ALBERT

Description: Introduction: Anthracyclines are cytotoxic antibiotics used in the treatment of lymphomas. Myocardiopathy is a well-known toxicity of anthracyclines, and both acute/subacute and late-onset presentations have been described. Early detection of asymptomatic cardiac dysfunction and identification of biomarkers for anthracycline cardiotoxicity risk may be important to prevent irreversible heart damage. Objective: To prospectively evaluate the incidence, time of appearance and clinico-biological variables associated with the development of myocardiotoxicity in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP/R-CHOP-like regimens. Patients and Methods: one hundred and sixty six patients with DLBCL from 05/2004 to 05/2014. Excluded: HIV infection (10), treatment without anthracyclines (21) and other causes (5) (Table 1). Left ventricular ejection fraction (LVEF) determined by high resolution echocardiography and the N-terminal brain natriuretic peptide (NT-proBNP) fragment were done prior initiation of treatment, at the end and every 6-12 months thereafter. Myocardiotoxicity was defined as: LVEF 15% if prior LVEF 600 +/- FRESCO 〉4.5 (Figure 1). Finally, we performed a computational modeling using 12 Bayesian networks to analyze the connections between demographic characteristics, cardiovascular risk factors, treatment, occurrence of cardiotoxicity and death (Figure 2 illustrates one of the networks). Conclusions: myocardiotoxicity induced by anthracyclines remains an important problem in the daily practice. The FRESCO cardiovascular risk function is useful for predictingmyocardiotoxicity and levels of NT-proBNP improved accuracy myocardiotoxicity risk. We propose that patients with NT-proBNP 〉600 pg/mL or FRESCO 〉 4.5 should have a specific cardiologic surveillance and follow-up in cardio-oncology units from the start of their anthracyclin-containing chemotherapy. Disclosures No relevant conflicts of interest to declare.

Description: INTRODUCTION Chemotherapy-induced hepatitis B virus (HBV) reactivation is a well-recognized complication and is a potentially life-threatening condition in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg]-positive). Rituximab has been associated with an increase in HBV reactivation in chronic HBV patients (45%) and even in patients with resolved infection (HBsAg negative and hepatitis B core antibody [anti-HBc]-positive (22%); however, the reported frequency varies among different studies. Current guidelines for management of chronic HBV recommend routine antiviral HBV prophylaxis with lymphoma before starting chemotherapy. In contrast, there is little evidence-based consensus regarding patients with resolved HBV infection. Aim: To analyze the incidence of HBV reactivation and the role of antiviral HBV prophylaxis in lymphoma patients with chronic HBV or resolved HBV treated with chemotherapy, immunotherapy or immunochemotherapy managed according to our institutional HBV guidelines. Secondary endpoints were to analyze the incidence of HBV in this population and HBV guidelines adherence. PATIENTS AND METHODS Lymphoma patients with chronic HBV or resolved HBV in a single center. HBV viral status definitions: Active Chronic HBV infection: HBsAg positive, anti-HBc positive and HBV DNA 〉2000 IU/mL; Inactive Carriers: HBsAg positive, Anti-HBc positive, HBV DNA undetectable or

Description: Introduction The use of maintenance treatment with rituximab in B lymphomas has improved the results in terms of progression free survival in follicular lymphoma (PRIMA trial). This improvement has been seen in other types of indolent lymphomas including chronic lymphatic leukemia or specific cases of aggressive lymphomas with or without low grade associated component. However, the rituximab maintenance, even though is a well-tolerated strategy, is not free of toxicity. Our objective is reporting the rituximab toxicity associated to the maintenance with rituximab in a series of B-cell lymphomas treated with immunochemotherapy in first line in Hospital Son Espases (HUSE) and Hospital del Mar (HM). Methods and materials To avoid selection bias, we retrospectively identified from the Pharmacy registries of HUSE and HM those patients who had been treated with rituximab maintenance between 2002 and 2014 in first line of induction treatment with conventional immunotherapy or immunochemotherapy. Second lines or more intensive treatments were excluded. We obtained information about diagnosis, prognostic and outcome in all the patients, including levels of immunoglobulins as well as the seriousness of infections or other related side effects. Polymorphisms FcgRIIIa were analyzed using RT-PCR and sequencing. Results With the previous criteria 82 patients were included. Table 1 shows the diagnostic characteristics and the treatment of the patients. The median of age was 65 years; most cases were follicular lymphoma treated with R-CHOP or R-B and receiving maintenance with rituximab every 2 months (66%). Table 2 describes toxicity related to rituximab maintenance: hypogammaglobulinaemia IgG, IgA or both in the 27%, 21% and 11% of the cases respectively. When we analyzed the role of polymorphisms of FcgRIIIa we found that the patients with homozigous polymorphism VV were exempt of hypogammaglobulinaemia IgG or IgA. Moreover the polymorphism FF was associated meaningfully with a greater incidence of hypogammaglobulinaemia IgA (p=0.022). Only the 8% of the cases of hypogammaglobulinaemia needed treatment with intravenous immunoglobulins and only 6% had grade 3-4 infections. 21% of the patients treated with rituximab maintenance developed grade 3-4 neutropenia, generally reversible with the administration of G-CSF and without serious infections. Increase of mortality was not observed related with the presence of hypogamaglobulinaemia IgG (p=0.34), IgA (p=0.59) or both (p=0.59) or grade 3-4 neutropenia secondary to rituximab (p=0.38). Conclusions Between one-quarter or one-fifth of the patients who received maintenance therapy with rituximab during 2 years associate hypogammaglobulinaemia IgG, IgA and/or neutropenia as toxicity. Nevertheless these complications are generally mild, without related severe infections or increase of mortality. Table 1. Clinical characteristics of the series Median of age 65 (27-85) Sex 41 (50%) / 41 (50%) ECOG PS 〉1 7 (9%) Type of lymphoma:- Folicular lymphoma- DLBCL- CLL/SLL- Marginal lymphoma- Mantel cell lymphoma- Other 46 (56%)13 (16%)8 (10%)6 (7%)5 (6%)4 (5%) Stage III-IV 71 (87%) B symptoms 29 (35%) Induction treatment:- R-CHOP/R-CVP- R-B- Rituximab alone- Schema with Fludarabine-R- Intensive schemas- Others 50 (61%)13 (16%)9 (11%)4 (5%)3 (4%)3 (4%) Type of maintenance (2 years):- Every 2 months- Every 3 months- Every 6 months (4 weeks) 54 (66%)15 (18%)1 3 (16%) Table 2. Rituximab maintenance attributable toxicity Polimorphism FcgRIIIA Type of toxicity Total FF FV VV p Hypogammaglobulinaemia- IgG- IgA- Double IgG + IgA 22 (27%)17 (21%)9 (11%) 7 (23%)11 (37%)3 (10%) 15 (31%)6 (12%)6 (12%) 0 (0%)0 (0%)0 (0%) 0.340.0220.74 Treatment with immunoglobulins iv 7 (8%) 3 (10%) 4 (8%) 0 (0%) 0.79 Grade 3-4 infections: 5 (6%) 2 (7%) 3 (6%) 0 (0%) 0.87 Grade 3-4 neutropenia: 17 (21%) 8 (27%) 8 (17%) 1 (25%) 0.59 Disclosures No relevant conflicts of interest to declare.

Description: Introduction: DLBCL is the more common non Hodgkin lymphoma. This is an aggressive lymphoma that is treated with a standard chemotherapy regimen: R-CHOP. In the last years attempts have been done to improve the outcome both increasing dose-density (CHOP14) or intensity (CHOEP, ACVBP, autologous stem cell transplantation) without obtaining benefit in terms of survival. This has allowed setting R-CHOP administered every 21 days (R-CHOP21) as the standard treatment for DLBCL patients. RDI is an important issue to consider when treating malignancies. Although this a well-known prognostic factor in Hodgkin lymphoma, scarce information has been published in DLBCL. Objective: The purpose of this study is further analyzing the prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14, to evaluate its differential impact when increasing dose density. Material and methods: All patients diagnosed of DLBCL from January-1999 to June-2013 at University Hospital Son Espases were retrospectively identified from Pathology Department registry to avoid selection bias. Only patients treated with R-CHOP21 or R-CHOP14 +/- radiotherapy were included (N=115). To increase the R-CHOP14 cohort we added also all patients treated with R-CHOP14 in the same time period in two additional hospitals (Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona) identified from their Pharmacy registries to avoid selection bias (N=42). Other regimes, consolidations or maintenance were excluded. Table 1 shows main characteristics of the global series (N=157). RDI represents the ratio of the amount of a drug actually administered to the amount planned for a fixed time period. RDI was calculated as previously described. Briefly, RDI of each drug was obtained followed by an average of RDI in CHOP consisting in the sume of RDI of the 3 drugs divided by 3. Main prognostic factors at diagnosis in DLBCL were obtained, including international prognostic index (IPI) factors. Evaluations were carried out following standard guidelines. Results: Overall response and complete response rates were similar in both groups:86% and 76% for R-CHOP21 and 94% and 74% for R-CHOP14(p=0.17 and p=0.85, respectively). Median follow-up for alive patients was 68 months (4-156). There were no differences between the two cohorts in terms of either OS or PFS (Figure 1). In the R-CHOP21, both a reduction higher than 15% in RDI [RR 7.41 (2.51-21.83); (p 1 17 (23%) 18 (22%) 0.85 Ann Arbor stage III-IV 40 (54%) 48 (58%) 0.75 B-symptoms 25 (34%) 26 (31%) 0.86 Elevated LDH 33 (46%) 40 (49%) 0.75 〉 1 extranodal site 8 (11%) 19 (23%) 0.057 Bulky disease 23 (31%) 34 (41%) 0.24 R-IPI unfavorable 24 (32%) 26 (32%) 1 NCCN-IPI: - Low - Low-intermediate - High-intermediate - High 9 (13%) 27 (39%) 26 (38%) 7 (10%) 17 (21%) 35 (44%) 24 (30%) 4 (5%) 0.31 Elevated Beta-2-microglobulin 32 (49%) 31 (39%) 0.24 Radiotherapy 27 (36%) 27 (32%) 0.62 Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.