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Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI ≥80%, 33% were hospitalized with ≥1 infections compared with 23.3% of 355 patients receiving an IDI of 80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score ≥6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin >36 g/L, CIRS-G score

Funder: Oxford Experimental Cancer Centre, Background: This Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity. Methods: Patients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils < 1.5 × 109/L, platelets < 75 × 109/L, ECOG > 1. Baseline HR23B expression was assessed by immunohistochemistry. Results: Fifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3–4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2–5.4) in solid-organ cancers and 2.6 months (95%CI 1.2–5.6) in lymphomas. HR23B status did not predict response. Conclusions: CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted. Trial registration: ClinicalTrials.gov identifier NCT01977638. Registered 07 November 2013.

Central nervous system (CNS) relapse following R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) occurs in 2-5% of patents with diffuse large B-cell lymphoma (DLBCL). Many patients aged ≥70 years are unsuitable for high-dose methotrexate (HDMTX) prophylaxis and therefore often receive stand-alone intrathecal prophylaxis. The CNS international prognostic index (CNS-IPI) is a clinical CNS relapse risk score that has not specifically been validated in elderly patients. The value of CNS prophylaxis in patients aged ≥70 years remains uncertain. Data on 690 consecutively R-CHOP-treated DLBCL patients aged ≥70 years were collected across 8 UK centres (2009-2018). CNS prophylaxis was administered per physician preference. Median age was 77·2 years and median follow-up was 2·8 years. CNS-IPI was 1-3 in 60·1%, 4 in 23·8%, 5 in 13·0% and 6 in 3·3%. Renal and/or adrenal (R/A) involvement occurred in 8·8%. Two-year overall CNS relapse incidence was 2·6% and according to CNS-IPI, 1-3:0·8%, 4:3·6%, 5:3·8% and 6:21·8%. Two-year CNS relapse incidence for R/A was 10·0%. When excluding HDMTX (n = 31) patients, there remained no change in unadjusted/adjusted CNS relapse for intrathecal prophylaxis effect according to CNS-IPI. CNS-IPI is valid in elderly R-CHOP-treated DLBCL patients, with the highest risk in those with CNS-IPI 6 and R/A involvement. We observed no clear benefit for stand-alone intrathecal prophylaxis but observed an independent increased risk of infection-related admission during R-CHOP when intrathecal prophylaxis was administered.

Background The increasing incidence of diffuse large B‐cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co‐morbidity, frailty, and reduced organ and physiological reserve contribute to treatment‐related complications. The optimal dose intensity of R‐CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. Objectives and Methods We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009–2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. Results Progression‐free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70–79 years (P < 0.001). In contrast, 2‐year cumulative relapse incidence, when accounting for non‐relapse mortality as a competing risk, was no different between 70–79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS‐G: 0–6 vs. >6) (P = 0.27). In 70–79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI 80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). Conclusion ‘R‐mini‐CHOP' provides adequate lymphoma‐specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.

Diffuse large B-cell lymphoma (DLBCL) and osteoporotic fracture are both more common in older patients. Exposure to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) is likely to increase the risk of fracture, but evidence is lacking to define fracture incidence in this group. Data on consecutive patients with DLBCL aged ≥70 years treated with 1 to 8 cycles of full or attenuated R-CHOP were retrospectively collected across 10 UK centers (2009-2019). Patients were followed up from starting R-CHOP for a minimum of 6 months and censored at 18 months; at last follow-up if

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within.

Introduction Diffuse large B cell lymphoma (DLBCL) and osteoporotic fracture are commoner in older patients (pts). Steroids and chemotherapy are recognised as a risk factor (RF) for fragility-related fracture and its associated morbidity. A small randomised trial (RCT) (Westin 2013) showed bisphosphonates stabilize bone mineral density (including all ages / histologies) in NHL pts. Despite this, there is a lack of data defining the specific incidence and fracture risk in older DLBCL pts post R-CHOP. We aimed to better define this risk in this specific cohort. Methods Data on consecutive DLBCL pts ≥70 years (y) treated with R-CHOP were retrospectively collected across 7 UK centres (2009-2019). Follow up was censored in 07/2019. All pts had untreated, de novo DLBCL or untreated transformed (to DLBCL) indolent B cell NHL. PTLD, HIV and pre-treated NHL pts were excluded. All pts received 1-9 cycles of full or attenuated R-CHOP with curative intent. Pts were excluded if they had progressive disease (PD) or died < 6 months (m) of cycle 1 R-CHOP (RCHOP1). A detailed anonymised database included ECOG performance status (PS), body mass index (BMI), history of osteoporosis / osteopenia, documented steroid pre-phase, vitamin D supplementation, calcium and alkaline phosphatase levels, and sites of bone DLBCL involvement. Fractures at diagnosis (DLBCL-related/unrelated) and pre diagnosis were collected. Fractures (including bone site) occurring during 18m from RCHOP1 were identified from radiology records. Pts were followed for a minimum of 6m and censored at 18m from RCHOP1, or at their last follow up if < 18m or at PD or death if between 6-18m. Baseline pt characteristics were descriptive. Survival analyses were performed using Kaplan Meier methods and Cox regression with comparisons between categories using the log-rank test. Time to event analyses were measured from RCHOP1 until fracture event. Primary end point was 18m cumulative fracture incidence censoring pts at death or relapse. Univariable and multivariable analyses (UVA; MVA) of potential influencing RFs for fracture was assessed by Cox regression (Final stepwise model; p=0.1 for inclusion). Results Of 589 pts identified, 92 pts had PD or died prior to 6m and were excluded. 20 pts were excluded due to short follow up. Across 477 pts, the median age was 77 (range 70-93) y. 66% had an ECOG PS 0-1. The median cycles given was 6 (range 1-9). 27.3% received pre-phase steroids. The median BMI was 25.5 (range 14.2-48.1). 8.1% had a fracture prior to DLBCL, and 9.1% had a history of osteopenia or osteoporosis. 5.7% were current smokers, 3% had rheumatoid arthritis, 13.5% had type (T) 2 diabetes (DM), and 4.5% had a history of excess alcohol. At baseline, 25.2% had PET or CT-assessed cortical bone involvement. Overall, there were 52 fractures, including 50 within 18m follow up. Cumulative fracture incidence was 6.3% (95% confidence interval (CI) 4.4 - 8.9) at 6m, 9.5% (95% CI 7.1 - 12.6) at 12m and 11.5% (95% CI 8.8 - 14.9) at 18m (Fig A). 6 pts had multiple fracture sites (2; n=5, 3; n=1). 32 (62%) had vertebral fracture(s). Thoracic (34% 20/59) and lumbar vertebral (27% 16/59) were dominant sites (Fig C). 7/52 fractures were at the site of DLBCL involvement, 17/52 were at a different site from initial bone DLBCL involvement, 27/52 were in pts without bone involvement and 1/52 was unknown. Univariable RFs included female sex (hazard ratio (HR) 1.89 (95% CI 1.05 - 3.28)), known osteopenia or osteoporosis (HR 2.64 (95% CI 1.32 - 5.29)), DLBCL-related fracture at diagnosis (HR 4.05 (95% CI 2.07 - 7.92) (Fig B). Initial bone involvement was only associated with an increased risk in pts with a DLBCL-related baseline fracture (95% CI HR 4.56 (2.27 - 9.17)) (Table 1). MVA showed that DLBCL-related baseline fracture (HR 4.32 (1.97 - 9.47)) was the only significant independent RF for fracture with low BMI (p=0.051) and smoking history (p=0.052) of borderline significance (Table 2). Conclusions This is the largest series to date to show there is a clinically relevant fracture risk in older DLBCL pts specifically receiving R-CHOP in early follow up. Our data have limitations inherent to a retrospective study including the potential for unknown confounders, missing data, and medical record misinterpretation. Prospective data is required to validate RFs identified which could enable targeting a high-risk population. An RCT is needed to determine the value of prophylactic intervention(s) in high risk pts. Figure Disclosures Gibb: Takeda: Research Funding. Collins:Gilead: Consultancy, Honoraria. Eyre:Janssen: Honoraria; Abbvie: Honoraria; Gilead: Consultancy, Honoraria, Other: commercial research support; Roche: Honoraria.

The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear. Both patient groups had similarly dysfunctional aggregation responses to collagen and collagen-related peptide, and comparison with mechanistic experiments in which platelets from healthy donors were treated with the Btk inhibitors suggested that both drugs inhibit platelet Btk and Tec at physiological concentrations. Only ibrutinib caused dysfunctional thrombus formation, whereas size and morphology of thrombi following acalabrutinib treatment were of normal size and morphology. We found that ibrutinib but not acalabrutinib inhibited Src family kinases, which have a critical role in platelet adhesion to collagen that is likely to underpin unstable thrombus formation observed in ibrutinib patients. We found that platelet function was enhanced by increasing levels of von Willebrand factor (VWF) and factor VIII (FVIII) ex vivo by addition of intermediate purity FVIII (Haemate P) to blood from patients, resulting in consistently larger thrombi. We conclude that acalabrutinib avoids major platelet dysfunction associated with ibrutinib therapy, and platelet function may be enhanced in patients with B-cell NHL by increasing plasma VWF and FVIII.

Introduction Very few studies have assessed the incidence and risk factors associated with CNS progressive disease (PD) in elderly DLBCL. The CNS IPI (international prognostic index) uses the standard IPI with an additional point for renal/adrenal (R/A) involvement to define CNS risk in DLBCL patients (pts). The CNS IPI is validated in younger DLBCL pts (Schmitz et al, 2016) but little is known about CNS risk in the elderly. Few data exist outwith a single study of pts >80 years (y) pooled from 2 LYSA mini CHOP trials (Cabannes-Hamy et al 2018). CNS PD risk from 270 pts >80y was 1.8% at 2y and 3% overall. CNS PD risk did not differ according to CNS IPI in this study. No real world data outside of these trials exists. Few studies have assessed the risk of CNS prophylaxis (intrathecal (IT) +/- high dose intravenous (IV) methotrexate (HDMTX)) in the elderly. Methods Data on consecutively treated new DLBCL pts ≥70y were retrospectively collected across 6 UK centres (2009-2018). We compiled a detailed database of CNS-IPI, extranodal disease sites, CNS prophylaxis, adverse events related to IV HDMTX, rate and timing of CNS PD, outcome post CNS PD and associations with CNS PD risk. Results 529 pts received Rituximab (R) chemotherapy with curative intent (513 R-CHOP/attenuated R-CHOP (97.0%), 13 R-PMitCEBO, 3 R-GCVP). 80.7% (427/529) received no CNS prophylaxis, 14.7% (78/529) received intrathecal (IT) MTX prophylaxis, 2.1% (11/529) received HDMTX only, and 2.5% (13/529) received both IV HDMTX and IT MTX. The median age of all pts was 76.7y and median follow up 2.9y (range 0.4 - 10.9y). The CNS IPI was 1 in 11.8% (60/510), 2 in 21.2% (108/510), 3 in 24.3% (124/510), 4 in 26.1% (133/510), 5 in 12.9% (66/510) and 6 in 3.7% (19/510). 19 pts were unclassifiable due to a missing LDH (Table 1). Extranodal sites (ENS) were noted in 64.7% (342/529). Median ENS were 1 (range 0-5). Commonest sites were bone 24.2% (128/529), liver 9.6% (51/529), renal 7.6% (40/529), and gastric/oesophageal 7.0% (37/529). R/A involvement was present in 9.3% (49/529). Pts with higher CNS IPI were more likely to receive CNS prophylaxis (IT and/or MTX); CNS IPI 0-1; 13.3%, 2-3; 10.9%, 4+; 29.9% (p Of 24 pts receiving IV HDMTX, median age was 72.4y, mean CNS IPI 3.6 (median 4), and median eGFR 83 (range 47 - 90) ml/min/1.73m2. 21% (5/24) were readmitted with complications directly post HDMTX (Neutropenic fever (NF) (n=1), non-NF (n=1), mucositis (n=1), pericarditis (n=1), and pneumonia/SIADH (n=1)). A single CNS PD occurred in this cohort (4.2%). When pts that received IT MTX were compared to pts receiving no IT MTX, the readmission rate during R-chemo with all-cause infection was 53.8% (42/78) vs 25.9% (105/405; 22 unknown) (p The overall rate of CNS PD was 2.7% (14/527). These included isolated CNS PD (n=11) and concurrent CNS and systemic PD (n=3). The rate of CNS PD was 2.2% (4/178 including (1 concurrent relapse)) in ≥80y and was not statistically different at 2.9% (10/349 including 2 concurrent PD) in 70-80y (p=0.87). 71% (10/14) CNS PD had a CNS IPI 4-6. 12/14 of CNS PD occurred The rate of CNS PD according to CNS IPI was: CNS IPI 1-3: 1.3% (4/300), CNS IPI 4: 2.3% (3/133), CNS-IPI 5: 4.5% (3/66) and CNS IPI 6: 21.1% (4/19) (CNS IPI 4-6: 4.6% (10/218)). CNS PD risk with R/A involvement was 8.2% (4/49). Significant Univariate risk factors for CNS PD include higher CNS IPI, ECOG 3-4, ≥2 ENS and R/A involvement as higher risk pts (Table 1). The overall survival (OS) post CNS PD (CNS only) was short (median of 2.7 months (m) (range 23 days - 8.6 m)) which was similar to OS of systemic PD (median 3.3 m) (Fig D). Conclusions The rate of CNS PD in elderly pts receiving RCHOP or RCHOP-like treatment is low and consistent with LYSA data. There were no differences in CNS PD incidence in 70-80y vs ≥80y. Increase risk was particularly apparent in CNS IPI 5-6 and R/A involvement. IV HDMTX in ≥70y was associated with a 21% readmission rate and its benefit is unclear. Readmission with infection was statistically higher in those receiving IT MTX although this is confounded by higher IPI in these pts. Prophylaxis requires a careful risk assessment in the elderly, evaluation of individual pt factors and consideration of the risks. On the basis of these data, consideration of prophylaxis should be confined to CNS IPI 5-6 and/or R/A involvement. Disclosures Eyre: Celgene: Other: travel support; Janssen: Consultancy, Other: travel support; Roche: Consultancy; Abbvie: Consultancy, Other: travel support; Gilead: Consultancy, Other: travel support. Djebbari:Celgene: Honoraria, Other: travel support, Research Funding; Takeda: Honoraria, Other: travel support; Pfizer: Other: conference registration. McMillan:Celgene: Honoraria, Other: travel support; BMS: Honoraria; Amgen: Honoraria; Takeda: Other: travel support; Roche: Consultancy, Honoraria, Other: travel support; Pfizer: Research Funding; MSD: Honoraria. Bishton:Abbvie: Research Funding; Roche: Research Funding; Takeda: Other: travel support to ASH; Gilead: Research Funding. Fox:Roche: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: travel support, Speakers Bureau; Sunesis: Consultancy; Gilead: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Abbvie: Consultancy, Other: travel support, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: travel support, Speakers Bureau. Collins:ADC Therapeutics: Consultancy, Honoraria, Research Funding; Celgene Corporation: Research Funding; Amgen: Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau; Celleron: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria.

Introduction The impact of RCHOP dose attenuation in elderly patients (pts) with DLBCL is poorly understood. 1% of DLBCL 1st line pts in trials are ≥80 years (y). Attenuated R-CHOP (25mg/m2 doxorubicin (DOX); 400mg/m2 cyclophosphamide (CYCLO), 1mg vincristine) cure 50-60% in phase II trials (Peyrade et al, 2011, 2017). Full dose RCHOP compared to attenuated RCHOP does not improve outcome in ≥80y (Juul et al, 2018) or may worsen survival via toxicity (Eyre et al, 2016, Carson et al 2015). Methods We systematically collected data on IDI (cycle (C)1 dose) and RDI of CYCLO/DOX in consecutively treated pts ≥70ys across 6 UK centres (2009-18). Untreated de novo DLBCL and untreated transformation (HGT) of indolent NHL (iNHL) receiving ≥C1 were included. RCHOP was given at a minimum interval of 21 days. G-CSF was routine. The following were excluded: HIV+, prior solid organ transplant, isolated leg type DLBCL, pre-treated HGT, central nervous system involvement with DLBCL, and pts unfit for anthracycline. Data were collected on Cumulative Illness Rating Scale for Geriatrics (CIRS-G), CIRS-G severity index (total/no. categories), age-adjusted international prognostic index ((aa)IPI), Hb, albumin, LDH, B symptoms, bulk ≥10cm, major operation at diagnosis, and extranodal sites (ENS). Predictors of progression free (PFS), disease free (DFS), and overall survival (OS), were determined using univariable (UVA) and multivariable (MVA) Cox regression. Factors were analysed as continuous (denoted *); additionally IDI (full dose: ≥80% of weight based dose vs attenuated: Results 511 pts received R-CHOP with curative intent. 49% were male and 51% were female. Median follow up was 1.67y. Median age was 77y. 32% had stage I-II and 68% stage III/IV. 14% had concurrent iNHL, 20% bulk, 33% >1 ENS, and 66% IPI 3-5. 46% had CIRS-G ≥6. When comparing age/IDI categories, in 70-80y, pts with IDI80% (2-4; 30%), higher IPI 3-5 (71% vs 64%), higher CIRS-G≥6 (59% vs 40%), and higher CIRS-G severity index. ≥80y receiving IDI>80% had better ECOG (0-1 67% vs IDI For all pts, median PFS was 5.4y (95% confidence interval (CI) 4.1 - 6.9), median DFS was not reached, and median OS 5.5y (95% CI 4.5 - 6.7). When analysed by 70-80 vs ≥80y: 2y PFS was 71.8% (95% CI 66.4-76.4%) vs 60.3% (95% CI 51.5-68.0%), 2y DFS 79.4% (95% CI 74.3-83.6%) vs 76.7% (95% CI 68.4-83.1%) (p = 0.23) and 2y OS 74.6% (95% CI 69.4-79.1%) vs 60.2% (95% CI 51.2-68.1%). Unlike OS and PFS, DFS was not significantly different when 70-80y vs ≥80y were compared, suggesting >80y have a worse outcome due to toxicity and/or unrelated causes of death. 15 deaths in >80y with IDI>80 were: infection (n=5), systemic progressive disease (PD) (n=7), CVA leading to stopping RCHOP post C1 (subsequent PD) (n=1), unknown (in remission) (n=1), dementia (n=1). In 70-80y, IDI>80% had significantly improved PFS, DFS and OS. In ≥80y, there was no difference in PFS, DFS or OS according to IDI 80% (Fig A-F). UVA Univariable predictors of worse PFS and OS included age*, ECOG PS*, DOX IDI*, CYCLO IDI*, combined IDI*, IPI 3-5, aaIPI 2-3, raised LDH, male gender and B symptoms (all p MVA IDI* remained an independent predictor of PFS, DFS and OS. Using 70-80y IDI>80 (HR 1.0) as the comparator, the following were associated with significantly increased risk of PD and / or death in PFS and OS in MVA: 70-80y IDI80. Compared to 70-80y IDI>80 (HR 1.00), the HR for DFS in ≥80y IDI>80 approached significance (p = 0.07) vs PFS and OS, suggesting that causes other than PD account in part for inferior OS and PFS (Table 1). Conclusions To our knowledge, this is the largest series that has systematically analysed RDI, IDI (DOX, CYCLO and combination) and co-morbidities in consecutive unselected DLBCL ≥70y. Consistent with recent literature (Juul et al, 2018), there is no clear benefit to PFS, DFS or OS in dose intensifying (IDI>80) in ≥80y. IDI is a clear independent predictor of outcome across all pts. Pts 70-80y with IDI Disclosures Eyre: Janssen: Consultancy, Other: travel support; Roche: Consultancy; Abbvie: Consultancy, Other: travel support; Gilead: Consultancy, Other: travel support; Celgene: Other: travel support. Fox:Celgene: Consultancy, Other: Travel, Speakers Bureau; Sunesis: Consultancy; Abbvie: Consultancy, Other: Travel, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel, Speakers Bureau; Gilead: Consultancy, Other: Travel, Research Funding, Speakers Bureau; Roche: Consultancy, Other: Travel, Research Funding, Speakers Bureau. McMillan:Celgene: Honoraria, Other: travel support; BMS: Honoraria; Amgen: Honoraria; Takeda: Other: travel support; Roche: Consultancy, Honoraria, Other: travel support; Pfizer: Research Funding; MSD: Honoraria. Bishton:Abbvie: Research Funding; Roche: Research Funding; Takeda: Other: travel support to ASH; Gilead: Research Funding. Collins:Celleron: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Celgene Corporation: Research Funding; MSD: Consultancy, Honoraria; Amgen: Research Funding; Pfizer: Consultancy, Honoraria.

We present a case of a 38-year-old woman who presented with symptoms suggestive of intra-abdominal or pelvic malignancy: marked weight loss, abdominal pain, altered bowel habit, anorexia and fatigue. The findings of multiple peritoneal deposits, adnexal and presacral masses on CT imaging and appearances on diagnostic laparotomy also suggested malignancy. However, the histological analysis was inconsistent with malignancy and revealed an infection with Actinomyces israelii. The patient started a course of intravenous antibiotics and complete resolution is expected. An intrauterine contraceptive device was identified as the likely source of the infection.

This tattoo belongs to a builder recently diagnosed with peripheral T-cell lymphoma. Six days after autologous bone marrow transplantation, while neutropaenic, the patient developed fever of unknown origin. During this period three of his tattoos, all inked before …