Immunochemotherapy and Maintenance With Obinutuzumab or Rituximab in Patients With Previously Untreated Marginal Zone Lymphoma in the Randomized GALLIUM Trial

The aim of this study was to explore the efficacy and safety of obinutuzumab (G)- versus rituximab (R)-chemotherapy in a subgroup of patients with previously untreated marginal zone lymphoma (MZL) in the phase III GALLIUM trial (NCT01332968). Patients had stage III/IV (or stage II with bulky disease), splenic, nodal, or extranodal MZL requiring treatment. Patients were randomized 1:1 to receive G- or R-chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; cyclophosphamide, vincristine, and prednisone; or bendamustine, allocated at patient level). Patients with complete/partial response at the end of induction (EOI) received G/R maintenance. Investigator-assessed progression-free survival (PFS), other time-to-event endpoints, response, and safety were assessed. Overall, 195 patients with MZL were included in this analysis: G-chemotherapy (n = 99), R-chemotherapy (n = 96). Median observation time: 59.3 months. No meaningful difference was observed between arms for PFS (4-y PFS rates: G-chemotherapy, 72.6%; R-chemotherapy, 64.1%), other time-to-event endpoints, or EOI response rates (by computed tomography [CT; G-chemotherapy, 81.8%; R-chemotherapy, 81.3%] and positron emission tomography CT [G-chemotherapy, 79.2%; R-chemotherapy, 87.5%]). All patients experienced ≥1 adverse event (AE). G-chemotherapy was associated with a higher incidence of grade 3–5 (86.1% versus 77.4%), grade 5 (14.9% versus 9.7%), and serious (66.3% versus 51.6%) AEs versus R-chemotherapy. Both arms had a higher incidence of grade 3–5 and serious AEs than patients with follicular lymphoma (GALLIUM), with G-chemotherapy being less tolerable than R-chemotherapy. Based on the observed tolerability of G-chemotherapy versus R-chemotherapy, and the comparable efficacy of G-chemotherapy and R-chemotherapy in this analysis, G-chemotherapy cannot be recommended as first-line treatment for MZL

Multi-omic analysis of the tumor microenvironment shows clinical correlations in Ph1 study of atezolizumab +/- SoC in MM

Multiple myeloma (MM) remains incurable, and treatment of relapsed/refractory (R/R) disease is challenging. There is an unmet need for more targeted therapies in this setting; deep cellular and molecular phenotyping of the tumor and microenvironment in MM could help guide such therapies. This phase 1b study (NCT02431208) evaluated the safety and efficacy of the anti-programmed death-ligand 1 monoclonal antibody atezolizumab (Atezo) alone or in combination with the standard of care (SoC) treatments lenalidomide (Len) or pomalidomide (Pom) and/or daratumumab (Dara) in patients with R/R MM. Study endpoints included incidence of adverse events (AEs) and overall response rate (ORR). A novel unsupervised integrative multi-omic analysis was performed using RNA sequencing, mass cytometry immunophenotyping, and proteomic profiling of baseline and on-treatment bone marrow samples from patients receiving Atezo monotherapy or Atezo+Dara. A similarity network fusion (SNF) algorithm was applied to preprocessed data. Eighty-five patients were enrolled. Treatment-emergent deaths occurred in 2 patients; both deaths were considered unrelated to study treatment. ORRs ranged from 11.1% (Atezo+Len cohorts, n=18) to 83.3% (Atezo+Dara+Pom cohort, n=6). High-dimensional multi-omic profiling of the tumor microenvironment and integrative SNF analysis revealed novel correlations between cellular and molecular features of the tumor and immune microenvironment, patient selection criteria, and clinical outcome. Atezo monotherapy and SoC combinations were safe in this patient population and demonstrated some evidence of clinical efficacy. Integrative analysis of high dimensional genomics and immune data identified novel clinical correlations that may inform patient selection criteria and outcome assessment in future immunotherapy studies for myeloma

Baseline total metabolic tumor volume is prognostic for refractoriness to Iimunochemotherapy in DLBCL: results from GOYA

Introduction A good response to initial therapy is key to maximizing survival in patients with diffuse large B-cell lymphoma (DLBCL), but patients with chemorefractory disease and early progression have poor outcomes. Patients and Methods Data from the GOYA study in patients with DLBCL who received first-line rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) were analyzed. Positron emission tomography/computed tomography (PET/CT)-derived characteristics associated with total metabolic tumor volume (TMTV) and clinical risk factors for primary chemorefractory disease and disease progression within 12 months (POD12) were explored. Results Of those patients fulfilling the criteria for analysis, 108/1126 (10%) were primary chemorefractory and 147/1106 (13%) had POD12. Primary chemorefractory and POD12 status were strongly associated with reduced overall survival. After multivariable analysis of clinical and imaging-based risk factors by backward elimination, only very high TMTV (quartile [Q] 1 vs. Q4 odds ratio [OR]: 0.45; P = .006) and serum albumin levels (low vs. normal OR of 1.86; P = .004) were associated with primary chemorefractoriness. After additionally accounting for BCL2/MYC translocation in a subset of patients, TMTV and BCL2/MYC double-hit status remained as significant predictors of primary chemorefractoriness (Q1 vs. Q4 OR: 0.32, P = .01 and double-hit vs. no-hit OR of 4.47, P = .02, respectively). Risk factors including very high TMTV, high sum of the product of the longest diameters (SPD), geographic region (Asia), short time since diagnosis, extranodal involvement and low serum albumin were retained for POD12. Conclusion PET-derived TMTV has prognostic value in identifying patients at risk of early treatment failure

Immunolymphoscintigraphy for Metastatic Sentinel Nodes: Test of a Model

Aim. To develop a method and obtain proof-of-principle for immunolymphoscintigraphy for identification of metastatic sentinel nodes. Methods. We selected one of four tumour-specific antibodies against human breast cancer and investigated (1), in immune-deficient (nude) mice with xenograft human breast cancer expressing the antigen if specific binding of the intratumorally injected, radioactively labelled, monoclonal antibody could be scintigraphically visualized, and (2) transportation to and retention in regional lymph nodes of the radioactively labelled antibody after subcutaneous injection in healthy rabbits. Results and Conclusion. Our paper suggests the theoretical possibility of a model of dual isotope immuno-lymphoscintigraphy for noninvasive, preoperative, malignant sentinel node imaging

A prognostic model integrating PET-derived metrics and image texture analyses with clinical risk factors from GOYA

Image texture analysis (radiomics) uses radiographic images to quantify characteristics that may identify tumour heterogeneity and associated patient outcomes. Using fluoro‐deoxy‐glucose positron emission tomography/computed tomography (FDG‐PET/CT)‐derived data, including quantitative metrics, image texture analysis and other clinical risk factors, we aimed to develop a prognostic model that predicts survival in patients with previously untreated diffuse large B‐cell lymphoma (DLBCL) from GOYA (NCT01287741). Image texture features and clinical risk factors were combined into a random forest model and compared with the international prognostic index (IPI) for DLBCL based on progression‐free survival (PFS) and overall survival (OS) predictions. Baseline FDG‐PET scans were available for 1263 patients, 832 patients of these were cell‐of‐origin (COO)‐evaluable. Patients were stratified by IPI or radiomics features plus clinical risk factors into low‐, intermediate‐ and high‐risk groups. The random forest model with COO subgroups identified a clearer high‐risk population (45% 2‐year PFS [95% confidence interval (CI) 40%–52%]; 65% 2‐year OS [95% CI 59%–71%]) than the IPI (58% 2‐year PFS [95% CI 50%–67%]; 69% 2‐year OS [95% CI 62%–77%]). This study confirms that standard clinical risk factors can be combined with PET‐derived image texture features to provide an improved prognostic model predicting survival in untreated DLBCL

The association between exposure to social media alcohol marketing and youth alcohol use behaviors in India and Australia

© 2018 The Author(s). Background: Alcohol marketing on social networking sites (SNS) is associated with alcohol use among young people. Alcohol companies adapt their online marketing content to specific national contexts and responses to such content differ by national settings. However, there exists very little academic work comparing the association between alcohol marketing on SNS and alcohol use among young people in different national settings and across different SNS. Therefore, we aimed to extend the limited existing work by investigating and comparing the association between self-reported exposure to alcohol marketing on three leading SNS (Facebook, YouTube, and Twitter) and alcohol use among young people in diverse national contexts (India and Australia). Methods: Cross-sectional, self-report data were obtained from a convenience sample of 631 respondents (330 in India; 301 in Australia) aged 13-25 years via online surveys. Respondents answered questions on their drinking behaviors and involvement with alcohol marketing on SNS. Results: Many respondents from both countries reported interacting with alcohol content online, predominantly on Facebook, followed by YouTube and then Twitter. The interaction was primarily in the forms of posting/liking/sharing/commenting on items posted on alcohol companies' social media accounts, viewing the event page/attending the event advertised by an alcohol company via social media, and/or accessing an alcohol website. Multivariate analyses demonstrated significant associations between respondents' interaction with alcohol content and drinking levels, with effects differing by SNS, demographic group, and country. For example, having friends who shared alcohol-related content was an important predictor of usual alcohol consumption for Indian respondents (p <.001), whereas posting alcohol-related information themselves was a stronger predictor among Australians (p <.001). Conclusions: The results suggest that interaction with alcohol-related content on SNS is associated with young people's alcohol use behaviors and that these behaviors vary by national settings. This study extends previous work by demonstrating this connection across varying social media platforms and national contexts. The results highlight the need to formulate and implement strategies to effectively regulate the SNS alcohol marketing, especially among younger SNS users