Standard International Prognostic Index Research Articles

Prognostic Effect Of More Than 1 Extranodal Site Of Disease For Patients With Diffuse Large B Cell Lymphoma (DLBCL) In The Rituximab Era: Results From The UK NCRI R-CHOP 14 Versus 21 Trial

Background The international prognostic index (IPI) was first described in 1993 by Shipp et al and is the most commonly used prognostication tool in DLBCL. The IPI combines 5 poor prognostic parameters (age >60 years, elevated LDH, performance status ≥2, stage III/IV and >1 site of extranodal disease). Use of the age-adjusted IPI (AA-IPI) is recommended for patients 1 extranodal site of disease was no longer prognostic. In this analysis, we explored the prognostic implications of individual IPI parameters including >1 site of extranodal disease in the context of a large randomized phase III study. Methods The R-CHOP 14 versus 21 phase 3 open-label randomised controlled trial has been previously reported [Cunningham et al, The Lancet, Volume 381, Issue 9880, p1817-1826]. 1080 patients were randomly assigned to receive six cycles of R-CHOP every 14 days plus 2 cycles of rituximab (R-CHOP-14) or eight cycles of R-CHOP every 21 days (R-CHOP-21). A multivariate analysis of prognostic factors was also undertaken, including age (continuous variable), gender, stage (I-IV), performance status (PS; 0 vs 1 vs 2), lactate dehydrogenase (LDH) concentration (normal vs elevated), presence or absence of B symptoms and number of extranodal sites ( 1). We particularly wished to assess whether >1 site of extranodal disease is an independent prognostic factor in our dataset, both in all treated patients (n=1071) and in those<60 years (n=473). A comparison of overall survival (OS) between the standard IPI and AA-IPI groupings was performed in patients<60 years using the Kaplan Meier (KM) method. Results In multivariate analysis increased age, stage, and PS, as well as raised LDH and presence of B symptoms were associated with poor OS. Whilst >1 site of extranodal disease was not found to be independently prognostic, it was associated with a non-significant trend towards poorer OS (HR 1.312, p=0.057). When the analysis was restricted to patients 1 extranodal site of disease was found to be associated with a significantly worse OS (HR 2.19, p=0.0025). This is in contrast to the original age-adjusted IPI which did not find >1 extranodal site to be a relevant prognostic factor in the<60 years group. [Table 1][1] displays the effects of >1 extranodal site on OS and PFS. OS in patients<60 years according to standard IPI and AA-IPI are shown in [figures 1][2] and [2][3]. Using the AA-IPI (which excludes weighting for number of extranodal sites) the poorest prognostic group have a 2 yr OS of 55%. Using the standard IPI in the same population there appears to be better differentiation of prognostic groups with the poorest prognostic group having a 2 yr OS of 40%. View this table: Table 1 Prognostic significance of >1 extranodal site of disease in multivariate analysis (OS and PFS) ![Figure 1:][4] Figure 1: IPI score and overall survival in patients<60 years (n=476) ![Figure 2:][4] Figure 2: Age-adjusted IPI score and overall survival in patients<60years (n=476) Conclusion In our cohort of over 1000 patients from a randomized prospective phase III trial >1 extranodal site of disease was found to be associated with a significantly worse OS in patients<60 years with DLBCL. The use of the standard IPI was superior to the age-adjusted IPI in prognostication for patients<60 years in our dataset. Extranodal disease should be identified as a priority at baseline using modalities such as PET, to assign patients to the correct prognostic group. Accurate identification of poor risk patients will help to improve our understanding of their disease biology and guide future therapeutic strategies. Disclosures: Cunningham: Novartis: Research Funding; Astra-Zeneca: Research Funding; Merck KGA: Research Funding; Celgene: Research Funding; Sanofi-Aventis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Merck: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Hawkes: Roche: Travel expenses Other. Jack: Roche: Research Funding; Genentech: Research Funding. Pocock: Roche: Membership on an entity’s Board of Directors or advisory committees, Travel expenses Other; Pfizer: Membership on an entity’s Board of Directors or advisory committees. Ardeshna: Roche: Honoraria, Research Funding. Radford: Roche: Consultancy; Bayer-Schering: Consultancy; Millenium Pharmaceuticals: Consultancy, Research Funding; Napp Pharmaceuticals: Consultancy; Novartis: Consultancy; GlaxoSmithKline: Consultancy. McMillan: Roche: Consultancy, Honoraria, Research Funding, Travel expenses Other. Davies: Roche: Consultancy, Travel expenses Other. Turner: Roche: Travel expenses Other. Johnson: Roche: Membership on an entity’s Board of Directors or advisory committees, Travel expenses Other. Linch: Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Chugai Pharma: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity’s Board of Directors or advisory committees; Hospira: Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria. [1]: #T1 [2]: #F1 [3]: #F2 [4]: pending:yes

Cancer Antigen 125 Serum Level in Head and Neck Diffuse Large B-Cell Lymphoma

Background : Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of the Non-Hodgkin Lymphoma (LNH). Until now, lactate dehydrogenase (LDH) is the only tumor marker to assess DLBCL progression; however, increased LDH is a relatively non-specific biomarker. Cancer antigen 125 (CA-125) serum level have been used as a tumor marker in ovarian cancer. The aim of this study was to explore the possible role of CA-125 serum level as a tumor marker in head and neck DLBCL. Methods : This was an observational descriptive study among consecutively sampled DLBCL patients. CA-125 serum level examination was carried out (ADVIA Centaur CA-125II) and described along with the clinical characteristics of DLBCL patients. Results : DLBCL was mostly observed in males (54.05%), most often in the 55-65 year age group (51.3%), with stage 1 DLBCL was the most prevalent (71.9%). The mean CA-125 serum level was 22.9 U/ml and increased in patients with advanced DLBCL. Conclusions : Increased CA-125 serum level in DLBCL, especially at advanced stages, suggests that CA-125 serum level may be of benefit as a tumor marker in the head and neck DLBCL. Further study is in need to explore the role of CA-125. 1. Kementerian Kesehatan Republik Indonesia. Data dan kondisi penyakit limfoma di Indonesia. InfoDatin Pusat Data dan Informasi Kementerian Kesehatan RI. 2015 [cited 2020 March 18] Available from: https://www.kemkes.go.id/resources/download/pusdatin/infodatin/infodatin-limfoma.pdf 2. Dwianingsih EK, Indrawati, Hardianti MS, Malueka RG , Iswar RR, Sutapa S, et al. Histopathological features of lymphoma in Yogyakarta, Indonesia. Asian Pac J Cancer Prev. 2016;17(9):4213–16. 3. Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI. Riset Kesehatan Dasar (RISKESDAS) 2013. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI; 2013 4. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27):3059–67. 5. Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(14):2373-2380. 6. Gutiérrez A, Martínez-Serra J, Barceló B, Sampol A, Vinas L, Gonzales G, et al. Prognostic value of serum CA125 levels in diffuse large B-cell lymphoma: potential role of a new sex and age adjusted reference value. Int J Lab Hematol. 2010; 32(6 Pt 2): 582–9. 7. Dilek I, Ayakta H, Demir C, Meral C, Ozturk M. CA 125 levels in patients with Non-Hodgkin lymphoma and other hematologic malignancies. Clin Lab Haematol. 2005;27(1):51–5. 8. Memar B, Aledavood A, Shahidsales S, Ahadi M, Farzadnia, Raziee HR, et al. The prognostic role of tumor marker CA-125 in B-Cell non-Hodgkin’s Lymphoma. Iran J Cancer Prev. 2015;8(1):42–6. 9. Garg S, Goyal B. Evaluation of CA-125 as a prognostic marker in patients with Non-Hodgkin’s lymphoma. International Journal of Medical and Health Research. 2017;3(4):13–5. 10. Paoli CJ, Bach BA, Quach D, Tsai KT, Wong B, Kallich J. Performance status of real-world oncology patients before and after first course of chemotherapy. The Journal of Community and Supportive Oncology. 2014; 12(5):163–70. 11. Yadav C, Ahmad A, D’Souza B, Agarwal A, Nandini M, Prabhu KA, et al. Serum lactate dehydrogenase in Non-Hodgkin’s lymphoma: a prognostic indicator. Indian J Clin Biochem. 2016;31(2):240–2.

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

CNS Relapse Risk in Consecutive R-CHOP/R-Mini-CHOP-Treated Elderly DLBCL Is Low, with High Risk Particularly Apparent in Those with CNS IPI 5-6 and/or Renal/Adrenal Involvement

CNS Relapse Risk in Consecutive R-CHOP/R-Mini-CHOP-Treated Elderly DLBCL Is Low, with High Risk Particularly Apparent in Those with CNS IPI 5-6 and/or Renal/Adrenal Involvement

Interim 18F-FDG PET/CT improves the prognostic value of S-IPI, R-IPI and NCCN-IPI in patients with diffuse large B-cell lymphoma.

The current study aimed to explore whether the efficiency of the standard International Prognostic Index (S-IPI), revised-IPI (R-IPI) and enhanced-IPI (NCCN-IPI) in evaluating the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) may be improved by interim 18F-FDG PET/CT. A total of 185 patients with newly diagnosed DLBCL were enrolled in the current study. All patients underwent interim PET/CT following the 4th cycle of chemotherapy. Patients were divided into different risk groups using S-IPI, R-IPI and NCCN-IPI and further subdivided into risk groups using interim PET/CT. Interpretations were evaluated for 2-year progression-free survival (PFS) and overall survival (OS). With a median follow-up time of 44 months, the 2-year PFS and OS were 60% [95% confidence interval (CI) 53–67%] and 81% (95% CI 74–86%), respectively. Analysis of S-IPI and NCCN-IPI identified no significant difference in PFS and OS between high intermediate and high risk groups. However, there were significant differences in the PFS and OS between the low and low intermediate risk groups (P<0.01). Interim PET/CT was used to redistribute patients in the higher risk group into PET negative and positive groups (P<0.01) and arallel results were observed in the lower risk group. In R-IPI, interim PET/CT identified a significant difference between PFS and OS in the good and poor risk groups but not in the very good risk group. Therefore, the results of the current study indicate that S-IPI, R-IPI and NCCN-IPI are three clinically useful prognostic indexes for patients with DLBCL. Interim PET/CT may improve the prognostic value of S-IPI, R-IPI and NCCN-IPI in predicting 2-year PFS and OS, particularly in patients with a high IPI score.

Clinical Usefulness of Inflammatory Factors Based Modified International Prognostic Index in Diffuse Large B Cell Lymphoma Treated with Rituximab Combined Chemotherapy

Background : Prognosis of diffuse large B cell lymphoma (DLBCL) is very varied from cure to death. So the prediction for prognosis of DLBCL is very important to make a decision regarding the treatment. Now, international prognostic index (IPI) risk model is widely known as the powerful prognostic indicator for lymphoma. However, many inflammatory factors have been demonstrated as prognostic factors in patients with DLBCL such as C-reactive protein (CRP), ferritin, ¥â2-microglobulin (B2MG), absolute lymphocyte count (ALC) and albumin etc. But LDH is the only inflammatory factor in those of IPI. So we find a new prognostic risk model (inflammatory factors based modified IPI risk model ; inflammatory-IPI) including other inflammatory prognostic factors for predicting more correct survival outcomes and progression free survival (PFS) in patients with DLBCL treated with rituximab combined cyclophosphamide, adriamycin, vincristine and prednisone (RCHOP).Methods: A total of 278 patients who were newly diagnosed with DLBCL and received RCHOP at hospitals throughout South Korea between January 2007 and December 2014 were enrolled retrospectively in the current study. Baseline serum CRP, ferritin, B2MG, ALC, albumin and factors of IPI were measured within 4 weeks before beginning the first line of chemotherapy. Each inflammatory factor of serum CRP > 1.5mg/dL, ferritin > 500ng/mL, B2MG > 3.5mg/L, ALC level < 1.0x109/L, serum albumin < 3.5g/dL, LDH level > 450 IU/L was defined as an abnormal findings, and if the sum of these abnormal findings are not fewer than 2, it is given 1 point as a factor of inflammatory-IPI instead of LDH. After that, sum of this point and the number of negative prognostic factors present at the time of diagnosis (age > 60 years, ECOG performance status ¡Ã 2, extranodal site ¡Ã 2, stage III/IV disease) is named the inflammatory-IPI. The inflammatory-IPI risk model were divided into four groups seems like IPI according to the scores ; low risk were 0 or 1 score, low-intermediate risk were 2 scores, and high-intermediate risk were 3 scores, high risk were 4 scores respectively.Results: In univariate analysis, the following factors showed significant higher 5 years overall survival rates (OS) : age (p=0.001), stage III/IV disease (p=0.008), LDH level (p<0.001), CRP (p=0.001), ferritin (p<0.001), B2MG (p<0.001), revised IPI (p<0.001). These factors also showed significant higher 5 years PFS. But some other factors did not showed significant OS and PFS in our data : ECOG, extranodal involvement, ALC, albumin. The studied groups were comprised of 117 patients in low risk group, 63 patients in low-intermediate group, 56 patients in high-intermediate group, 40 patients in high risk group according to inflammatory-IPI scores including sum of abnormal inflammatory findings. The OS and PFS according to the inflammatory-IPI showed significant differences (p<0.001 and p<0.001, respectively) (Figure 1).Conclusions: The survival outcomes showed significant differences between risk groups which were categorized by inflammatory-IPI. This new inflammatory-IPI risk model could be supplemented the deficiency of standard IPI by including other prognostic inflammatory factors as well as LDH. It will be helpful to predict prognosis and make treatment planning in patients with DLBCL treated with RCHOP. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Results of an Ongoing Phase 2 Study of Brentuximab Vedotin with Rchp As Frontline Therapy in Patients with High-Intermediate/High-Risk Diffuse Large B Cell Lymphoma (DLBCL)

Results of an Ongoing Phase 2 Study of Brentuximab Vedotin with Rchp As Frontline Therapy in Patients with High-Intermediate/High-Risk Diffuse Large B Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma: A single-institution experience of patient outcomes.

271 Background: The Windsor Regional Cancer Program (WRCP) was determined to have consistently been a top performer in time to treatment of diffuse large B cell lymphoma in this Canadian province (http://www.csqi.on.ca/by_type_of_cancer/lymphoma/lymphoma_treatment/). We endeavored to determine whether faster time to diagnosis and treatment for diffuse large B-cell lymphoma (DLBCL) influenced the IPI score (International Prognostic Score), thereby predicting an improved clinical outcome in these presenting patients. Methods: The WRCP services a catchment area of 650,000 people. A retrospective chart review was conducted for patients diagnosed with DLBCL at the Windsor Regional Cancer Program (WRCP) between 2006-2012. Information collected included the five factors for scoring by the International Prognostic Index (IPI) – age, performance status, LDH, stage, and number of extranodal sites – chemotherapy regimen, relapses, existence of second malignancies, cause of death, and dates of diagnosis, last follow-up, and death. We analyzed the relationship between prognostic factors and these clinical outcomes, and also compared the IPI scores for this cohort of patients against a similar population in another Canadian province, British Columbia. Results: It is established that compared to other cancer centres in Ontario, the WRCP is consistently reporting a shorter diagnosis to treatment metric when compared to their counterparts in Ontario, Canada. When compared to historical Canadian data, presenting IPI scores for DLBCL patients were lower on average for patients treated at the WRCP than those reported in British Columbia, Canada by Sehn et al. [Sehn, L. H., et al. (2007). The revised International Prognostic Index is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood, 109(5), 1857-1861.]. Conclusions: A lower presenting IPI score is known to be correlated improved lymphoma related outcome. With attention to the metric of diagnosis to treatment &lt; 30 days for diffuse large B cell lymphoma, we expect an improved lymphoma related outcome for our patients. We recommend ongoing attention to this metric, in order to improve outcomes for our patients.

Risk Stratification Combining MYC Immunohistochemistry with Standard IPI Has Utility in Patients with Diffuse Large B-Cell Lymphoma

BackgroundThough the majority of patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL) are curable with R-CHOP chemotherapy, a significant proportion will relapse or have refractory disease. The most commonly used clinical tool is the international prognostic index (IPI), though this cannot fully capture the heterogeneity of cases seen in practice. In recent years biomarkers such as MYC are entering clinical use. Pts with lymphomas demonstrating dual abnormalities of MYC in association with BCL2 and/or BCL6-known as 'double-hit' lymphomas are consistently shown to have poorer disease free and overall survival. While Fluorescence in-situ hybridization (FISH) for MYC translocation is the gold-standard, immunohistochemistry (IHC) is faster and significantly cheaper. Studies in recent years have confirmed the prognostic significance of increased MYC expression by IHC. Due to significant inter-laboratory variability however, internal validation is required.MethodsTissue samples of pts treated at Royal North Shore Hospital in Sydney, Australia between 2003-2012 were retrospectively assessed. Pts were included if they were transplant eligible (age <70 years), and had been treated for de novo DLBCL with a rituximab containing regimen. Samples were scored for MYC IHC as well as BCL2 and BCL6. Clinical data including IPI score, treatment and outcomes were also collected. Treatments were stratified into standard R-CHOP-like versus more intensive regimens including R-Hyper-CVAD and dose-adjusted R-EPOCH.A significant cut-off for MYC staining was determined using X-Tile (Rimmlab, New Haven, CT) and confirmed with the log-rank test. Estimation of OS and EFS was performed using the Kaplan-Meier method. Pt characteristics were compared using Chi-squared test. Statistical analysis was performed using MedCalc 15.4 (MedCalc software, Ostend, Belgium). Ethics approval was received for a retrospective study.Results105 patients met study criteria. The 5 year OS and EFS was 86% and 77% respectively (Figure 1 and 2). The optimal cut-off for positive MYC IHC was >70%. This was seen in 23% of samples. From the 13 cases with MYC FISH results, the positive and negative predictive values of positive MYC IHC were 50% and 92% respectively. There was no significant difference between the MYC positive and negative groups with respect to demographics or IPI score (Table 1). Significantly more patients with MYC positivity received intensive treatment (37% versus 16%, p=0.047). Despite this, 5 year OS was significantly poorer at 51% versus 87% at median follow-up of 40 months (P=0.0025, Figure 3). There was a trend towards worse EFS at 61% versus 75% though this did not reach statistical significance (P=0.242). On multivariate analysis, MYC IHC and IPI score were the only independent prognostic factors. Based on the relative odds ratio, a combined scoring system was designed, attributing 1 point for positive MYC IHC and/ or IPI intermediate-high risk, and 2 points for IPI high risk. This resulted in 4 risk groups with significantly different 5 year OS of 94%, 78%, 45% and 0% (P<0.0001).DiscussionMYC IHC is of independent prognostic significance. Due to significant variability between laboratories, local validation is required. A composite score combining IPI and MYC IHC is simple to calculate and may provide better prognostic utility than either factor alone. Ongoing prospective studies investigating the role of clinical risk stratification and newer biomarkers are required to identify patients likely to need more intensive or novel therapies. [Display omitted] DisclosuresImlay-Gillespie:Novartis: Honoraria. Arthur:Amgen: Honoraria; Novartis: Honoraria; BMS: Honoraria. Mackinlay:Roche: Research Funding; Sanofi Aventis: Research Funding. Mulligan:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi Aventis: Research Funding.

Outcome of Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Subgroup Analysis from the UK NCRI R-CHOP 14 Vs 21 Trial

Background:Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis compared to younger patients. Dose intense administration of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP14) is superior to 3-weekly CHOP in elderly DLBCL patients (Pfreundschuh, Blood 2004), but this benefit has not been demonstrated with addition of rituximab (Delarue, Lancet Oncol 2013). We have previously shown that R-CHOP14 did not improve outcome compared to standard R-CHOP21 in newly diagnosed DLBCL patients aged 19-88 years across all subgroups (Cunningham, Lancet 2013). Here, we provide a detailed subgroup analysis of elderly patients (over 60 years) from the UK NCRI R-CHOP14 vs 21 randomised phase 3 trial.Methods:Between 2005 and 2008, 1080 patients were randomly assigned to receive 8 cycles R-CHOP21 or 6 cycles R-CHOP14 (+ G-CSF) with two additional rituximab applications. Of these, 604 patients were over 60 years and included in the current analysis (301 in the R-CHOP21 arm, 303 in the R-CHOP14 arm), with a median follow-up of 45 months.Results:Baseline characteristics were well balanced between treatment arms. 36% of patients were over 70 years, 15% had a WHO performance status (PS) of 2, 65% stage III/IV disease, 44% bulky disease and 42% B symptoms. There was a trend towards a higher rate of BCL6 rearrangements (26% vs. 16%; P=0.10) and concurrent MYC - and BCL2 rearrangements (double hit lymphoma as determined by FISH, 8% vs. 2%; P=0.06) in the R-CHOP14 arm compared to the R-CHOP21 arm.85% (257/303) of patients received 8 cycles of R-CHOP14, whereas only 76% (230/301) completed all 8 cycles R-CHOP21. However, percentage of patients receiving at least 6 cycles of therapy was similar (88% and 89%, respectively). Dose delays of myelosuppressive drugs occurred more frequently in patients receiving R-CHOP21 vs. R-CHOP14 (51% vs. 39%; P=0.03) due to a higher incidence of haematological toxicities likely related to the reduced use of G-CSF. G-CSF was mandatory for patients on R-CHOP14 and was given to 57% of patients on R-CHOP21 as secondary prophylaxis. The frequency of dose reductions was similar in the R-CHOP21 and R-CHOP14 arms (15% vs. 16%; P=0.73). Toxicities of grade III+ were seen in 72% and 60% of patients in the R-CHOP14 and R-CHOP21 arms, respectively. There was evidence of a higher incidence of grade III+ neutropenia (62% vs. 36%) and a lower rate of thrombocytopenia (7% vs. 12%) in the R-CHOP21 arm compared to R-CHOP14. The incidence of fever and infections was similar in both arms.There was no evidence of a difference in response rates between the R-CHOP14 and R-CHOP21 arms [complete response (CR)/unconfirmed CR (CRu) rates: 62% vs. 67%, respectively; overall response rate both 91%]. CR/CRu rates after 4 cycles of therapy were 33% and 39% respectively (P=0.15). There was no difference regarding progression-free survival (PFS) and overall survival (OS) between arms, neither in the total cohort of elderly patients, nor in the subgroup of patients over 70 years [OS (all elderly): hazard ratio (HR) 0.91 (95% CI: 0.67-1.24); P=0.55; PFS (all elderly): HR 0.98 (95% CI: 0.74-1.29); P=0.86]. 3-year PFS was 71% (95% CI: 67-74) in all patients over 60 years and 64% (95% CI: 58-71) in patients over 70 years. 3-year OS was 75% (95% CI: 72-79) and 67% (95% CI: 61-74) in patients over 60 years and over 70 years, respectively. In multivariate analysis including individual factors of the International Prognostic Index (IPI), as well as age as continuous variable, gender, presence of B symptoms, bulky disease, b2-microglobulin higher than 3mg/l and albumin higher than 35 g/l, only age was of independent prognostic significance for OS (P=0.01).Besides the standard IPI and the NCCN-IPI, an elderly IPI (E-IPI; Advani, BJH 2010) and the ABE4 score (Prochazka, PLoS One 2014) have been proposed for better prognostication of elderly DLBCL patients. A detailed comparison of these different prognostic models in our dataset will be presented at the meeting.Conclusion:Outcome and toxicities in DLBCL patients over 60 years treated within the NCRI R-CHOP14 vs 21 trial are comparable to results from other randomised studies investigating R-CHOP14 or R-CHOP21 in elderly DLBCL patients. Our data further support the similar efficacy and tolerability of both R-CHOP variants for first-line treatment of this patient group. DisclosuresCunningham:Amgen: Research Funding; Medimmune: Research Funding; Astra Zeneca: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; Merrimack: Research Funding; Merck Serono: Research Funding; Celgene: Research Funding; Sanofi: Research Funding. Pocock:Janssen: Honoraria. Ardeshna:Roche: Honoraria.

MYC and BCL-2 adjusted-International Prognostic Index (A-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP.

The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with diffuse large B-cell lymphoma (DLBCL) for the past 20 years. The utility of the IPI must be reassessed in the era of immunochemotherapy. Seven risk factors at diagnosis were identified, and a maximum of 7 points were assigned to each patient. Four risk groups were created: low (0-1), low-intermediate (2-3), high-intermediate (4), and high (5-7). Using MYC and BCL-2 clinical data from the Drum Tower Hospital collected during the rituximab era, we performed a retrospective analysis of patients with DLBCL treated with R-CHOP and built an biological markers adjusted IPI with the goal of improving risk stratification.Clinical features from 60 adults with de novo DLBCL diagnosed from 2008-2013 were assessed for their prognostic significance. The IPI remains predictive, but it cannot identify the high-risk subgroup. Compared with the IPI, the MYC and BCL-2 adjusted-IPI (A-IPI) better discriminated patients in the high-risk subgroup (4-year overall survival [OS]: 33.3%) than did the IPI (4 year OS: 48.0%). In the era of R-CHOP treatment, MYC and BCL-2 adjusted-IPI is more powerful than the IPI for helping guide treatment planning and interpretation of clinical trials.

Prognostic impact of concordant and discordant bone marrow involvement and cell-of-origin in Korean patients with diffuse large B-cell lymphoma treated with R-CHOP

AimsPrevious studies have suggested many prognostic factors in diffuse large B-cell lymphoma (DLBCL), but the prognostic importance of cell-of-origin and discordant bone marrow involvement remains unclear. The aim of this...

Comparison of prognostic models for patients with diffuse large B-cell lymphoma in the rituximab era

Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1 × 10⁹/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13 %, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies.

Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project.

The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) -cell lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age ≥ 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) ≥ 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age ≥ 60 years, PS ≥ 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS ≥ 2, ENSs > one, B symptoms, and platelet count < 150 × 10(9)/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065). AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies.

Reassessment of the prognostic value of the International Prognostic Index and the revised International Prognostic Index in patients with diffuse large B-cell lymphoma: A multicentre study

The International Prognostic Index (IPI) is a widely accepted model that is used to predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) who are treated using chemotherapy. However, the prognostic value of the IPI has been a focal point of debate in the immunochemotherapy era. The aim of this study was to reassess the value of the IPI and revised IPI (R-IPI) in a Chinese population. A multicentre retrospective analysis of DLBCL patients who were treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy alone or chemotherapy plus rituximab (R-CHOP-like) was performed. The prognostic values of IPI and R-IPI at the time of diagnosis with respect to overall survival (OS) and progression-free survival (PFS) were evaluated. Among the 438 patients in the study, 241 received a CHOP-like regimen and 197 patients received an R-CHOP-like regimen. Although the IPI remained predictive for the CHOP-like group, it failed to distinguish between the various prognostic categories in the R-CHOP-like group. Notably, redistribution of the IPI factors into R-IPI factors identified three discrete prognostic groups with significantly different outcomes in both the CHOP-like and R-CHOP-like groups. In the R-CHOP-like group, these three risk groups, very good, good and poor, had distinctly different 3-year PFS rates of 96, 84.3 and 67.5% (P=0.001), and 3-year OS rates of 96, 87.6 and 71.1% (P=0.003), respectively. Our study demonstrates the power of the R-IPI as a simplified and more clinically relevant predictor of disease outcome than the standard IPI in DLBCL populations in the rituximab era. Therefore, the R-IPI merits further study in a larger population-based prospective study.

Re-Assessment of the Prognostic Value of International Prognostic Index (IPI) and Revised IPI (R-IPI) in Patients with Diffuse Large B-Cell Lymphoma Treated with or without Rituximab in Chinese Populations: A Retrospective Multicenter Study by Shanghai Lymphoma Research Group

Abstract 2649 Background:The International Prognostic Index (IPI) is a widely accepted prognostic factor system for diffuse large B cell lymphoma (DLBCL) patients treated with chemotherapy. However, the prognostic value of IPI has been a focal point of the debate in the era of immuno-chemotherapy. Recently, the study of British Columbia group suggested that a revised IPI (R-IPI) which redistributed the IPI factors into 3 distinct prognostic groups provided a more clinically useful prediction of outcome for patients with DLBCL. In order to reassess the value of IPI and R-IPI in unselected Chinese population, we conducted this study. Methods:A multicenter retrospective analysis of DLBCL patients treated with CHOP-like chemotherapy alone or plus rituximab was performed by Shanghai Lymphoma Research Group. In total, 438 patients of newly diagnosed DLBCL treated at 6 participated hospitals were included during the period of 1997–2008. The prognostic value of IPI and R-IPI at diagnosis with regards to overall survival (OS) and progression-free survival (PFS) was evaluated. Results:The median age at diagnosis was 50 years (range, 18–83 years), and the median follow-up was 34 months (range, 3–145 months). Among them, 241 patients received CHOP-like regimen, whereas 197 had rituximab (R)-CHOP-like regimen. While IPI remained predictive in CHOP-like group, it could not distinguish between each prognostic category in the R-CHOP-like group (Fig.1). Redistribution of the IPI factors into a R-IPI identified three distinct prognostic groups with significantly different outcomes both in the patients treated with and without rituximab. In R-CHOP-like arm, these three risk groups had distinctly different rates of 3-year progression-free survival rates of 96%, 84.3% and 67.5% (P<0.001), respectively, and 3-year overall survival rates of 96%, 87.6% and 71.1% (P<0.001), respectively (Fig.2). [Display omitted] [Display omitted] Conclusions:Our study underscores the power of R-IPI as a simplified and more clinically relevant predictor of the disease outcomes than the standard IPI in Chinese DLBCL populations in the rituximab era, and it deserves a further study in larger population-based prospective study. Disclosures:No relevant conflicts of interest to declare.

Validation of the Elderly IPI (E-IPI) for Patients with Diffuse Large B Cell Lymphoma Using An Independent Data Set From the RICOVER-60 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)

Abstract 1568 Background:The International Prognostic Index (IPI) is a robust clinical prognostic tool in diffuse large B cell lymphoma (DLBCL) and identifies four risk groups with predicted five-year survival rates. We have previously reported that an alternative index, the E-IPI (age cut off 70 years rather than 60 as used in the IPI) provided better discrimination in outcome for patients >60 years with DLBCL treated with RCHOP in the US Intergroup trial E4494 (Advani et al BJH 2010). The aim of this study was to validate our findings in an independent data set. Patients and Methods:We compared the conventional IPI and the E-IPI in the RICOVER-60 data set of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) in which patients with DLBCL >60 years were treated with RCHOP-14. Patient distribution and overall survival (OS) were assessed according to the standard IPI and E-IPI. OS was estimated by the Kaplan-Meier method and compared across prognostic groups of the IPI and E-IPI using the log-rank test. Cox proportional hazards model was used to estimate the hazard ratio (HR) with the low risk group as the reference group. Performance of indices was compared by a measure of global fit (Akaike’s information criteria, AIC), concordance measures CPE (concordance probability estimate) and C-statistic (or AUC). Low values of AIC indicate a better fit, whereas high values of CPE and C-statistics indicate better discrimination. The AUC (area under the receiver operator characteristic curve) over time was calculated for both the IPI and the E-IPI. Results:Six hundred and ten patients treated with R-CHOP-14 had a median observation time of 34.3 months. Patient characteristics were: stage III/IV, 50%; >1 extranodal site, 18%; elevated LDH, 50%; ECOG performance status ≥2, 15%. The median age was 68.5 years with 37% greater than 70 years. On univariate analysis all of these characteristics were significant for 3 year OS. The IPI and E-IPI both distinguished 4 prognostic groups (low, low intermediate, high intermediate and high risk). In E-IPI versus IPI more patients were categorized under the low risk group (47% versus 30%) and fewer as high intermediate (15% versus 25%). Both the IPI and E-IPI provided prognostic discrimination for OS for the 4 groups (Table I). The C-statistic at 2 y for OS are 0.659 (95% CI: 0.596, 0.721) for IPI and 0.679 (95% CI: 0.616, 0.742) for E-IPI. The AUC ranked the E-IPI higher than the IPI over all event times. Similar rankings were obtained using the global model fit criterion (AIC) and discrimination measure (CPE). Conclusion:For patients >60 years treated with R-CHOP in the RICOVER-60 study, both the IPI and E-IPI provided prognostic discrimination for OS; however, the E-IPI outperformed the conventional IPI validating our previous findings. The E-IPI is a useful index to incorporate in studies for risk stratification of patients > 60 years with DLBCL.Table I:Distribution and outcome of patients according to the IPI and E-IPI% OSGroupFactorsPatients %Estimated 3 y OS (95% CI)Estimated HR (95% CI)Wald p-valueIPIL0–13088 (82,92)1-LI22879 (72,85)2.1 (1.2,3.6)0.0064HI32567 (59,75)3.4 (2.1,5.7)<0.0001H4–51658 (47,67)4.6 (2.7,7.8)<0.0001E-IPIL0–14787 (82,90)1-LI22775 (67,81)2.2 (1.4,3.3)0.0004HI31558 (47,68)3.7 (2.3,5.8)<0.0001H4–51051 (38,63)5.0 (3.1,8.0)<0.0001L, Low; LI, Low intermediate; HI, High intermediate; H, High Disclosures:Pfreundschuh:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Evaluation of prognostic values of clinical and histopathologic characteristics in diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy

The relationship between histopathologic characteristics and treatment outcomes in patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-based immunochemotherapy needs re-evaluation. Patients with newly diagnosed DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were evaluated with respect to clinical characteristics, treatment efficacy, and survival. Immunohistochemistry of bcl-2, CD10, bcl-6, and MUM-1 was performed and patients were sub-classified as germinal center B-cell-like (GCB) or non-GCB type according to the Hans algorithm. There was no significant difference in overall survival (OS) between patients with GCB and those with non-GCB. Although there was no significant difference in OS between high-intermediate and high risk groups as classified by the standard International Prognostic Index (IPI; p = 0.50), all three groups with the revised IPI had a clear-cut separation for event-free survival and OS. The revised IPI better predicted survival than did the standard IPI in patients with DLBCL treated with R-CHOP. The Hans classification had no prognostic value.

Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B‐cell lymphoma treated with R‐CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E‐IPI)

To assess if immunochemotherapy influenced the prognostic value of IPI in elderly diffuse large B-cell lymphoma (DLBCL) patients, we evaluated the performance of the standard International Prognostic Index (IPI) and following modifications: age adjusted (AA)-IPI, revised (R)-IPI, and an elderly IPI with age cut-off 70 years (E-IPI) in patients > 60 years treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). In 267 patients, by IPI/AA-IPI 60% were high-intermediate, 53% high and 12% low risk. With R-IPI, 60% were poor risk and none very good risk. Using E-IPI, 45% were high-intermediate/high risk and 27% low risk. No differences in outcome were seen in the low/low-intermediate groups with IPI/AA-IPI. For E-IPI, failure-free survival (FFS) and overall survival (OS) were significantly different for low/low-intermediate groups. No differences were detected in the four indices with model fit/discrimination measures; however, E-IPI ranked highest. For elderly R-CHOP treated patients, distribution of IPI/AA-IPI skewed toward high/high-intermediate risk with no differences in FFS/OS between low/low-intermediate risk. In contrast, with E-IPI, more are classified as low risk with significant differences in FFS/OS for low-intermediate compared to low risk. The R-IPI does not identify a very good risk group, thus minimizing its utility in this population. The prognostic discrimination provided by the E-IPI for low and low-intermediate elderly DLBCL patients needs validation by other datasets.

Modified Number of Extranodal Involved Sites as a Prognosticator in R-CHOP-Treated Patients with Disseminated Diffuse Large B-Cell Lymphoma

Background/AimsRituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP) has improved survival in patients with diffuse large B-cell lymphoma (DLBCL) and weakened the prognostic power of the international prognostic index (IPI). We evaluated the efficacy of the IPI and revised IPI (R-IPI) in patients with DLBCL who were treated with R-CHOP, focusing on extranodal site number (ENS) because extranodal involvement occurs frequently in Koreans.MethodsA total of 126 R-CHOP-treated patients with stage III/IV DLBCL were analyzed. We performed a retrospective analysis of the clinicopathologic factors and verified the predictive power of the standard IPI and R-IPI. Various numbers of extranodal sites were analyzed for further stratification, and we set the extranodal site-modified IPI (E-IPI) as the IPI when the number of extranodal sites was stratified as < 3 vs. ≥ 3.ResultsA univariate analysis showed that ENS was associated with complete response (CR, p = 0.04), event-free survival (EFS, p = 0.01), and overall survival (OS, p < 0.001) when the ENS cut-off was set at ≥ 3. A multivariate analysis revealed that an ENS ≥ 3 remained associated with EFS (p < 0.01; hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.29 to 5.26) and OS (p < 0.01; HR, 3.52; 95% CI, 1.68 to 7.35). The IPI was effective for determining prognosis in terms of OS (p = 0.04) but not EFS (p = 0.17). The R-IPI was effective in terms of both variables (p = 0.02 and 0.04, respectively), as was the E-IPI (p = 0.01 and 0.001, respectively).ConclusionsAn ENS < 3 vs. ≥ 3, rather than the original < 2 vs. ≥ 2, was the most significant prognostic factor for EFS and OS. All three indices were predictive, but only the E-IPI identified the high-risk group of R-CHOP-treated Korean patients with disseminated DLBCL.