphoma Grade IIIB, high-grade B cell lymphoma), type of chemotherapy and clinical response. Patients were divided into four subgroups based on ALC at diagnosis: &lt; 500, 501-1000, 1001-1500 and &gt; 1500X109/L. Statistical analysis was done using REDCAP and Stata v13. Results: A total of 92 patients were identified. The average age at diagnosis was 53.4 years, 63% were male and 73.5% were diagnosed with DLBCL. Per R-IPI score, 16.3% were high risk, 31.3% were high intermediate risk, 22.5% low intermediate risk and 30% were low risk. The median OS for patients with ALC &lt; 500 x109/L (5.4%) was 1.5 years, ALC 501-1000 (38%) was 2.3 years, ALC 1001-1500 (23.9%) was 4.25 years and ALC &gt; 1500 (32.6%) was 5.2 years. On multivariate analysis this difference was not statistically significant due to small sample size. Conclusions: We found that low ALC at diagnosis trended towards worse OS in aggressive NHL but did not reach statistical significance on multivariate analysis. Our study is limited by retrospective nature and sample size. Multicenter studies need to be done to validate these results. Studies are also needed to know the exact cut off for low ALC. [Table: see text]

Prognostic Nomogram for Overall Survival in Patients with Diffuse Large B-Cell Lymphoma.

This study aimed to develop a prognostic nomogram in diffuse large B-cell lymphoma (DLBCL) and compare it with traditional prognostic systems. We included 1,070 consecutive and nonselected patients with DLBCL in the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, between 2006 and 2012. A nomogram based on the Cox proportional hazards model was developed. The entire group were divided into the primary (n = 748) and validation (n = 322) cohorts. The 5-year overall survival (OS) rate was 64.1% for the entire group. Based on a multivariate analysis of the primary cohort, seven independent prognostic factors including age, Ann Arbor stage, Eastern Cooperative Oncology Group performance status score, lactate dehydrogenase, β2-microglobulin, CD5 expression, and Ki-67 index were identified and entered the nomogram. The calibration curve showed the optimal agreement between nomogram prediction and actual observation. In addition, the concordance index (C-index) of the nomogram for OS prediction was 0.77 (95% confidence interval [CI], 0.73-0.81) in the primary cohort and 0.76 (95% CI, 0.70-0.81) in the validation, superior to that of the international prognostic index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI (range, 0.69-0.74, p<.0001). Moreover, in patients receiving rituximab plus CHOP (R-CHOP) or R-CHOP-like regimens, compared with IPI (C-index, 0.73; 95% CI, 0.69-0.77), R-IPI (C-index, 0.70; 95% CI, 0.66-0.74), or NCCN-IPI (C-index, 0.71; 95% CI, 0.66-0.75), the DLBCL-specific nomogram showed a better discrimination capability (p < .0001). The proposed nomogram provided an accurate estimate of survival of patients with DLBCL, especially for those receiving R-CHOP or R-CHOP-like regimens, allowing clinicians to optimized treatment plan based on individualized risk prediction. A diffuse large B-cell lymphoma (DLBCL)-specific prognostic nomogram was developed based on Chinese patients with DLBCL. As a tertiary hospital, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences is the number 1 ranked cancer center in China, with more than 800,000 outpatients in 2018. Patients included in this study were nonselected and came from 29 different provinces, municipalities, and autonomous regions in China. Thus, the data is believed to be representative to an extent.

Complications and outcomes in diffuse large B-cell lymphoma with gastric lesions treated with R-CHOP.

Standard therapy for gastric diffuse large B‐cell lymphoma (DLBCL) is considered to be chemotherapy with or without involved‐field radiation therapy. Although R‐CHOP therapy alone is widely used for DLBCL with gastric lesions (DLBCL‐GL), the outcome and incidence of treatment‐related gastric complications following R‐CHOP are not well known. This study aimed to evaluate the outcome after R‐CHOP therapy in patients with gastric DLBCL including gastric complications and to identify risk factors for the complications. Consecutive patients with newly diagnosed DLBCL‐GL treated with R‐CHOP between 2003 and 2014 were retrospectively evaluated. DLBCL‐GL was defined only when pathologically confirmed in the stomach. Of the 96 patients with DLBCL‐GL, 63 patients were diagnosed with gastric symptoms. Eighty‐eight patients (92%) completed six to eight cycles of R‐CHOP. The complete remission (CR) rate was 86%, and 3‐year and 5‐year overall survival rates were 80% and 73%, respectively. Patients were well stratified according to the Revised International Prognostic Index (R‐IPI). Complication rate was 8% (8/96); seven patients had bleeding and three had stenosis. No patients had gastric perforation. Bleeding occurred during the first cycle of R‐CHOP in five patients (5/7, 71%). Patients with gastric complications had a lower R‐CHOP completion rate (50%, P = 0.001) and a lower CR rate (25%, P < 0.001) than those without complications. A low serum albumin level at diagnosis was the only risk factor identified for gastric complications (P = 0.001) and six of the eight patients with complications were shown to be at stage IV. Further studies of DLBCL‐GL are warranted to identify patients at high risk for gastric complications and to provide better treatment strategies.

Prognostic study of 229 follicular lymphoma patients treated with rituximab combined with chemotherapy

目的探究滤泡性淋巴瘤（FL）的临床特征，以及FL国际预后指数（FLIPI）、FLIPI2、IPI、修正IPI（R-IPI）、NCCN-IPI在中国FL患者的预后意义。方法对2008年11月至2018年4月期间以利妥昔单抗联合CHOP（环磷酰胺、多柔比星、长春新碱及泼尼松）方案治疗的229例初治FL患者资料进行回顾性分析，并对所有患者进行各项预后指数评分。对201例完成化疗且有完整随访记录的患者进行单因素及多因素生存分析。结果229例患者中男126例，女103例，中位年龄53（21~82）岁。①对上述预后评分系统中所含的危险因素在患者总生存（OS）和无进展生存（PFS）中的影响进行分析，单因素分析结果显示：年龄>60岁、HGB<120 g/L、血β2微球蛋白升高、骨髓浸润及C反应蛋白（CRP）升高是影响患者OS和PFS的不良因素（P值均<0.05），利妥昔单抗维持组（RM）与非维持组（non-RM）患者的5年OS率分别为93.33%、87.10%（P=0.020），5年PFS率分别为90.81%、63.47%（P=0.003），前者均优于后者；多因素分析结果显示：HGB<120 g/L（P=0.001）、骨髓浸润（P=0.050）、CRP升高（P=0.010）和non-RM（P=0.010）是影响OS的不良预后因素，HGB<120 g/L（P=0.003）、CRP升高（P=0.009）和non-RM（P=0.003）是影响PFS的不良预后因素。②对FLIPI和FLIP2评分预后模型进行比较分析，结果显示：FLIPI预后模型中，低危、中危和高危组患者的5年OS率（P=0.230）和5年PFS率（P=0.160）差异均无统计学意义。FLIP2预后模型中，5年OS率和5年PFS率差异均有统计学意义（P值均<0.001），在利妥昔单抗治疗组中进行分析，低危、中危和高危组患者的5年OS率分别为96.77%、88.89%、80.00%，差异有统计学意义（P=0.042）。结论利妥昔单抗时代FLIPI2可以更好地用于FL危险分层。

A Comparison of Prognostic Indices in Diffuse Large B-Cell Lymphoma within the UK NCRI R-CHOP 14 Versus 21 Phase III Trial

A Comparison of Prognostic Indices in Diffuse Large B-Cell Lymphoma within the UK NCRI R-CHOP 14 Versus 21 Phase III Trial

Impact of Creatinine Clearance in Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP : A Real-World Long-Term Observation Analysis at a Single Institute

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. DisclosuresNishimura: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.

A Global, Randomized, Placebo-Controlled, Phase 3 Study of Ibrutinib Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (RCHOP) in Patients with Previously Untreated Non-Germinal Center B-Cell-like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL)

A Global, Randomized, Placebo-Controlled, Phase 3 Study of Ibrutinib Plus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (RCHOP) in Patients with Previously Untreated Non-Germinal Center B-Cell-like (GCB) Diffuse Large B-Cell Lymphoma (DLBCL)

Quality Initiative in Clinical Practice: A Single Institution Appraisal of Quality Metrics in the Management of Newly Diagnosed Diffuse Large B-Cell Lymphoma Based on the American Society of Hematology Practice Improvement Module

▪ABSTRACTBackground: In 2014, the American Society of Hematology (ASH) established a practice improvement module (PIM) incorporating quality metrics for management of diffuse large B cell lymphoma (DLBCL). Such PIMs have allowed physicians to monitor the quality of care in their practice. We implemented a DLBCL quality improvement initiative (QII) at our institution in January, 2015. In an appraisal of this initiative, we reviewed the ASH PIM metrics and included several others to assess adherence to guidelines for treatment of DLBCL and to examine the need for institutional improvement.Methods: Patients who were newly diagnosed with DLBCL and received treatment at our institution from January 2006 through December 2017 were identified. Electronic medical records were reviewed for documentation of ASH PIM quality measures (e.g., key pathologic features of DLBCL, lymphoma staging, screening for hepatitis B virus (HBV) infection in patients receiving rituximab-based chemotherapy, etc). We also reviewed the proportion of patients who had assessment of prognosis by revised International Prognostic Index (r-IPI) score, testing for hepatitis C (HCV), HIV viral infections, chemotherapy education, and the addition of rituximab in the treatment regimen of CD20+ DLBCL.Results: Following implementation of the QII, our institution saw improvement in most quality metrics. Particularly significant were improvements in reporting of key molecular features (45.45% to 91.6%, P < 0.0001), screening for HBV (41.82% to 91.67%, P < 0.001) and HIV infections (33.94% to 87.5%, P < 0.0001). All patients post-QII had a PET-CT scan for staging of DLBCL and there was a significantly lower use of bone marrow biopsy (61.2% to 33.33%, P = 0.011).Conclusion: Implementation of a quality initiative and employing standardized metrics can aid in improving institutional quality of care for patients with newly diagnosed DLBCL, and allows opportunity to build and ensure better adherence to evolving national and professional patient care guidelines. DisclosuresNo relevant conflicts of interest to declare.

Impact of MYD88L265P mutation Status on Histological Transformation of Waldenstrom Macroglobulinemia

Impact of MYD88L265P mutation Status on Histological Transformation of Waldenstrom Macroglobulinemia

Available prognostic models for risk stratification of diffuse large B cell lymphoma patients: a systematic review.

The International Prognostic Index (IPI) has been used for risk stratification for a long time in diffuse large B cell lymphoma (DLBCL). Based on new clinical and biological prognostic markers, many new prognostic models have been described. This review aims to present the progress in development and validation of these prognostic models. A comprehensive literature review was performed to identify studies that proposed a new prognostic model in DLBCL. A total of 38 studies met the inclusion criteria. The IPI, revised IPI (R-IPI), and National Comprehensive Cancer Network (NCCN)-IPI were the most studied prognostic indexes, externally validated and commonly used to compare to other models. Despite an increasing number of prognostic models have been proposed lately, most of them lack external validation. Further studies, that combine biological and clinical markers with prognostic significance, are needed to determine the optimal prognostic tool for more personalized treatment approach to DLBCL patients.