An international analysis evaluating frontline bendamustine with rituximab in extranodal marginal zone lymphoma

: Extranodal marginal zone lymphoma (EMZL) is a heterogeneous non-Hodgkin lymphoma. No consensus exists regarding the standard-of-care in patients with advanced-stage disease. Current recommendations are largely adapted from follicular lymphoma, for which bendamustine with rituximab (BR) is an established approach. We analyzed the safety and efficacy of frontline BR in EMZL using a large international consortium. We included 237 patients with a median age of 63 years (range, 21-85). Most patients presented with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (n = 228; 96.2%), stage III/IV (n = 179; 75.5%), and intermediate (49.8%) or high (33.3%) Mucosa Associated Lymphoid Tissue International Prognosis Index (MALT-IPI). Patients received a median of 6 (range, 1-8) cycles of BR, and 20.3% (n = 48) received rituximab maintenance. Thirteen percent experienced infectious complications during BR therapy; herpes zoster (4%) was the most common. Overall response rate was 93.2% with 81% complete responses. Estimated 5-year progression-free survival (PFS) and overall survival (OS) were 80.5% (95% CI, 73.1% to 86%) and 89.6% (95% CI, 83.1% to 93.6%), respectively. MALT-IPI failed to predict outcomes. In the multivariable model, the presence of B symptoms was associated with shorter PFS. Rituximab maintenance was associated with longer PFS (hazard ratio = 0.16; 95% CI, 0.04-0.71; P = .016) but did not impact OS. BR is a highly effective upfront regimen in EMZL, providing durable remissions and overcoming known adverse prognosis factors. This regimen is associated with occurrence of herpes zoster; thus, prophylactic treatment may be considered

Prevalence and correlates of current cigarette smoking among transgender women in Argentina

Fil: Cartujano-Barrera, F. Department of Public Health Sciences, University of Rochester Medical Center; Rochester, NY. United StatesFil: Mejia, RM. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Mejia, RM. Department of Ambulatory Care, Universidad de Buenos Aires; Buenos Aires. ArgentinaFil: Mejia, RM. CEDES. Centro de Estudios de Estado y Sociedad. Área de Salud, Economía y Sociedad; Buenos Aires. ArgentinaFil: Radusky, PD. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Cardozo, Nadir. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Cardozo, Nadir. Asociación de Travestis, Transexuales y Transgéneros de Argentina; Buenos Aires. ArgentinaFil: Duarte, M. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Duarte, M. Casa Trans; Buenos Aires. ArgentinaFil: Fabian, S. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Fabian, S. Hotel Gondolín; Buenos Aires. ArgentinaFil: Caballero, R. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Zalazar, V. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Ramos-Pibernus, A. School of Behavioral and Brain Sciences, Ponce Health Sciences University; Ponce, PR. United StatesFil: Alpert, AB. Department of Public Health Sciences, University of Rochester Medical Center; Rochester, NY. United StatesFil: Alpert, AB. Division of Hematology, Department of Medicine, Yale School of Medicine; New Haven, CT. United StatesFil: Cupertino, AP. Department of Public Health Sciences, University of Rochester Medical Center; Rochester, NY. United StatesFil: Cupertino, AP. Department of Surgery, University of Rochester Medical Center; Rochester, NY. United StatesFil: Frola, C. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaFil: Aristegui, I. Division of Implementation Research, Fundación Huésped; Buenos Aires. ArgentinaObjective: To assess the prevalence of current cigarette smoking among transgender women in Argentina, and to examine the unique associations of current cigarette smoking with demographic and psychosocial factors. Methods: This study is a secondary data analysis of the TransCITAR – a prospective cohort study of transgender individuals living in Buenos Aires, Argentina – baseline data. The baseline survey collected information on sociodemographic characteristics, perceived health status, depressive symptoms, suicide attempts, current cigarette smoking, alcohol use disorder, and substance use. Participants were also asked about lifetime experiences of physical and sexual violence perpetrated by partners, clients and/or the police, and experiences of gender identity stigma in the past year from healthcare workers and the police. Lastly, participants were asked if they had ever been arrested. Fisher’s exact test was used to compare proportions in categorical variables and student t-test was used for continuous variables. Significant associations with current cigarette smoking were tested in a logistic regression model adjusted for all significant associations. Results: A total of 41.7% of participants (n = 393) reported current cigarette smoking. Compared to their non-smoking counterparts, participants who reported current cigarette smoking (1) had completed less education, (2) were more likely to be born in Argentina, (3) more likely to had migrated to Buenos Aires from other parts of the country, (4) more likely to report a history of sex work, (5) more likely to perceive their health as excellent, (6) more likely to screen positive for hazardous alcohol drinking, (7) more likely to report any substance and cocaine use in the past year, (8) more likely to experience gender identity stigma from the police in the past year, and (9) more likely to being arrested in their lifetime (all p’s < 0.05). After controlling for all significant associations, education level of less than high school (AOR = 1.79, 95% CI 1.02–2.12), hazardous drinking (AOR = 2.65, 95% CI 1.30–5.37), and any substance use in the last year (AOR = 2.14, 95% CI 1.16–3.94) were positively and independently associated with current cigarette smoking. Conclusion: Among transgender women in Argentina, current cigarette smoking was more than double the rate for cisgender women. Current cigarette smoking was associated with education, hazardous drinking, and any drug use. These results will inform future smoking cessation interventions among transgender women in Argentina

Frontline Bendamustine and Rituximab in Extranodal Marginal Zone Lymphoma: An International Analysis

Introduction: There is no standard induction therapy in extranodal marginal zone lymphoma (EMZL); current guidelines borrow from follicular lymphoma, where bendamustine and rituximab (BR) is an accepted standard. The data on BR in EMZL is limited (Rummel MJ et al. Lancet 2013 & Salar A et al. Blood 2017), so we explored BR activity as part of an international consortium. Methods: This retrospective analysis involved 11 cancer centers from US and Italy. We included patients with EMZL treated with frontline BR (1/2008 to 12/2019). Expert pathology review was performed by each participating institution following the 2016 WHO classification. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier and associations with prognostic factors were assessed by log-rank test, univariable (UVA) and multivariable (MVA) Cox regression. MVA Cox models were constructed by selecting variables significant univariately. Results: 136 patients were identified; however, 18 patients with EMZL only located in bone marrow (BM) were excluded from this analysis to prevent possible inclusion of lymphoplasmacytic lymphoma. Thus, 118 patients were included in this study. Patient characteristics comprised median age of 61.5 years (range 21 to 85 years), women: 56.8%, ECOG performance status 0-1: 86%, stage III-IV: 79.7%, no B symptoms: 81.4%, normal LDH: 75.4%, BM involvement: 25.4%, and MALT-IPI score < 2: 63.6%. Most common extranodal (EN) sites were lung (22%), gastric (13.6%), ocular (11%), soft tissue (10.2%), salivary gland (10%), and gastrointestinal non-gastric (7.6%). Most patients presented with 1 or 2 EN sites (48.3% and 30.5%, respectively). Majority of patients (83.9%) had < 4 nodal sites. Paraprotein was positive in 27 of 80 (33.7%) patients with majority harboring IgM. The median number of BR cycles was 6 (range 1 to 6). Consolidation with radiation therapy was performed in 6% of the patients. Treatment response was determined by PET/CT in 70% and CT scans in the rest. The response to treatment was as follows: CR: 96 (81.4%), PR: 13 (11%), SD: 2 (1.7%), PD: 4 (3.4%), and unknown: 3 (2.5%) patients. No differences in response rate were observed by EN location. The incidence of infectious complications was 14% including herpes zoster (25%), pneumonia (18.7%) and influenza (18.7%). No treatment-related mortality was observed. Rituximab maintenance was implemented in 17% (n= 20) of the patients for a median duration of 11 (range 1 to 46) months. Biopsy-proven transformation to diffuse large B cell lymphoma occurred in 5.9% of the patients. Patients with lymphoma transformation had a higher mean SUV on diagnostic PET/CT (13.48 vs 7.77, P= 0.037, respectively). Secondary malignancies were observed in 6% of the patients with 1 case of acute myeloid leukemia. With a median follow up of 2.85 (range 0.08 to 9.45) years, the estimated 5-years PFS (Figure 1) and OS (Figure 2) were 72.3% (95%CI 59.3-81.8%) and 85.6% (95%CI 75.0-92.0%), respectively. No survival difference was observed between patients achieving CR or PR followed or not by rituximab maintenance, but the number of patients receiving maintenance was small. Similarly, no survival differences were observed in patients with gastric EMZL compared to non-gastric locations or by MALT-IPI score risk category. In both UVA and MVA analyses, variables associated with shorter survival were ECOG performance status ≥2 and failure to achieve CR (for MVA: ECOG PS ≥ 2 (HR: 6.56, P=0.006) and failure to achieve CR (HR: 5.35 P<0.001)). The implementation of rituximab maintenance was not associated with lower risk for an event in patients achieving CR and PR (MVA HR: 0.29, P=0.146). Conclusion: This study represents the largest analysis to date evaluating the activity and safety of BR in untreated EMZL. BR is a highly effective platform in upfront treatment of EMZL with majority of the patients achieving complete and durable remissions. ECOG PS ≥ 2 and failure to achieve CR were identified as prognostic factors associated with worse outcome in BR treated patients. High incidence of herpes zoster infection was observed in this study which has not been previously reported. In addition, increased median PFS and lower incidence of infectious complications was observed in this study compared to prior reports. Disclosures Alderuccio: ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Inovio Pharmaceuticals: Other: Family member; Forma Therapeutics: Other: Family member; Agios Pharmaceuticals: Other: Family member; Oncinfo: Honoraria; OncLive: Honoraria; Puma Biotechnology: Other: Family member; Foundation Medicine: Other: Family member. Beaven:Tessa Therapeutics: Research Funding; Seattle Genetics: Research Funding; Celgene: Research Funding; LoxoOncology: Research Funding; MorphoSysAb: Research Funding; Roche: Research Funding. Shouse:Kite Pharma: Honoraria, Speakers Bureau. Epperla:Verastem Oncology: Speakers Bureau; Pharmacyclics: Honoraria. Castillo:TG Therapeutics: Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Kymera: Consultancy; Abbvie: Research Funding; Janssen: Consultancy, Research Funding. Voorhees:AstraZeneca: Research Funding. Martin:Regeneron: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy, Research Funding; Teneobio: Consultancy; Sandoz: Consultancy; I-MAB: Consultancy; Bayer: Consultancy; Beigene: Consultancy; Cellectar: Consultancy; Incyte: Consultancy; Kite: Consultancy; Morphosys: Consultancy. Kamdar:Roche: Research Funding. Herrera:AstraZeneca: Research Funding; Karyopharm: Consultancy; Immune Design: Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Pharmacyclics: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Merck: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding. Friedberg:Roche: Other: Travel expenses; Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Portola Pharmaceuticals: Consultancy; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy; Astellas: Consultancy; Seattle Genetics: Research Funding. Zinzani:Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lossos:Seattle Genetics: Consultancy, Other; Stanford University: Patents & Royalties; Janssen Scientific: Consultancy, Other; Verastem: Consultancy, Honoraria; Janssen Biotech: Honoraria; NCI: Research Funding