scholarly journals Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Harrysson ◽  
Sandra Eloranta ◽  
Sara Ekberg ◽  
Gunilla Enblad ◽  
Mats Jerkeman ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Refractory Disease ◽  
Curative Intent ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

AbstractWe performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007–2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7–66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7–24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5–3.6, n = 118) overall, and 8.0% (95% CI: 6.0–10.6, n = 48) among patients with high CNS-IPI (4–6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.

scholarly journals Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 498-505 ◽  
Author(s):  
Jonathan W. Friedberg
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Clinical Approach ◽  
Refractory Disease ◽  
Curative Intent ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Despite overall improvements in outcomes of diffuse large B-cell lymphoma (DLBCL), approximately one-third of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality. Novel insights from gene-expression analyses have increased our understanding of chemotherapy resistance and yielded rational targets for therapeutic intervention to both prevent and treat relapsed/refractory DLBCL. The clinical approach to relapsed/refractory DLBCL should include high-dose therapy and autologous stem cell transplantation (HD-ASCT) with curative intent in patients without comorbidities. Results from the recently reported CORAL study suggest that patients refractory to rituximab-containing regimens have inferior outcomes with HD-ASCT. Ongoing efforts to improve ASCT include novel conditioning regimens and evaluation of maintenance approaches after ASCT. Unfortunately, because the majority of patients are not eligible for ASCT due to refractory disease or age/comorbidities, these approaches have limited impact. The large group of patients not eligible for ASCT have incurable disease and should be referred for clinical trials of rationally targeted agents.

Outcome of primary mediastinal large B-cell lymphoma using R-CHOP: impact of a PET-adapted approach

Blood ◽  
2020 ◽  
Vol 136 (24) ◽  
pp. 2803-2811
Author(s):  
Anna R. Hayden ◽  
Petter Tonseth ◽  
Derrick G. Lee ◽  
Diego Villa ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pet Scan ◽  
Primary Therapy ◽  
Refractory Disease ◽  
Curative Intent ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

scholarly journals Incidence and Outcome of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in a Population-Based Cohort of 3165 Patients in Sweden

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2975-2975 ◽  
Author(s):  
Sara Harrysson ◽  
Sandra Eloranta ◽  
Sara Ekberg ◽  
Gunilla Enblad ◽  
Mats Jerkeman ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Late Relapse ◽  
Refractory Disease ◽  
Curative Intent ◽  
Early Relapse ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background Our knowledge around the incidence of relapse and primary refractory disease in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era is mostly derived from randomized controlled trials or specialized center cohorts presenting selected patient materials. With new therapies being evaluated and launched at diagnosis as well as in the relapsed/refractory setting there is a need for a better understanding of the response and outcome with current treatment strategies. Here we investigated the incidence of primary refractory DLBCL and first relapse as well as survival among patients with relapsed/refractory DLBCL in a population-based cohort. Methods Patients with a primary diagnosis of DLBCL in 2007-2014 were identified using the Swedish Lymphoma Register in 5 of 6 health care regions, and followed until October 31st 2017. Primary CNS lymphomas and primary mediastinal B-cell lymphomas were excluded. The register contains information about clinical characteristics, primary treatment, treatment response and relapse. Information regarding treatment response and progression/relapse was validated through medical chart review in all patients. Primary treatment with curative intent was defined as having started treatment with anthracycline-based chemotherapy (mostly R-CHOP). Early relapse was defined as having primary refractory disease (stable or progressive disease (SD/PD) at response evaluation) or relapse within a year from diagnosis. Overall and progression-free survival probabilities were estimated with the Kaplan-Meier method in the entire cohort and among relapsed/refractory patients by early/late relapse and by age +/- 70 years. Additionally, cumulative incidence of relapsed/refractory disease by follow-up time was shown graphically accounting for the presence of competing risks. Results In the study population of 3165 patients, median age at diagnosis was 71 years (range 18 to 97). In this unselected cohort, 80% of the patients started treatment with curative intent. Five-year overall survival (OS) for patients treated with curative intent was 78% (95% CI: 76-80) and 5-year progression free survival (PFS) was 60% (95% CI: 58-62). Patients who received non-curative intent or palliative therapy (20%) had a median OS of 4.7 months (95% CI: 3.4-5.7). The 10-year cumulative incidence of relapsed/refractory disease in patients treated with curative intent was 22% (95% CI: 20-24) and the majority relapsed within two years (n=315, 60%). Five percent of the patients starting primary treatment with curative intent, only received 1 or 2 treatment cycles and were not evaluated for response. Patients with relapsed/refractory disease had a poor prognosis. For patients with early relapse, median survival from the date of relapse was 4.6 months (95% CI: 4.1-5.7) and 5-year OS was 11% (95% CI; 8-15) whereas patients with late relapse had a median survival of 18.0 months (95% CI: 13.0-24.5) and a 5-year OS of 26% (95% CI: 20-33). Survival in younger patients (≤70 years) by early and late relapse was higher although still low; 5-year OS in early relapse was 17% (95% CI: 12-23) and in late relapse 37% (95% CI: 27-48). Among older patients (>70 years) with early relapse, 5-year OS was only 4% (95% CI: 2-9) and in patients with late relapse it was 16% (95% CI: 9-24). More information regarding treatment intensity among relapsed/refractory patients will be presented. Conclusion The 10-year cumulative incidence of relapsed/refractory disease in patients with DLBCL treated with curative intent is 22% in this population-based study, which is lower compared to previous reports. Outcome for patients with relapsed/refractory disease continues to be poor especially for patients with early progression/relapse, even among younger patients going on to intensive second-line chemotherapy aiming for autologous stem cell transplantation. These results underscore both the urgency of new therapies for relapsed/refractory DLBCL as well as the need for identification of high-risk patients already at diagnosis. Figure 1. Overall survival (OS) and progression-free survival (PFS) among 3165 patients with diffuse large B-cell lymphoma (DLBCL) diagnosed in Sweden 2007-2014 treated with curative or palliative intent, and cumulative incidence of relapsed/refractory disease and survival among 529 relapsed/refractory patients by timing of relapse (early/late) and age (+/-70 years). Figure. Figure. Disclosures Harrysson: Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals. Eloranta:Janssen Pharmaceuticals: Other: S Eloranta is currently employed as a project coordinator and her salary is funded via a public-private real world evidence collaboration between Karolinska Institutet and Janssen Pharmaceuticals. Ekberg:Janssen Pharmaceuticals: Other: The department has received partial funding from Janssen Pharmaceuticals. Wahlin:Gilead: Consultancy, Honoraria, Research Funding; Roche: Research Funding. Smedby:Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.

Ocular involvement as first sign of isolated CNS relapse in diffuse large B-cell lymphoma

2006 ◽  
Vol 7 (3) ◽  
pp. 274 ◽  
Author(s):  
Angela Ferrari ◽  
Mario Luppi ◽  
Andrea Lazzerini ◽  
Leonardo Potenza ◽  
Gian Maria Cavallini ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Ocular Involvement ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Large B Cell

scholarly journals New nomograms based on treatment outcome and prognostic factors for patients with spinal diffuse large B-cell lymphoma: A population‐based study

2020 ◽  
Author(s):  
Ben Wang ◽  
Lijie Chen ◽  
Boda Chen ◽  
Chenglong Xie ◽  
Zhenxuan Shao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treatment Method ◽  
Population Based ◽  
Cancer Specific Survival ◽  
Internal Validation ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Spinal diffuse large B-cell lymphoma (DLBCL) was a rare and malignant tumor, while few studies researched the prognostic factors. The prognostic factors which might have impacts on spinal DLBCL was not clear. Although chemotherapy was recognized as an optimal treatment method, but the curative effect of radiotherapy and surgery were controversial. Methods: The records of patients with spinal DLBCL were selected from the SEER database from 1991 to 2016. The incidence obtained by database was analyzed by Joinpoint Regression Program. The optimal cut-off values of age and year of diagnosis were identified by X-tail program. Univariate and multivariate survival analysis were calculated to identify independent prognostic factors. Prognostic factors were included to predict the survival possibility compared with 5 years of overall (OS) and cancer-specific survival (CSS) via the new nomograms. Results: A total of 917 patients were enrolled. Age, year of diagnosis and chemotherapy were demonstrated as independent prognostic factors for CSS and OS, and primary site was another independent prognostic factor for CSS. However, radiotherapy and surgery might be ineffective in survival. All factors were included to generate the nomograms for CSS and OS. The concordance indices (C-index) for internal validation of OS and CSS prediction were 0.697 (95%CI: 0.662-0.732) and 0.709 (95%CI: 0.692- 0.727) respectively. Conclusions: Age and year of diagnosis are closely associated with the prognosis of spinal DLBCL, and chemotherapy is an ideal treatment modality. The new nomogram is a favourable tool to evaluate the survival possibility, and is benefit for the oncologist to make clinical decisions.

scholarly journals Relapses after Achieving EFS24 in Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 454-454 ◽  
Author(s):  
Yucai Wang ◽  
Umar Farooq ◽  
Brian K. Link ◽  
Mehrdad Hefazi ◽  
Cristine Allmer ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Newly Diagnosed ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: The addition of Rituximab to chemotherapy has significantly improved the outcome of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients treated with immunochemotherapy for DLBCL who achieve EFS24 (event-free for 2 years after diagnosis) have an overall survival equivalent to that of the age- and sex-matched general population. Relapses after achieving EFS24 have been considered to be unusual but have been understudied. We sought to define the rate, clinical characteristics, treatment pattern, and outcomes of such relapses. Methods: 1448 patients with newly diagnosed DLBCL from March 2002 to June 2015 were included. Patients were enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, treated per physician choice (predominantly R-CHOP immunochemotherapy) and followed prospectively. An event was defined as progression or relapse, unplanned re-treatment after initial therapy, or death from any cause. Cumulative incidence of relapse and non-relapse mortality after achieving EFS24 were analyzed as competing events using Gray's test in the EZR software. Post-relapse survival was defined as time from relapse to death from any cause and analyzed using Kaplan-Meier method in SPSS (V22). Results: Among the 1448 patients, 1260 (87%) had DLBCL alone at diagnosis, and 188 (13%) had concurrent indolent lymphoma (follicular lymphoma 115, marginal zone lymphoma 18, chronic lymphocytic leukemia 14, lymphoplasmacytic lymphoma 4, unspecified 37) at diagnosis. After a median follow-up of 83.9 months, 896 patients achieved EFS24. For all 896 patients who achieved EFS24, the cumulative incidence of relapse (CIR) was 5.7%, 9.3% and 13.2%, respectively, at 2, 5 and 10 years after achieving EFS24. Patients with concurrent indolent lymphoma at diagnosis had a higher CIR compared to those with DLBCL alone at diagnosis (10.2 vs 4.8% at 2 years, 15.7 vs 8.0% at 5 years, 28.8 vs 9.7% at 10 years, P<0.001; Figure 1). There were a total of 84 patients who relapsed after achieving EFS24. The median age at initial diagnosis was 66 years (range 35-92), and 48 (57%) were male. At diagnosis, 11 (13%) had ECOG PS >1, 37 (50%) had LDH elevation, 62 (74%) were stage III-IV, 14 (17%) had more than 1 extranodal site, and 26 (31%) were poor risk by R-IPI score. There were 58 patients with DLBCL alone at diagnosis who relapsed after achieving EFS24, and 38 (75%) relapsed with DLBCL, 13 (25%) relapsed with indolent lymphoma (predominantly follicular lymphoma), and pathology was unknown in 7 patients. In contrast, there were 26 patients with concurrent indolent lymphoma at diagnosis who relapsed after achieving EFS24, and 9 (41%) relapsed with DLBCL, 13 (59%) relapsed with indolent lymphoma, and pathology was unknown in 4 patients. In the 47 patients who relapsed with DLBCL after achieving EFS24, 45% received intensive salvage chemotherapy, 19% received regular intensity chemotherapy, 9% received CNS directed chemotherapy, and 36% went on to receive autologous stem cell transplant (ASCT). In the 26 patients who relapsed with indolent lymphoma after achieving EFS24, 27% were initially observed, 54% received regular intensity chemotherapy, 4% received intensive salvage chemotherapy, and 19% received ASCT after subsequent progression. The median post-relapse survival (PRS) for all patients with a relapse after achieving EFS24 was 38.0 months (95% CI 27.5-48.5). The median PRS for patients who relapsed with DLBCL and indolent lymphoma after achieving EFS24 were 29.9 (19.9-39.9) and 89.9 (NR-NR) months, respectively (P=0.002; Figure 2). Conclusions: Relapses after achieving EFS24 in patients with DLBCL were uncommon in the rituximab era. Patient with DLBCL alone at diagnosis can relapse with either DLBCL or indolent lymphoma (3:1 ratio). Patients with concurrent DLBCL and indolent lymphoma at diagnosis had a significantly higher CIR, and relapses with DLBCL and indolent lymphoma were similar (2:3 ratio). Even with high intensity salvage chemotherapy and consolidative ASCT, patients who relapsed with DLBCL had a significantly worse survival compared to those who relapsed with indolent lymphoma. Late relapses with DLBCL remain clinically challenging, with a median survival of 2.5 years after relapse. Figure 1. Figure 1. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Takeda: Research Funding; Pfizer: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Merck & Co: Research Funding; Bristol-Myers Squibb: Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

scholarly journals Intrathecal (IT) Chemotherapy for Central Nervous System (CNS) Prophylaxis in Diffuse Large B-Cell Lymphoma (DLBCL): A Single Centre Retrospective Observational Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Luke Attwell ◽  
Benjamin Gray ◽  
Rachel Hall ◽  
Sally Killick ◽  
Helen McCarthy ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma ◽  
Cns Relapse ◽  
Educational Meetings ◽  
Large B Cell

Introduction: CNS relapse of DLBCL is associated with poor prognosis. Estimated incidence varies between 1.9 and 8.4%1. The CNS-International prognostic index (IPI)2 help risk stratify and estimate the 2-year risk of CNS relapse in DLBCL patients treated with R-CHOP chemotherapy. CNS prophylaxis is indicated in patients with a high risk of CNS relapse (a score of ≥4 equated to a 10.2% risk). High-risk DLBCL patients outside the CNS-IPI system include double/triple-hit (MYC/BCL-2/BCL-6 translocations) lymphoma, HIV lymphoma, testicular lymphoma, primary cutaneous lymphoma-leg type, stage IE breast lymphoma3. IT methotrexate or cytarabine administered during the course of systemic chemotherapy has been the most widely employed method of CNS prophylaxis but there is paucity of data validating its efficacy. Aim: The primary aim of the study was to evaluate the CNS relapse rates in DLBCL patients who received CNS prophylaxis. Patients and Methods: This was a single-centre retrospective observational study conducted in a district general hospital. Data was extracted from the regional (Dorset Cancer Network) DLBCL database and laboratory reports for CSF analysis at the time of the first intrathecal chemotherapy. Medical records of patients with DLBCL who received CNS prophylaxis were evaluated for the following patient-related and disease-related demographics: age at diagnosis, gender, stage, systemic treatment, CNS prophylaxis, treatment response, remission duration, systemic relapse rates, CNS relapse rates and survival. CNS-IPI scores were retrospectively calculated and additional indications evaluated for patients who received CNS prophylaxis. Results: Between 2013 and 2018, 178 patients were diagnosed with DLBCL. All patients were treated with RCHOP chemo-immunotherapy. CNS prophylaxis was administered in 47 (26%) patients. Median age was 69 years (range 20-86 years) and 62% were males. All 47 patients (100%) received IT methotrexate as CNS prophylaxis, with 43 (91%) receiving all of the planned 4 doses of IT methotrexate 12.5 mg each. A CNS-IPI score of ³4 was present in 31 (66%) patients, and a score of 2-3 in 9 (19%) patients. Additional risk factors identified included testicular lymphoma in 3 patients, breast lymphoma in 2 patients and oropharyngeal lymphoma in 2 patients. Ten (21%) patients received their treatment at the outset with courses 1-4 of R-CHOP. Of the 47 patients who received CNS prophylaxis, 5 (10%) relapsed; all had isolated CNS lymphoma at relapse. Median time to CNS relapse was 25 months (range 12-36 months) from initial diagnosis of DLBCL. Median survival after CNS relapse was 5 months (range 2-9 months). Of the remaining 141 patients, 2 patients relapsed with isolated CNS lymphoma. Conclusion: Although the overall incidence was low (4%), CNS relapse was observed in 10% of high-risk patients all of whom received CNS prophylaxis with IT methotrexate. The efficacy of CNS prophylaxis with IT chemotherapy remains unproven. There is no randomised study to show that IT prophylaxis alone is effective. Current British guidelines recommend high-dose intravenous methotrexate over IT methotrexate if patient's physiological fitness and renal function are acceptable4. The median age in our cohort was 69 years which makes it challenging to deliver dose-intensive systemic therapy concurrently with intravenous high-dose methotrexate. The role of CNS prophylaxis in high-risk patients including its efficacy and safety in older patients need further evaluation in prospective randomised studies. References Eyre T et al.Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review. Hematologica. 2019;105(7):1914-1924.Norbert Schmitz et al.CNS International prognostic Index: A risk model for CNS relapse in patients with diffuse large B-cell lymphoma treated with R-CHOPJ Clin Oncol 2016; 34:3150-3156.Andrew D Zelenetz et al.National Comprehensive Cancer Network (NCCN) Guidelines: B-Cell Lymphomas.Version 2.2020.Pamela McKay et al.The prevention of central nervous system relapse in diffuse large B-cell lymphoma: a British Society for Haematology good practice paper. Onlinelibrary.wiley.com. 2020. Available from: https://onlinelibrary.wiley.com/doi/epdf/10.1111/bjh.16866 Disclosures Hall: Janssen:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Karyopharm:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Takeda:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings;Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: sponsored for educational meetings.Killick:Celgene:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Jazz Pharmaceuticals:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Novartis:Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending educational meetings;Gilead:Honoraria, Other: Support for attending education meetings.McCarthy:Janssen:Honoraria;Abbvie:Membership on an entity's Board of Directors or advisory committees.Walewska:AbbVie:Other: sponsored for educational meetings, Speakers Bureau;Janssen:Other: sponsored for educational meetings, Speakers Bureau;Gilead:Speakers Bureau;Astra Zeneca:Membership on an entity's Board of Directors or advisory committees.Chacko:Astellas:Honoraria;Daiichi-Sankyo:Honoraria;Novartis:Honoraria, Other: Travel Grants;Gilead:Other: Travel grants;Jazz Pharmaceuticals:Other: Travel grants;Celgene:Other: Travel grants.

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