ALBERT

Description: The Iowa Flood Center (IFC), established following the 2008 record floods, has developed a real-time flood forecasting and information dissemination system for use by all Iowans. The system complements the operational forecasting issued by the National Weather Service, is based on sound scientific principles of flood genesis and spatial organization, and includes many technological advances. At its core is a continuous rainfall–runoff model based on landscape decomposition into hillslopes and channel links. Rainfall conversion to runoff is modeled through soil moisture accounting at hillslopes. Channel routing is based on a nonlinear representation of water velocity that considers the discharge amount as well as the upstream drainage area. Mathematically, the model represents a large system of ordinary differential equations organized to follow river network topology. The IFC also developed an efficient numerical solver suitable for high-performance computing architecture. The solver allows the IFC to update forecasts every 15 min for over 1,000 Iowa communities. The input to the system comes from a radar-rainfall algorithm, developed in-house, that maps rainfall every 5 min with high spatial resolution. The algorithm uses Level II radar reflectivity and other polarimetric data from the Weather Surveillance Radar-1988 Dual-Polarimetric (WSR-88DP) radar network. A large library of flood inundation maps and real-time river stage data from over 200 IFC “stream-stage sensors” complement the IFC information system. The system communicates all this information to the general public through a comprehensive browser-based and interactive platform. Streamflow forecasts and observations from Iowa can provide support for a similar system being developed at the National Water Center through model intercomparisons, diagnostic analyses, and product evaluations.

Description: This article presents the data collected and analyzed using the University of Iowa’s X-band polarimetric (XPOL) radars that were part of the spring 2013 hydrology-oriented Iowa Flood Studies (IFloodS) field campaign, sponsored by NASA’s Global Precipitation Measurement (GPM) Ground Validation (GV) program. The four mobile radars have full scanning capabilities that provide quantitative estimation of the rainfall at high temporal and spatial resolutions over experimental watersheds. IFloodS was the first extensive test of the XPOL radars, and the XPOL radars demonstrated their field worthiness during this campaign with 46 days of nearly uninterrupted, remotely monitored, and controlled operations. This paper presents detailed postcampaign analyses of the high-resolution, research-quality data that the XPOL radars collected. The XPOL dual-polarimetric products and rainfall are compared with data from other instruments for selected diverse meteorological events at high spatiotemporal resolutions from unprecedentedly unique and vast data generated during IFloodS operations. The XPOL data exhibit a detailed, complex structure of precipitation viewed at multiple range resolutions (75 and 30 m). The inter-XPOL comparisons within an overlapping scanned domain demonstrate consistency across different XPOL units. The XPOLs employed a series of heterogeneous scans and obtained estimates of the meteorological echoes up to a range oversampling of 7.5 m. A finer-resolution (30 m) algorithm is described to correct the polarimetric estimates for attenuation at the X band and obtain agreement of attenuation-corrected products with disdrometers and NASA S-band polarimetric (NPOL) radar. The paper includes hardware characterization of Iowa XPOL radars conducted prior to the deployment in IFloodS following the GPM calibration protocol.

Description: Background: The International Prognostic Index (IPI) was first described in 1993 and is the most widely used prognostication tool in diffuse large B-cell lymphoma (DLBCL). Five independent risk factors for OS: age (≤60 yrs versus 〉60 yrs), stage (I/II versus III/IV), number of extranodal (EN) sites (≤1 versus 〉1), performance status (PS) (0-1 versus ≥2) and serum lactate dehydrogenase (LDH) (normal versus elevated) were used to design a prognostic model which stratified patients into 4 prognostic groups according to the number of risk factors present: low (0-1), low-intermediate (2), high-intermediate (3), and high-risk (4-5); predicting 5-yr OS rates of 73%, 51%, 43% and 26% and 5-yr relapse-free survival (RFS) rates of 70%, 50%, 49%, 40% respectively. For patients aged ≤60 yrs 3 risk factors (stage, PS and LDH level) remained independently significant for OS, and an age-adjusted (aa) model (the aa-IPI) was proposed which predicted 5-yr OS for the low (0), low-intermediate (1), high-intermediate (2) or high-risk (3) groups of 83%, 69%, 46% and 32% respectively (Shipp et al, 1993). The British Columbia Cancer Agency re-evaluated the role of IPI in the rituximab era in their registry-based cohort of 365 patients in 2007. Although the IPI remained predictive, only 2 (rather than 4) prognostic groups were identified and the authors recommended use of the Revised-IPI (R-IPI) where redistribution of the absolute number of IPI risk factors better stratified patients into 3 prognostic groups: very good (0) good (1,2) and poor (3-5) (Savage et al, 2007). However, a subsequent analysis of pooled data from 3 prospective trials (Ziepert et al, 2010) confirmed that the IPI remained highly predictive of outcomes in the rituximab era. Here we report an evaluation of prognostic indices within the UK NCRI R-CHOP 14 vs 21 prospective trial cohort (Cunningham et al, 2013). Methods: The IPI and R-IPI were applied to the R-CHOP 14 versus 21 trial cohort (n=1,080) and for the subgroup of patients aged ≤60 yrs (n=515) and correlated with OS and progression-free survival (PFS). For patients aged ≤60 yrs the aa-IPI was applied in addition. It was not possible to evaluate the NCCN-IPI in our cohort as absolute LDH values were not collected at enrolment. The association between baseline clinical factors (age, gender, PS, stage, presence of 〉1 EN site of disease, presence of an elevated LDH, disease bulk and B symptoms) and patient outcomes were investigated in univariable and multivariable analysis (MVA). Performance of the prognostic indices was compared using the Concordance Probability Estimate (CPE) and Akaike's Information Criterion (AIC): CPE evaluates discriminatory power to assess the strength of statistical models (higher values indicate better discrimination); AIC estimates the quality of statistical models relative to each other in terms of fitting the data (lower values indicate a better model fit). Results: After a median follow-up of 6.5 years, both the IPI and R-IPI were significantly associated with OS (Figure 1) and PFS; the IPI performed better than the R-IPI for OS and PFS in terms of discrimination and model fit (Table 1). All IPI factors were significantly associated with OS, and remained in MVA with the exception of disease stage. For patients aged ≤60 yrs, the IPI, R-IPI and aa-IPI were all strongly associated with OS and PFS; the IPI performed best overall of the 3 prognostic indices in terms of discrimination and model fit (Table 2). All individual IPI risk factors, excepting stage, were again found to be significantly associated with OS in MVA for patients aged ≤60 yrs. Conclusion: For the entire DLBCL cohort both the IPI and R-IPI identified meaningful prognostic groups for OS and PFS. Although the IPI outperformed the R-IPI, neither index identified a patient subgroup with an OS of

Description: Introduction: The discovery of 3 distinct molecular subgroups of diffuse large B-cell lymphoma (DLBCL) according to cell-of-origin (COO): germinal centre B-cell (GCB), activated B-cell (ABC) and type III/unclassifiable by gene expression profiling (GEP) (Alizadeh et al, Nature 2000; Rosenwald et al, NEJM 2002) was a key advance in understanding the disease biology. The ABC subtype is associated with inferior survival which has persisted in the rituximab era (Lenz et al, NEJM 2008). Determination of COO by GEP has not been incorporated into routine practice however due to a lack of accessibility and requirement for fresh frozen tissue. Barrans et al (BJH 2012) recently demonstrated that COO could be accurately classified by the Illumina DASL® platform, using RNA extracted from routinely processed FFPE tissue from a population-based cohort of 172 R-CHOP-treated patients, and predicted clinical outcome. The aim of this analysis was to determine GEP-based DLBCL COO using the Illumina DASL® platform, to correlate results with outcome, and to validate this methodology using FFPE tissue samples from patients enrolled in the prospective phase III R-CHOP 14 v 21 trial. Methods: The UK NCRI R-CHOP-14 v 21 trial assessed R-CHOP given 2-weekly versus 3-weekly in 1080 previously untreated DLBCL patients aged ≥18 years and enrolled from 2005-2008. We previously reported that R-CHOP-14 was not superior to R-CHOP-21 for overall survival (OS), progression-free survival (PFS), response rate or safety. COO as determined by the Hans classifier (n=560) was not prognostic for OS (Cunningham et al, Lancet 2013). All patients with sufficient FFPE material remaining were included in this analysis. RNA was extracted and GEP was performed using the Illumina DASL® platform. Cases were classified as ABC, GCB or type III according to the DAC classifier (Care et al, Plos One 2013). Response was assessed using IWG 1999 criteria. PFS and OS were calculated from date of randomisation and analysed using Kaplan-Meier and Cox regression methods. Results: 369 patients had sufficient FFPE material remaining for analysis. COO classification was as follows: ABC 15.2% (n=56), GCB 46.3% (n=171), type III 38.5% (n=142). Baseline characteristics are shown in Table 1. Patients with GCB subtype had a significantly higher incidence of BCL-2 (p1 extranodal site of disease, elevated LDH), sex, bulky disease, B symptoms and trial arm; patients classified as GCB or type III had superior OS versus ABC subtype (HR 0.53, 95% CI: 0.31-0.89; p=0.02) and (HR 0.56, 95% CI: 0.33-0.96; p=0.03) respectively. GCB subtype was also independently associated with superior PFS versus ABC subtype (HR=0.59, 95% CI: 0.37-0.96; p=0.03). The difference in PFS between type III and ABC subtypes did not reach statistical significance, but followed a similar trend (HR=0.65, 95% CI: 0.40-1.07; p=0.09). Results of univariate and multivariate analyses of individual factors and OS are shown in Table 2. Conclusion: Our results demonstrate that the ABC subtype of DLBCL as determined by GEP is independently associated with inferior PFS and OS. Our findings confirm those of Barrans et al (BJH 2012) and serve as a validation cohort for this methodology in the setting of a prospective trial where patients were exclusively R-CHOP-treated. Of note our patient cohort included a high proportion of type III/unclassifiable patients (38.5%) which are being further investigated currently and updated results will be presented at the meeting. Our analysis confirms that GEP-based COO is a significant prognostic biomarker for DLBCL in the rituximab era which can be accurately determined using routinely processed FFPE tissue samples. Table 1 Baseline characteristics Table 1. Baseline characteristics Figure 1. Overall survival by cell-of-origin determined by gene expression profiling group Figure 1. Overall survival by cell-of-origin determined by gene expression profiling group Table 2 Overall survival: univariate and multivariate analyses Table 2. Overall survival: univariate and multivariate analyses Disclosures Cunningham: Medimmune: Research Funding; Merrimack: Research Funding; Celgene: Research Funding; Bayer: Research Funding; Astra-Zeneca: Research Funding; Amgen: Research Funding. Hawkes:Merck Serono: Research Funding; Takeda: Other: travel expenses; BMS: Other: travel expenses, Research Funding. Pocock:Gilead Sciences: Other: Sponsorship to attend the EHA 2016 Meeting; Janssen: Speakers Bureau; Takeda: Honoraria. Ardeshna:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Conference Expenses, Research Funding. Radford:Astra Zeneca: Equity Ownership; GlaxoSmithKline: Equity Ownership; Novartis: Honoraria; Seattle Genetics: Honoraria; Takeda: Honoraria, Research Funding.

Description: Introduction: DLBCL subtypes may be classified by gene expression corresponding to germinal centre (GCB) or activated peripheral blood (ABC) B-cells. Treatment outcomes with R-CHOP therapy were inferior for ABCs in retrospective series, and this study investigated whether adding bortezomib could reverse the adverse prognosis. The trial used gene expression profiling (GEP) to stratify cases, with adaptive design to analyse the outcome by subtypes at predefined timepoints. Methods: Newly diagnosed patients with DLBCL underwent staging and commenced standard R-CHOP. During cycle 1, formalin-fixed paraffin-embedded (FFPE) tissue was used to extract messenger RNA for GEP using the Illumina DASL array platform. Cases were allocated to GCB, ABC or Unclassifiable (Unc) type before starting cycle 2, using an established algorithm based upon 20 genes. Patients with successful GEP were randomised 1:1 to receive R-CHOP +/- bortezomib 1.6 mg/m2 s/c on days 1+8 in cycles 2-6. The study was powered to detect a difference in progression-free survival (PFS) of 10% with bortezomib, with a 2-sided significance, 5% and 90% power. The adaptive design allowed for closure of randomization for GCB cases if 1-year PFS was 10cm 17 26 21 Conclusions: This study has demonstrated the feasibility of GEP at diagnosis to subsequently guide therapy in a large multicentre trial. Although patients with ABC type lymphoma were in general slightly older, they did not appear to have other adverse prognostic features at diagnosis vs GCB. All patients will have completed therapy by the time of the meeting, allowing the initial response and toxicity data to be available for presentation. Disclosures Davies: GIlead: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; CTI: Honoraria; Takeda: Honoraria, Research Funding; Bayer: Research Funding; GSK: Research Funding; Janssen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Pfizer: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: The addition of bortezomib to R-CHOP chemotherapy in diffuse large B-cell lymphoma. Pocock:Janssen: Honoraria. Jack:Jannsen: Research Funding. Johnson:Takeda: Honoraria; Pfizer: Honoraria; Janssen: Research Funding.

Description: Abstract 1621 The outcome for children with Hodgkin's Lymphoma treated using the German-Austrian paediatric risk-adapted combined modality regimen appears superior to that of adults treated with ABVD +/− radiotherapy. Whether this is related to the superiority of the therapy or a biological difference in the disease in the different age groups is unclear. As a preliminary step to try and compare these regimens directly we enrolled 47 patients between 18 and 30 years of age (median 23y range 18–30) recruited from 8 centres across the UK onto the 18–30 study which used a modified version of the HD95 protocol. Patients were allocated to one of three treatment groups according to stage TG1=1A, 1B, 2A (n=16), TG2=2AE, 2B, 3A (n=11) TG3=2BE, 3AE, 3BE, 3B, 4A, 4B (n=20). Patients in TG1 received 2 cycles of OEPA (vincristine 1.5mg/m2 iv d1,d8,d15 (capped at 2mg/dose), etoposide 125mg/m2 iv d1–5, adriamycin 40mg/m2 iv d1 & 15, prednisolone 60mg/m2 po d1–15). Patients in TG2 received 2xOEPA and 2 xCOPP (cyclophosphamide 500mg/m2 iv d1 and 8 vincristine 1.5mg/m2 iv d1,8 (capped 2mg/dose) procarbazine 100mg/m2 po d1–15, prednisolone 40mg/m2 po d1–15). Patients in TG3 received OEPAx2 and COPPx4. All patients (except those in TG1 who were in CR by CT and PET criteria) went on to receive involved site radiotherapy to all sites of previous disease. The dose of radiotherapy was 20Gy for patients in CR and VGPR (〉75% reduction) by CT criteria with areas of residual abnormality on scan 〉50ml receiving a 30Gy boost. Patients with a PR (50–75% reduction) received the same doses if they were PET negative however those who were PET positive received 30Gy to all sites of previous disease. The schedule of vinca alkaloids in HD95 is compressed with those in TG3 receiving 16 doses of vincristine 1.5mg/m2 (max 2mg) given over 6 months compared with 16 doses of vinblastine 6mg/m2 given over 8 months in ABVD. In view of this and the increase in vinca alkaloid related neurotoxicity with age the primary endpoint of this study was to establish the level of neurotoxicity using this paediatric regimen in young adults. 45 patients (23 male) completed therapy. 1 patient was withdrawn after a hypersensitivity reaction to etoposide on d1 OEPA1 and 1 patient withdrew consent prior to starting therapy. Worst neurotoxicity grade was recorded as: 0 (n=8), 1 (n=17), 2 (n=16) 3 (n=4 [with 2 motor in TG1 &TG2, 1 sensory inTG2, 1 ileus inTG3). In 3 of the 4 patients with severe neurotoxicity vincristine was converted to vinblastine 6mg/m2 according to protocol. No progression of the neuropathy was seen and patients were able to complete their scheduled therapy. In one case (TG2) vincristine was omitted in the final cycle. Neurotoxicity grade at last FU was 0 (n=34) 1 (n=8) 2 (n=3). All 4 cases of grade 3 neurotoxicity reverted to grade 0. Seven patients with grade 2 neuropathy had adjustments made to the dose or type of vinca alkaloid at the request of the physician. Current grade of neuropathy at last FU in these 7 patients:0 (n=4) 1 (n=2) 2 (n=1). There were 8 episodes of febrile neutropenia. Other grade 3 toxicities included diarrhoea (n=2), vomiting (n=3), mucositis (n=3), abdominal pain (n=3) and thrombosis (n=2). Bone/joint pain was seen in 4 patients. Two patients (both TG3) have developed proven osteonecrosis. All 45 patients who completed the chemotherapy achieved a CR or PR. Four did not require radiotherapy, 36 required 20Gy and 5 required 30Gy as a baseline dose to previously involved sites. The median follow up to date is 18 months. Four patients have progressed (1=TG2, 3=TG3) giving a 2yr PFS of 89%. All patients are currently alive. Quality of life data has been collected and assessments of late effects are ongoing. In conclusion, young adults aged 18–30 can tolerate a modified HD95 protocol with a minority of patients experiencing grade 3 neurotoxicity which is reversible when adjustments are made. Outcome with this regimen (which contains only 160mg/m2of adriamycin and no bleomycin) seems encouraging and this (or a more up to date German Austrian Paediatric protocol e.g.with dacarbazine replacing procarbazine in an attempt to spare fertility and omission of radiotherapy based on PET scan after OEPA) warrants testing against ABVD in this age group. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 440 Background: Rituximab is widely used in combination with chemotherapy for treating B cell lympho-proliferative disorders. In MCL, two randomised trials explored the addition of Rituximab to standard initial therapy. Neither demonstrated a significant improvement in either PFS or OS. In 2002 the NCRN initiated a phase II randomised trial of FC chemotherapy with or without Rituximab to evaluate response rates. In 2006 this was extended to a phase III study with overall survival as the primary end point. Trial: Newly diagnosed patients with MCL requiring therapy received up to 8 cycles of oral FC (Fludarabine 40mg/m2 and Cyclophosphamide 250mg/m2 both daily × 3) given every 4 weeks with a randomisation to the addition of Rituximab 375mg/m2 on day 1. There was no age limit to the study, no risk stratification and no consolidation of responses with transplantation or maintenance therapy. Results: 370 patients were randomised. Median age was 66 years (range 36 – 88) with 76% male patients. The arms were well balanced by Mantle Cell International Prognostic Index (MIPI); 77% in the FCR arm and 71% in the FC arm were in the intermediate or high risk groups. 78% and 72% respectively received 4 or more cycles of FCR/FC. At the end of treatment the ORR was 90.6% in the FCR arm and 79.8% in the FC arm (p = 0.01) with CR + CRu rates of 64.7% and 46.9% (p = 0.002) respectively. 5.8% of patients in the FCR arm and 11.9% in the FC arm had PD at the end of treatment. Patients in the FCR arm had longer progression free and overall survival with HRs of 0.56 (95% CI: 0.43–0.73, p 〈 0.001) and 0.72 (95% CI: 0.54–0.97, p = 0.03) respectively. At a median follow up of 38.8 months the median PFS is 30.6 months in the FCR arm and 16.1 months in the FC arm. The median OS is 45.7 months for FCR and 37 months for FC. The major toxicities were haematological. Significantly more patients in the FCR arm experienced grade 3 or 4 Leucopoenia and Thrombocytopenia however the numbers of grade 4 were not significantly different. Combined grade III/IV toxicity showed 23.3% thrombocytopenia, 45.8% leucopoenia, 12.9% anaemia and 51.4% neutropenia. 11.8% of patients had significant infections. Renal toxicity was modest. 1 patient experienced grade III but there was no grade IV toxicity. Lymphoma was the commonest cause of death, but 29% of patients in the FCR arm and 24% in the FC arm died of other causes, of which almost half were infection related. An additional 11 patients died of a second malignancy, 4 of whom had AML. 14% of patients in the FCR arm and 10% in the FC arm died without evidence of disease progression. Conclusion: The addition of Rituximab to FC chemotherapy leads to a significant improvement in both PFS and OS with an acceptable level of additional toxicity. A significant number of patients treated with FC based chemotherapy die whilst in remission of non lymphoma related causes. Disclosures: Rule: Roche: Consultancy, Research Funding. Off Label Use: Rituximab in mantle cell lymphoma. Follows:Roche: Consultancy, Honoraria. Hillmen:Roche Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKine: Honoraria, Speakers Bureau; Genzyme: Research Funding; MundiPharma: Honoraria, Speakers Bureau. Walewski:Janssen-Cilag: ; Hoffman La Roche: Honoraria, Institutional/personal grants, travel/accommodation expenses; Mundipharma: Honoraria; Celgene: Honoraria.

Description: 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. Disclosures Cunningham: 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.

Description: Introduction: Primary Mediastinal B-cell Lymphoma (PMBL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) comprising approximately 10% of cases. Studies in the pre-rituximab (R) era suggested a benefit for dose intensified regimens such as V/MACOP-B over cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). However no prospective studies comparing dose intensified regimens with R-CHOP have been performed in the rituximab era and controversy exists regarding the current optimal induction chemotherapy. R-CHOP +/- involved field radiotherapy (IFRT) is the most commonly used regimen worldwide with reported 5-yr relapse free and overall survival rates of 68-81% and 79-91% respectively; but with the exception of the MInT trial (which evaluated young patients with PMBL aged ≤60 years with an age-adjusted International Prognostic Index of 0-1), the evidence for R-CHOP in PMBL comes from retrospective studies. The aim of this analysis was to evaluate the outcomes for R-CHOP treated PMBL patients within the UK NCRI R-CHOP 14 v 21 prospective trial. Methods: The phase III randomised UK R-CHOP-14 vs 21 trial assessed R-CHOP given 2 weekly versus 3 weekly in 1080 DLBCL patients aged ≥ 18years who were enrolled from 2005-2008. We previously reported that R-CHOP-14 was not superior to R-CHOP-21 for overall survival (OS), progression free survival (PFS), response rate or safety (Cunningham D et al, Lancet May 2013). Patients with PMBL were not excluded from participation and we identified cases by searching the trial database for patients with a mediastinal mass (≥5cm) who also fulfilled the WHO 2008 clinical criteria for sites of involvement (absence of disease involvement outside of the thorax +/- cervical / supraclavicular lymph node involvement). Response was assessed according to the IWG 1999 criteria. PFS and OS were calculated from date of randomisation and analysed using Kaplan-Meier methods. Results: 50/1,080 (4.6%) patients from the R-CHOP 14 v 21 study database met the WHO 2008 criteria for PMBL and were included in this analysis, with a median follow-up of 7.3 years. The median age at diagnosis was 38.5 years (range 22-78 years). 50% (n=25) of the patients were female. All patients had stage I (n=18, 36%) or II (n=32, 64%) disease. The median mediastinal mass diameter was 11.1cm (range 6-23cm) and 70% (n=35) of patients had a mediastinal mass ≥10cm. 28 (56%) and 22 (44%) patients were treated with R-CHOP-21 and R-CHOP-14 respectively. On completion of R-CHOP chemotherapy CT response was complete (CR) in 43% (n=21), partial (PR) in 49% (n=24), stable disease (SD) in 2% (n=1) and progressive disease (PD) in 6% (n=3), one patient was non-evaluable. IFRT was administered to 58% of patients (n=29). For all patients (n=50) the 5-year PFS was 80.0% (95% CI 68.7-91.1) and 5-year OS was 84.0% (95% CI 73.8-94.2), as shown in Figures 1 and 2 respectively. 5/10 PFS and 4/9 OS events occurred in patients who had received consolidation IFRT post R-CHOP. Where disease progression occurred 9/10 events occurred within the first-year of follow-up. Conclusion: Our data confirms the efficacy of R-CHOP in the management of PMBL and is a benchmark for future studies in PMBL. This is to our knowledge, the largest reported cohort of R-CHOP treated PMBL patients from a prospective trial. The strength of this analysis lies in the long duration of follow-up, the strict selection of patients according to the WHO 2008 criteria and the inclusion of all patients ≥ 18 years without an upper age limit. In line with previous studies we found that disease progression in PMBL occurs early and late relapses are rare. Over half of the patients in our analysis (58%) received consolidation IFRT following R-CHOP. Response assessment by FDG-PET-CT on completion of R-CHOP was not mandated by the study protocol and whether IFRT could have been avoided for PET negative patients in our cohort is unknown. The currently accruing IELSG 37 prospective trial will help to address this important clinical question in PMBL. Excellent results have recently been reported with the combination of DA-EPOCH-R in PMBL, but the efficacy of such dose-intensified regimens in comparison to R-CHOP needs to be evaluated in prospective randomised studies. Figure 1. Progression Free Survival (n=50) Figure 1. Progression Free Survival (n=50) Figure 2. Overall Survival (n=50) Figure 2. Overall Survival (n=50) Disclosures Cunningham: Amgen: Research Funding; Astra Zeneca: Research Funding; Merck Serono: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Merrimack: Research Funding; Medimmune: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding. Pocock:Janssen: Honoraria.