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1. Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma : updated data with mivavotinib (TAK-659/CB-659)

Author

Gordon, Leo I, Karmali, Reem, Kaplan, Jason B, Popat, Rakesh, Burris, Howard A, Ferrari, Silvia, Madan, Sumit, Patel, Manish R, Gritti, Giuseppe, El-Sharkawi, Dima, Chau, F Ian, Radford, John, de Oteyza, Jaime Pérez, Zinzani, Pier Luigi, Iyer, Swaminathan P, Townsend, William, Miao, Harry, Proscurshim, Igor, Wang, Shining, Katyayan, Shilpi, Yuan, Ying, Zhu, Jiaxi, Stumpo, Kate, Shou, Yaping, Carpio, Cecilia, Bosch, Francesc, Institut Català de la Salut, [Gordon LI, Karmali R, Kaplan JB] Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, USA. [Popat R] Department of Haematology, NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK. [Burris HA 3rd] Drug Development, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, USA. [Ferrari S] Dipartimento di Oncologia ed Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy. [Carpio C] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Bosch F] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Cèl·lules B - Tumors - Tractament, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Sang - Malalties - Tractament, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Protein Kinase Inhibitors/adverse effects, Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protein Kinase Inhibitors [CHEMICALS AND DRUGS], enfermedades hematológicas y linfáticas::enfermedades linfáticas::trastornos linfoproliferativos::linfoma::linfoma no Hodgkin::linfoma de células B::linfoma de células B grandes difuso [ENFERMEDADES], Humans, Syk Kinase, Other subheadings::/therapeutic use [Other subheadings], neoplasias::neoplasias por localización::neoplasias hematológicas [ENFERMEDADES], TAK-659, Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Lymphoma::Lymphoma, Non-Hodgkin::Lymphoma, B-Cell::Lymphoma, Large B-Cell, Diffuse [DISEASES], Vascular Endothelial Growth Factor Receptor-1, Manchester Cancer Research Centre, acciones y usos químicos::acciones farmacológicas::mecanismos moleculares de acción farmacológica::inhibidores enzimáticos::inhibidores de proteínas cinasas [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::/uso terapéutico [Otros calificadores], ResearchInstitutes_Networks_Beacons/mcrc, Non-Hodgkin's lymphoma, Neoplasms::Neoplasms by Site::Hematologic Neoplasms [DISEASES], SYK inhibitor, Treatment Outcome, Oncology, DLBCL, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Relapsed/refractory, Proteïnes quinases - Inhibidors - Ús terapèutic, Lymphoma, Large B-Cell, Diffuse/pathology
Abstract

Non-Hodgkin’s lymphoma; SYK inhibitor; Relapsed/refractory Linfoma no Hodgkin; Inhibidor de SYK; Recidivante/refractario Limfoma no Hodgkin; Inhibidor de SYK; Recaiguda/refractària We report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting data for the overall cohort of lymphoma patients, and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL; including an expanded cohort not included in the initial report). Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60–120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders. In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%). These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL. This study was funded by Takeda Development Center Americas, Inc. (TDCA), Lexington, MA, USA.

Published
2023
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2. Outlier detection of vital sign trajectories from COVID-19 patients

Author

Summerton, Sara, Tivey, Ann, Shotton, Rohan, Brown, Gavin, Redfern, Oliver C., Oakley, Rachel, Radford, John, and Wong, David C.

Subjects
body regions, Signal Processing (eess.SP), FOS: Computer and information sciences, Computer Science - Machine Learning, Computer Science - Human-Computer Interaction, FOS: Electrical engineering, electronic engineering, information engineering, Electrical Engineering and Systems Science - Signal Processing, psychological phenomena and processes, Machine Learning (cs.LG), Human-Computer Interaction (cs.HC)
Abstract

In this work, we present a novel trajectory comparison algorithm to identify abnormal vital sign trends, with the aim of improving recognition of deteriorating health. There is growing interest in continuous wearable vital sign sensors for monitoring patients remotely at home. These monitors are usually coupled to an alerting system, which is triggered when vital sign measurements fall outside a predefined normal range. Trends in vital signs, such as increasing heart rate, are often indicative of deteriorating health, but are rarely incorporated into alerting systems. We introduce a dynamic time warp distance-based measure to compare time series trajectories. We split each multi-variable sign time series into 180 minute, non-overlapping epochs. We then calculate the distance between all pairs of epochs. Each epoch is characterized by its mean pairwise distance (average link distance) to all other epochs, with clusters forming with nearby epochs. We demonstrate in synthetically generated data that this method can identify abnormal epochs and cluster epochs with similar trajectories. We then apply this method to a real-world data set of vital signs from 8 patients who had recently been discharged from hospital after contracting COVID-19. We show how outlier epochs correspond well with the abnormal vital signs and identify patients who were subsequently readmitted to hospital., Comment: 4 pages, 4 figures, 1 table. Accepted to EMBC 2023, to be indexed in IEEE Xplore and PubMed Medline

Published
2022
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6. First-line brentuximab vedotin plus chemotherapy to improve overall survival in patients with stage III/IV classical Hodgkin lymphoma: An updated analysis of ECHELON-1

Author

Ansell, Stephen M., Connors, Joseph M., Radford, John A., Kim, Won Seog, Gallamini, Andrea, Ramchandren, Radhakrishnan, Friedberg, Jonathan W., Advani, Ranjana H., Martin Hutchings, Evens, Andrew M., Smolewski, Piotr, Savage, Kerry J., Bartlett, Nancy L., Eom, Hyeon Seok, Abramson, Jeremy S., Dong, Cassie, Campana, Frank, Fenton, Keenan, Puhlmann, Markus, and Straus, David J.

Subjects
Cancer Research, Oncology
Abstract

7503 Background: To date, an overall survival (OS) benefit from upfront treatment for new treatment combinations over existing approaches has rarely been shown in first-line classical Hodgkin lymphoma (cHL). With the introduction of newer active therapies for relapsed/refractory disease, demonstration of improved OS with first-line therapy has been challenging. In ECHELON-1 (NCT01712490), 5-year follow-up analyses supported the long-term progression-free survival (PFS) benefit with first-line brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in patients (pts) with stage III/IV cHL, independent of interim positron emission tomography status. A+AVD had a manageable long-term safety profile, with numerically fewer second malignancies and a greater number of pregnancies reported vs ABVD (Connors et al, NEJM 2018; Straus et al, Lancet Haematol 2021). We report a prespecified OS analysis after approximately 6 years’ follow-up (cut-off, June 1, 2021). Methods: Pts were randomized 1:1 to receive up to 6 cycles of A+AVD (n = 664) or ABVD (n = 670) on day 1 and 15 every 28 days. OS was the key secondary endpoint and was an event-driven, pre-specified, alpha-controlled analysis in the intention to treat population. Results: At a median follow-up of 73 months, 39 and 64 OS events occurred in A+AVD and ABVD arms, respectively: OS significantly favored A+AVD vs ABVD (HR 0.590; 95% confidence interval [CI] 0.396–0.879; p = 0.009). Estimated 6-year OS rates (95% CI) were 93.9% (91.6–95.5) vs 89.4% (86.6–91.7) with A+AVD vs ABVD, respectively. There was a consistent OS benefit for A+AVD vs ABVD across prespecified subgroups. The 6-year PFS estimate was 82.3% (79.1–85.0) vs 74.5% (70.8–77.7) with A+AVD vs ABVD, respectively (HR 0.678 [95% CI 0.532–0.863]). Overall, A+AVD had a comparable long-term safety profile to ABVD. Treatment-emergent peripheral neuropathy continued to resolve or improve in both arms, with 86% (379/443) and 87% (249/286) of cases in the A+AVD and ABVD arms either completely resolving (72% vs 79%) or improving (14% vs 8%) by last follow-up. Fewer second malignancies were reported in the A+AVD vs ABVD arm (23 vs 32). More female patients reported pregnancy (49 vs 28) or live births (42 vs 19 in females) in the A+AVD vs the ABVD arm; no stillbirths were reported. No new safety signals were identified. Conclusions: A+AVD treatment resulted in a statistically significant 41% reduction in the risk of death vs ABVD, with a manageable safety profile consistent with prior reports. These outcomes confirm A+AVD as a preferred option for pts with previously untreated stage III/IV cHL. Clinical trial information: NCT01712490.

Published
2022
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7. Quantitative assessment of interim PET in Hodgkin lymphoma: An evaluation of the qPET method in adult patients in the RAPID trial

Author

Georgi, Thomas W., Kurch, Lars, Hasenclever, Dirk, Warbey, Victoria S., Pike, Lucy, Radford, John, Sabri, Osama, Kluge, Regine, and Barrington, Sally F.

Subjects
Clinical Oncology, Adult, Male, Adolescent, Lymphoma, Imaging Techniques, Science, Cancer Treatment, Radiation Therapy, Neuroimaging, Research and Analysis Methods, Pathology and Laboratory Medicine, Pediatrics, Diagnostic Radiology, Hematologic Cancers and Related Disorders, Cancer Chemotherapy, Young Adult, Signs and Symptoms, Drug Therapy, Diagnostic Medicine, Positron Emission Tomography Computed Tomography, Antineoplastic Combined Chemotherapy Protocols, Medicine and Health Sciences, Chemotherapy, Humans, Tomography, Aged, Manchester Cancer Research Centre, Pharmaceutics, ResearchInstitutes_Networks_Beacons/mcrc, Radiology and Imaging, Cancers and Neoplasms, Biology and Life Sciences, Hematology, Middle Aged, Hodgkin Disease, Oncology, Lesions, Medicine, Lymphomas, Female, Clinical Medicine, Positron Emission Tomography, Research Article, Neuroscience
Abstract

AimqPET is a quantitative method used to assess FDG-PET response in lymphoma. qPET was developed using 898 scans from children with Hodgkin Lymphoma (HL) in the EuroNet-PHL-C1 (C1) trial. The aim of this study was to determine if qPET could be applied as an alternative response method in adults in the RAPID trial.MethodsPET-CT scans performed after 3 cycles of ABVD in RAPID were re-evaluated by an independent reader, blinded to PET results and outcome in RAPID. All initially involved regions were assessed visually and by qPET. The distribution of qPET measurements was compared for RAPID and C1 patients. Previously published qPET thresholds corresponding to visual DS (vDS) of 1-5 in C1 were used to derive quantitative DS (qDS) for RAPID patients.ResultsPET-CT scans were available for 450 patients from RAPID. vDS were 1 (171 scans), 2 (153 scans), 3 (72 scans), 4 (31 scans) and 5 (23 scans) respectively. The distribution of qPET values was similar to C1 patients, with a unimodal 'normal' distribution and a long tail to the right, suggestive of favorable response in the majority and less favorable response in the minority with outlying values. qPET thresholds from C1 applied in RAPID patients gave 86% concordance for vDS and qDS. There was 97% concordance for complete metabolic response (CMR; DS 1-3) vs. no-CMR using the Lugano classification.ConclusionqPET which was developed in pediatric patients receiving more intensive OEPA chemotherapy, was a suitable quantitative method for assessing response in adult patients treated with ABVD in a response-adapted setting in the RAPID trial.

Published
2020
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9. Exploring severe mental illness and diabetes : protocol for a longitudinal observational and qualitative mixed methods study

Author

Bellass, Susan, Taylor, Johanna, Han, Lu, Prady, Stephanie Louise, Shiers, David, Jacobs, Rowena, Holt, Richard, Radford, John, Gilbody, Simon, Hewitt, Catherine Elizabeth, Doran, Timothy, Alderson, Sarah L, and Siddiqi, Najma

Subjects
mental disorders
Abstract

BACKGROUND: The average life expectancy for people with a severe mental illness (SMI) such as schizophrenia or bipolar disorder is 15 to 20 years less than that for the population as a whole. Diabetes contributes significantly to this inequality, being 2 to 3 times more prevalent in people with SMI. Various risk factors have been implicated, including side effects of antipsychotic medication and unhealthy lifestyles, which often occur in the context of socioeconomic disadvantage and health care inequality. However, little is known about how these factors may interact to influence the risk of developing diabetes and poor diabetic outcomes, or how the organization and provision of health care may contribute. OBJECTIVE: This study aims to identify the determinants of diabetes and to explore variation in diabetes outcomes for people with SMI. METHODS: This study will employ a concurrent mixed methods design combining the interrogation of electronic primary care health records from the Clinical Practice Research Datalink (CPRD GOLD) with qualitative interviews with adults with SMI and diabetes, their relatives and friends, and health care staff. The study has been funded for 2 years, from September 2017 to September 2019, and data collection has recently ended. RESULTS: CPRD and linked health data will be used to explore the association of sociodemographics, illness, and health care-related factors with both the development and outcomes of type 2 diabetes in people with SMI. Experiences of managing the comorbidity and accessing health care will be explored through qualitative interviews using topic guides informed by evidence synthesis and expert consultation. Findings from both datasets will be merged to develop a more comprehensive understanding of diabetes risks, interventions, and outcomes for people with SMI. Findings will be translated into recommendations for interventions and services using co-design workshops. CONCLUSIONS: Improving diabetes outcomes for people with SMI is a high-priority area nationally and globally. Understanding how risk factors combine to generate high prevalence of diabetes and poor diabetic outcomes for this population is a necessary first step in developing health care interventions to improve outcomes for people with diabetes and SMI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03534921; https://clinicaltrials.gov/ct2/show/NCT03534921.

Published
2019

10. Positron Emission Tomography Score Has Greater Prognostic Significance Than Pretreatment Risk Stratification in Early-Stage Hodgkin Lymphoma in the UK RAPID Study

Author

Barrington, Sally F., Phillips, Elizabeth H., Counsell, Nicholas, Hancock, Barry, Pettengell, Ruth, Johnson, Peter, Townsend, William, Culligan, Dominic, Popova, Bilyana, Clifton-Hadley, Laura, McMillan, Andrew, Hoskin, Peter, O’Doherty, Michael J., Illidge, Tim, and Radford, John

Subjects
Adult, Male, Lydia Becker Institute, Adolescent, Vinblastine, Risk Assessment, Bleomycin, Young Adult, Risk Factors, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, Antineoplastic Combined Chemotherapy Protocols, Humans, Aged, Proportional Hazards Models, Manchester Cancer Research Centre, Radiotherapy, ResearchInstitutes_Networks_Beacons/mcrc, Remission Induction, ORIGINAL REPORTS, Middle Aged, Prognosis, Combined Modality Therapy, Hodgkin Disease, United Kingdom, Dacarbazine, Treatment Outcome, Doxorubicin, Positron-Emission Tomography, Female
Abstract

PURPOSE: Accurate stratification of patients is an important goal in Hodgkin lymphoma (HL), but the role of pretreatment clinical risk stratification in the context of positron emission tomography (PET) -adapted treatment is unclear. We performed a subsidiary analysis of the RAPID trial to assess the prognostic value of pretreatment risk factors and PET score in determining outcomes.PATIENTS AND METHODS: Patients with stage IA to IIA HL and no mediastinal bulk underwent PET assessment after three cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine; 143 PET-positive patients (PET score, 3 to 5) received a fourth doxorubicin, bleomycin, vinblastine, and dacarbazine cycle and involved-field radiotherapy, and 419 patients in complete metabolic remission were randomly assigned to receive involved-field radiotherapy (n = 208) or no additional treatment (n = 211). Cox regression was used to investigate the association between PET score and pretreatment risk factors with HL-specific event-free survival (EFS).RESULTS: High PET score was associated with inferior EFS, before (P < .001) and after adjustment (P = .01) for baseline risk stratification. Only patients with a postchemotherapy PET score of 5 (uptake ≥ three times maximum liver uptake) had an increased risk of progression or HL-related death (hazard ratio, 9.4 v score of 3; 95% CI, 2.8 to 31.3 and hazard ratio, 6.7 v score of 4; 95% CI, 1.4 to 31.7). Patients with a PET score of 5 also had inferior progression-free and overall survival. There was no association between European Organisation for Research and Treatment of Cancer or German Hodgkin Study Group risk group and EFS, before or after adjusting for PET score (all P > .4).CONCLUSION: In RAPID, a positive PET scan did not carry uniform prognostic weight; only a PET score of 5 was associated with inferior outcomes. This suggests that in future trials involving patients without B symptoms or mediastinal bulk, a score of 5 rather than a positive PET result should be used to guide treatment escalation in early-stage HL.

Published
2019
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12. Additional file 1: of Dental caries experience, care index and restorative index in children with learning disabilities and children without learning disabilities; a systematic review and meta-analysis

Author

Robertson, Mark, Schwendicke, Falk, Araujo, Mariana, Radford, John, Harris, Jenny, McGregor, Scott, and Innes, Nicola

Abstract

Appendix 1: Newcastle-Ottawa Scale Risk of Bias Matrix; Appendix 2: data extraction tables from included studies. (DOCX 130 kb)

Published
2019
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16. Supplemental_Material – Supplemental material for Discussing factors associated with quality of life in cancer follow-up appointments: a preliminary test of a pragmatic model for clinical practice

Author

Lindner, Oana C, McCabe, Martin G, Boele, Florien, Mayes, Andrew, Talmi, Deborah, Radford, John, and Wearden, Alison

Subjects
FOS: Clinical medicine, 110604 Sports Medicine, FOS: Health sciences, 110904 Neurology and Neuromuscular Diseases, 110314 Orthopaedics
Abstract

Supplemental material, Supplemental_Material for Discussing factors associated with quality of life in cancer follow-up appointments: a preliminary test of a pragmatic model for clinical practice by Oana C Lindner, Martin G McCabe, Florien Boele, Andrew Mayes, Deborah Talmi, John Radford and Alison Wearden in Clinical Rehabilitation

Published
2018
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17. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma

Author

Connors, Joseph M, Jurczak, Wojciech, Straus, David J, Ansell, Stephen M, Kim, Won S, Gallamini, Andrea, Younes, Anas, Alekseev, Sergey, Illés, Árpád, Picardi, Marco, Lech-Maranda, Ewa, Oki, Yasuhiro, Feldman, Tatyana, Smolewski, Piotr, Savage, Kerry J, Bartlett, Nancy L, Walewski, Jan, Chen, Robert, Ramchandren, Radhakrishnan, Zinzani, Pier L, Cunningham, David, Rosta, Andras, Josephson, Neil C, Song, Eric, Sachs, Jessica, Liu, Rachael, Jolin, Hina A, Huebner, Dirk, Radford, John, Luminari, Stefano, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Connors, J. M., Jurczak, W., Straus, D. J., Ansell, S. M., Kim, W. S., Gallamini, A., Younes, A., Alekseev, S., Illés, A., Picardi, M., Lech-Maranda, E., Oki, Y., Feldman, T., Smolewski, P., Savage, K. J., Bartlett, N. L., Walewski, J., Chen, R., Ramchandren, R., Zinzani, P. L., Cunningham, D., Rosta, A., Josephson, N. C., Song, E., Sachs, J., Liu, R., Jolin, H. A., Huebner, D., and Radford, J.

Subjects
Male, Oncology, medicine.medical_treatment, chemistry.chemical_compound, Immunologic Factor, 0302 clinical medicine, Brentuximab vedotin, anti-CD30, Brentuximab vedotin, Aged, 80 and over, Medicine (all), Orvostudományok, General Medicine, Middle Aged, Hodgkin Disease, Vinblastine, Dacarbazine, Survival Rate, 030220 oncology & carcinogenesis, Female, Human, medicine.drug, Adult, medicine.medical_specialty, Neutropenia, Adolescent, Klinikai orvostudományok, Bleomycin, Disease-Free Survival, Article, Follow-Up Studie, Young Adult, 03 medical and health sciences, Internal medicine, medicine, anti-CD30, Survival rate, Aged, Neoplasm Staging, Chemotherapy, Antineoplastic Combined Chemotherapy Protocol, business.industry, Hodgkin's lymphoma, medicine.disease, Immunoconjugate, chemistry, ABVD, Doxorubicin, business, 030215 immunology
Abstract

none 29 si This article was published on December 10, 2017. All ECHELON-1 investigators are listed in the Supplementary Appendix, available at NEJM.org Background Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma. Methods We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. Results At a median follow-up of 24.9 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.7 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.03). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.72 [95% CI, 0.44 to 1.17]; P=0.19). All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity. Conclusions A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .). mixed Joseph M. Connors; Wojciech Jurczak; David J. Straus; Stephen M. Ansell; Won S. Kim; Andrea Gallamini; Anas Younes; Sergey Alekseev; Árpád Illés; Marco Picardi; Ewa Lech-Maranda; Yasuhiro Oki; Tatyana Feldman; Piotr Smolewski; Kerry J. Savage; Nancy L. Bartlett; Jan Walewski; Robert Chen; Radhakrishnan Ramchandren; Pier L. Zinzani; David Cunningham; Andras Rosta; Neil C. Josephson; Eric Song; Jessica Sachs; Rachael Liu; Hina A. Jolin; Dirk Huebner; John Radford for the ECHELON-1 Study Group Joseph M. Connors; Wojciech Jurczak; David J. Straus; Stephen M. Ansell; Won S. Kim; Andrea Gallamini; Anas Younes; Sergey Alekseev; Árpád Illés; Marco Picardi; Ewa Lech-Maranda; Yasuhiro Oki; Tatyana Feldman; Piotr Smolewski; Kerry J. Savage; Nancy L. Bartlett; Jan Walewski; Robert Chen; Radhakrishnan Ramchandren; Pier L. Zinzani; David Cunningham; Andras Rosta; Neil C. Josephson; Eric Song; Jessica Sachs; Rachael Liu; Hina A. Jolin; Dirk Huebner; John Radford for the ECHELON-1 Study Group

Published
2018

18. The European Hematology Association Roadmap for European Hematology Research: a consensus document

Author

Engert, Andreas, Balduini, Carlo, Brand, Anneke, Coiffier, Bertrand, Cordonnier, Catherine, Doehner, Hartmut, de Wit, Thom Duyvene, Eichinger, Sabine, Fibbe, Willem, Green, Tony, de Haas, Fleur, Iolascon, Achille, Jaffredo, Thierry, Rodeghiero, Francesco, Salles, Gilles, Schuringa, Jan Jacob, Andre, Marc, Andre-Schmutz, Isabelle, Bacigalupo, Andrea, Bochud, Pierre-Yves, den Boer, Monique, Bonini, Chiara, Camaschella, Clara, Cant, Andrew, Cappellini, Maria Domenica, Cazzola, Mario, Lo Celso, Cristina, Dimopoulos, Meletios, Douay, Luc, Dzierzak, Elaine, Einsele, Hermann, Ferreri, Andres, De Franceschi, Lucia, Gaulard, Philippe, Gottgens, Berthold, Greinacher, Andreas, Gresele, Paolo, Gribben, John, de Haan, Gerald, Hansen, John-Bjarne, Hochhaus, Andreas, Kadir, Rezan, Kaveri, Srini, Kouskoff, Valerie, Kuehne, Thomas, Kyrle, Paul, Ljungman, Per, Maschmeyer, Georg, Mendez-Ferrer, Simon, Milsom, Michael, Mummery, Christine, Ossenkoppele, Gert, Pecci, Alessandro, Peyvandi, Flora, Philipsen, Sjaak, Reitsma, Pieter, Maria Ribera, Jose, Risitano, Antonio, Rivella, Stefano, Ruf, Wolfram, Schroeder, Timm, Scully, Marie, Socie, Gerard, Staal, Frank, Stanworth, Simon, Stauder, Reinhard, Stilgenbauer, Stephan, Tamary, Hannah, Theilgaard-Monch, Kim, Thein, Swee Lay, Tilly, Herve, Trneny, Marek, Vainchenker, William, Vannucchi, Alessandro Maria, Viscoli, Claudio, Vrielink, Hans, Zaaijer, Hans, Zanella, Alberto, Zolla, Lello, Zwaginga, Jaap Jan, Martinez, Patricia Aguilar, van den Akker, Emile, Allard, Shubha, Anagnou, Nicholas, Andolfo, Immacolata, Andrau, Jean-Christophe, Angelucci, Emanuele, Anstee, David, Aurer, Igor, Avet-Loiseau, Herve, Aydinok, Yesim, Bakchoul, Tamam, Balduini, Alessandra, Barcellini, Wilma, Baruch, Dominique, Baruchel, Andre, Bayry, Jagadeesh, Bento, Celeste, van den Berg, Anke, Bernardi, Rosa, Bianchi, Paola, Bigas, Anna, Biondi, Andrea, Bohonek, Milos, Bonnet, Dominique, Borchmann, Peter, Borregaard, Niels, Braekkan, Sigrid, van den Brink, Marcel, Brodin, Ellen, Bullinger, Lars, Buske, Christian, Butzeck, Barbara, Cammenga, Jorg, Campo, Elias, Carbone, Antonino, Cervantes, Francisco, Cesaro, Simone, Charbord, Pierre, Claas, Frans, Cohen, Hannah, Conard, Jacqueline, Coppo, Paul, Vives Corrons, Joan-Lluis, da Costa, Lydie, Davi, Frederic, Delwel, Ruud, Dianzani, Irma, Domanovic, Dragoslav, Donnelly, Peter, Drnovsek, Tadeja Dovc, Dreyling, Martin, Du, Ming-Qing, Dufour, Carlo, Durand, Charles, Efremov, Dimitar, Eleftheriou, Androulla, Elion, Jacques, Emonts, Marieke, Engelhardt, Monika, Ezine, Sophie, Falkenburg, Fred, Favier, Remi, Federico, Massimo, Fenaux, Pierre, Fitzgibbon, Jude, Flygare, Johan, Foa, Robin, Forrester, Lesley, Galacteros, Frederic, Garagiola, Isabella, Gardiner, Chris, Garraud, Olivier, van Geet, Christel, Geiger, Hartmut, Geissler, Jan, Germing, Ulrich, Ghevaert, Cedric, Girelli, Domenico, Godeau, Bertrand, Goekbuget, Nicola, Goldschmidt, Hartmut, Goodeve, Anne, Graf, Thomas, Graziadei, Giovanna, Griesshammer, Martin, Gruel, Yves, Guilhot, Francois, von Gunten, Stephan, Gyssens, Inge, Halter, Jorg, Harrison, Claire, Harteveld, Cornelis, Hellstrom-Lindberg, Eva, Hermine, Olivier, Higgs, Douglas, Hillmen, Peter, Hirsch, Hans, Hoskin, Peter, Huls, Gerwin, Inati, Adlette, Johnson, Peter, Kattamis, Antonis, Kiefel, Volker, Kleanthous, Marina, Klump, Hannes, Krause, Daniela, Hovinga, Johanna Kremer, Lacaud, Georges, Lacroix-Desmazes, Sebastien, Landman-Parker, Judith, LeGouill, Steven, Lenz, Georg, von Lilienfeld-Toal, Marie, von Lindern, Marieke, Lopez-Guillermo, Armando, Lopriore, Enrico, Lozano, Miguel, MacIntyre, Elizabeth, Makris, Michael, Mannhalter, Christine, Martens, Joost, Mathas, Stephan, Matzdorff, Axel, Medvinsky, Alexander, Menendez, Pablo, Migliaccio, Anna Rita, Miharada, Kenichi, Mikulska, Malgorzata, Minard, Veronique, Montalban, Carlos, de Montalembert, Mariane, Montserrat, Emili, Morange, Pierre-Emmanuel, Mountford, Joanne, Muckenthaler, Martina, Mueller-Tidow, Carsten, Mumford, Andrew, Nadel, Bertrand, Navarro, Jose-Tomas, el Nemer, Wassim, Noizat-Pirenne, France, O'Mahony, Brian, Oldenburg, Johannes, Olsson, Martin, Oostendorp, Robert, Palumbo, Antonio, Passamonti, Francesco, Patient, Roger, de Latour, Regis Peffault, Pflumio, Francoise, Pierelli, Luca, Piga, Antonio, Pollard, Debra, Raaijmakers, Marc, Radford, John, Rambach, Ralf, Rao, A. Koneti, Raslova, Hana, Rebulla, Paolo, Rees, David, Ribrag, Vincent, Rijneveld, Anita, Rinalducci, Sara, Robak, Tadeusz, Roberts, Irene, Rodrigues, Charlene, Rosendaal, Frits, Rosenwald, Andreas, Rule, Simon, Russo, Roberta, Saglio, Guiseppe, Sanchez, Mayka, Scharf, Ruediger E., Schlenke, Peter, Semple, John, Sierra, Jorge, So-Osman, Cynthia, Manuel Soria, Jose, Stamatopoulos, Kostas, Stegmayr, Bernd, Stunnenberg, Henk, Swinkels, Dorine, Taborda Barata, Joao Pedro, Taghon, Tom, Taher, Ali, Terpos, Evangelos, Thachil, Jecko, Tissot, Jean Daniel, Touw, Ivo, Toye, Ash, Trappe, Ralf, Traverse-Glehen, Alexandra, Unal, Sule, Vaulont, Sophie, Viprakasit, Vip, Vitolo, Umberto, van Wijk, Richard, Wojtowicz, Agnieszka, Zeerleder, Sacha, Zieger, Barbara, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Sorbonne Paris Cité (USPC), Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Cologne [Cologne], Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Department of Internal Medicine I, Medizinische Universität Wien = Medical University of Vienna, Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ege Üniversitesi, Engert, Andrea, Balduini, Carlo, Brand, Anneke, Coiffier, Bertrand, Cordonnier, Catherine, Döhner, Hartmut, De Wit, Thom Duyvené, Eichinger, Sabine, Fibbe, Willem, Green, Tony, De Haas, Fleur, Iolascon, Achille, Jaffredo, Thierry, Rodeghiero, Francesco, Sall Es, Gille, Schuringa, Jan Jacob, André, Marc, Andre Schmutz, Isabelle, Bacigalupo, Andrea, Bochud, Pierre Yve, Den Boer, Monique, Bonini, Chiara, Camaschella, Clara, Cant, Andrew, Cappellini, Maria Domenica, Cazzola, Mario, Celso, Cristina Lo, Dimopoulos, Meletio, Douay, Luc, Dzierzak, Elaine, Einsele, Hermann, Ferreri, André, De Franceschi, Lucia, Gaulard, Philippe, Gottgens, Berthold, Greinacher, Andrea, Gresele, Paolo, Gribben, John, De Haan, Gerald, Hansen, John Bjarne, Hochhaus, Andrea, Kadir, Rezan, Kaveri, Srini, Kouskoff, Valerie, Kühne, Thoma, Kyrle, Paul, Ljungman, Per, Maschmeyer, Georg, Méndez Ferrer, Simón, Milsom, Michael, Mummery, Christine, Ossenkoppele, Gert, Pecci, Alessandro, Peyvandi, Flora, Philipsen, Sjaak, Reitsma, Pieter, Ribera, José Maria, Risitano, ANTONIO MARIA, Rivella, Stefano, Ruf, Wolfram, Schroeder, Timm, Scully, Marie, Socie, Gerard, Staal, Frank, Stanworth, Simon, Stauder, Reinhard, Stilgenbauer, Stephan, Tamary, Hannah, Theilgaard Mönch, Kim, Thein, Swee Lay, Tilly, Hervé, Trneny, Marek, Vainchenker, William, Vannucchi, Alessandro Maria, Viscoli, Claudio, Vrielink, Han, Zaaijer, Han, Zanella, Alberto, Zolla, Lello, Zwaginga, Jaap Jan, Martinez, Patricia Aguilar, Van Den Akker, Emile, Allard, Shubha, Anagnou, Nichola, Andolfo, Immacolata, Andrau, Jean Christophe, Angelucci, Emanuele, Anstee, David, Aurer, Igor, Avet Loiseau, Hervé, Aydinok, Yesim, Bakchoul, Tamam, Balduini, Alessandra, Barcellini, Wilma, Baruch, Dominique, Baruchel, André, Bayry, Jagadeesh, Bento, Celeste, Van Den Berg, Anke, Bernardi, Rosa, Bianchi, Paola, Bigas, Anna, Biondi, Andrea, Bohonek, Milo, Bonnet, Dominique, Borchmann, Peter, Borregaard, Niel, Brækkan, Sigrid, Van Den Brink, Marcel, Brodin, Ellen, Bullinger, Lar, Buske, Christian, Butzeck, Barbara, Cammenga, Jörg, Campo, Elia, Carbone, Antonino, Cervantes, Francisco, Cesaro, Simone, Charbord, Pierre, Claas, Fran, Cohen, Hannah, Conard, Jacqueline, Coppo, Paul, Vives Corron, Joan Llui, Da Costa, Lydie, Davi, Frederic, Delwel, Ruud, Dianzani, Irma, Domanović, Dragoslav, Donnelly, Peter, Drnovšek, Tadeja Dovč, Dreyling, Martin, Du, Ming Qing, Dufour, Carlo, Durand, Charle, Efremov, Dimitar, Eleftheriou, Androulla, Elion, Jacque, Emonts, Marieke, Engelhardt, Monika, Ezine, Sophie, Falkenburg, Fred, Favier, Remi, Federico, Massimo, Fenaux, Pierre, Fitzgibbon, Jude, Flygare, Johan, Foà, Robin, Forrester, Lesley, Galacteros, Frederic, Garagiola, Isabella, Gardiner, Chri, Garraud, Olivier, Van Geet, Christel, Geiger, Hartmut, Geissler, Jan, Germing, Ulrich, Ghevaert, Cedric, Girelli, Domenico, Godeau, Bertrand, Gökbuget, Nicola, Goldschmidt, Hartmut, Goodeve, Anne, Graf, Thoma, Graziadei, Giovanna, Griesshammer, Martin, Gruel, Yve, Guilhot, Francoi, Von Gunten, Stephan, Gyssens, Inge, Halter, Jörg, Harrison, Claire, Harteveld, Corneli, Hellström Lindberg, Eva, Hermine, Olivier, Higgs, Dougla, Hillmen, Peter, Hirsch, Han, Hoskin, Peter, Huls, Gerwin, Inati, Adlette, Johnson, Peter, Kattamis, Antoni, Kiefel, Volker, Kleanthous, Marina, Klump, Hanne, Krause, Daniela, Hovinga, Johanna Kremer, Lacaud, George, Lacroix Desmazes, Sébastien, Landman Parker, Judith, Legouill, Steven, Lenz, Georg, Von Lilienfeld Toal, Marie, Von Lindern, Marieke, Lopez Guillermo, Armando, Lopriore, Enrico, Lozano, Miguel, Macintyre, Elizabeth, Makris, Michael, Mannhalter, Christine, Martens, Joost, Mathas, Stephan, Matzdorff, Axel, Medvinsky, Alexander, Menendez, Pablo, Migliaccio, Anna Rita, Miharada, Kenichi, Mikulska, Malgorzata, Minard, Véronique, Montalbán, Carlo, De Montalembert, Mariane, Montserrat, Emili, Morange, Pierre Emmanuel, Mountford, Joanne, Muckenthaler, Martina, Müller Tidow, Carsten, Mumford, Andrew, Nadel, Bertrand, Navarro, Jose Toma, El Nemer, Wassim, Noizat Pirenne, France, O’Mahony, Brian, Oldenburg, Johanne, Olsson, Martin, Oostendorp, Robert, Palumbo, Antonio, Passamonti, Francesco, Patient, Roger, De Latour, Regis Peffault, Pflumio, Francoise, Pierelli, Luca, Piga, Antonio, Pollard, Debra, Raaijmakers, Marc, Radford, John, Rambach, Ralf, Koneti Rao, A., Raslova, Hana, Rebulla, Paolo, Rees, David, Ribrag, Vincent, Rijneveld, Anita, Rinalducci, Sara, Robak, Tadeusz, Roberts, Irene, Rodrigues, Charlene, Rosendaal, Frit, Rosenwald, Andrea, Rule, Simon, Russo, Roberta, Saglio, Guiseppe, Sanchez, Mayka, Scharf, Rüdiger E., Schlenke, Peter, Semple, John, Sierra, Jorge, So Osman, Cynthia, Soria, José Manuel, Stamatopoulos, Kosta, Stegmayr, Bernd, Stunnenberg, Henk, Swinkels, Dorine, Barata, João Pedro Taborda, Taghon, Tom, Taher, Ali, Terpos, Evangelo, Thachil, Jecko, Tissot, Jean Daniel, Touw, Ivo, Toye, Ash, Trappe, Ralf, Traverse Glehen, Alexandra, Unal, Sule, Vaulont, Sophie, Viprakasit, Vip, Vitolo, Umberto, Van Wijk, Richard, Wójtowicz, Agnieszka, Zeerleder, Sacha, Zieger, Barbara, Hematology, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), University of York [York, UK], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pediatrics, Cell biology, Erasmus MC other, Pulmonary Medicine, Medical Oncology, Other departments, AII - Amsterdam institute for Infection and Immunity, Medical Microbiology and Infection Prevention, ACS - Amsterdam Cardiovascular Sciences, Clinical Haematology, Engert, A, Balduini, C, Brand, A, Coiffier, B, Cordonnier, C, Döhner, H, De, Wit, Td, Eichinger, S, Fibbe, W, Green, T, de Haas, F, Iolascon, A, Jaffredo, T, Rodeghiero, F, Salles, G, Schuringa, Jj, and the other authors of the EHA Roadmap for European Hematology, Research, Cancer Research UK, Biotechnology and Biological Sciences Research Council (BBSRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), De Wit, T, De Haas, F, Sall Es, G, Schuringa, J, André, M, Andre Schmutz, I, Bacigalupo, A, Bochud, P, Den Boer, M, Bonini, C, Camaschella, C, Cant, A, Cappellini, M, Cazzola, M, Celso, C, Dimopoulos, M, Douay, L, Dzierzak, E, Einsele, H, Ferreri, A, De Franceschi, L, Gaulard, P, Gottgens, B, Greinacher, A, Gresele, P, Gribben, J, De Haan, G, Hansen, J, Hochhaus, A, Kadir, R, Kaveri, S, Kouskoff, V, Kühne, T, Kyrle, P, Ljungman, P, Maschmeyer, G, Méndez Ferrer, S, Milsom, M, Mummery, C, Ossenkoppele, G, Pecci, A, Peyvandi, F, Philipsen, S, Reitsma, P, Ribera, J, Risitano, A, Rivella, S, Ruf, W, Schroeder, T, Scully, M, Socie, G, Staal, F, Stanworth, S, Stauder, R, Stilgenbauer, S, Tamary, H, Theilgaard Mönch, K, Thein, S, Tilly, H, Trneny, M, Vainchenker, W, Vannucchi, A, Viscoli, C, Vrielink, H, Zaaijer, H, Zanella, A, Zolla, L, Zwaginga, J, Martinez, P, Van Den Akker, E, Allard, S, Anagnou, N, Andolfo, I, Andrau, J, Angelucci, E, Anstee, D, Aurer, I, Avet Loiseau, H, Aydinok, Y, Bakchoul, T, Balduini, A, Barcellini, W, Baruch, D, Baruchel, A, Bayry, J, Bento, C, Van Den Berg, A, Bernardi, R, Bianchi, P, Bigas, A, Biondi, A, Bohonek, M, Bonnet, D, Borchmann, P, Borregaard, N, Brækkan, S, Van Den Brink, M, Brodin, E, Bullinger, L, Buske, C, Butzeck, B, Cammenga, J, Campo, E, Carbone, A, Cervantes, F, Cesaro, S, Charbord, P, Claas, F, Cohen, H, Conard, J, Coppo, P, Vives Corron, J, Da Costa, L, Davi, F, Delwel, R, Dianzani, I, Domanović, D, Donnelly, P, Drnovšek, T, Dreyling, M, Du, M, Dufour, C, Durand, C, Efremov, D, Eleftheriou, A, Elion, J, Emonts, M, Engelhardt, M, Ezine, S, Falkenburg, F, Favier, R, Federico, M, Fenaux, P, Fitzgibbon, J, Flygare, J, Foà, R, Forrester, L, Galacteros, F, Garagiola, I, Gardiner, C, Garraud, O, Van Geet, C, Geiger, H, Geissler, J, Germing, U, Ghevaert, C, Girelli, D, Godeau, B, Gökbuget, N, Goldschmidt, H, Goodeve, A, Graf, T, Graziadei, G, Griesshammer, M, Gruel, Y, Guilhot, F, Von Gunten, S, Gyssens, I, Halter, J, Harrison, C, Harteveld, C, Hellström Lindberg, E, Hermine, O, Higgs, D, Hillmen, P, Hirsch, H, Hoskin, P, Huls, G, Inati, A, Johnson, P, Kattamis, A, Kiefel, V, Kleanthous, M, Klump, H, Krause, D, Hovinga, J, Lacaud, G, Lacroix Desmazes, S, Landman Parker, J, Legouill, S, Lenz, G, Von Lilienfeld Toal, M, Von Lindern, M, Lopez Guillermo, A, Lopriore, E, Lozano, M, Macintyre, E, Makris, M, Mannhalter, C, Martens, J, Mathas, S, Matzdorff, A, Medvinsky, A, Menendez, P, Migliaccio, A, Miharada, K, Mikulska, M, Minard, V, Montalbán, C, De Montalembert, M, Montserrat, E, Morange, P, Mountford, J, Muckenthaler, M, Müller Tidow, C, Mumford, A, Nadel, B, Navarro, J, El Nemer, W, Noizat Pirenne, F, O’Mahony, B, Oldenburg, J, Olsson, M, Oostendorp, R, Palumbo, A, Passamonti, F, Patient, R, De Latour, R, Pflumio, F, Pierelli, L, Piga, A, Pollard, D, Raaijmakers, M, Radford, J, Rambach, R, Koneti Rao, A, Raslova, H, Rebulla, P, Rees, D, Ribrag, V, Rijneveld, A, Rinalducci, S, Robak, T, Roberts, I, Rodrigues, C, Rosendaal, F, Rosenwald, A, Rule, S, Russo, R, Saglio, G, Sanchez, M, Scharf, R, Schlenke, P, Semple, J, Sierra, J, So Osman, C, Soria, J, Stamatopoulos, K, Stegmayr, B, Stunnenberg, H, Swinkels, D, Barata, J, Taghon, T, Taher, A, Terpos, E, Thachil, J, Tissot, J, Touw, I, Toye, A, Trappe, R, Traverse Glehen, A, Unal, S, Vaulont, S, Viprakasit, V, Vitolo, U, Van Wijk, R, Wójtowicz, A, Zeerleder, S, Zieger, B, Andreas Engert, Carlo Balduini, Anneke Brand, Bertrand Coiffier, Catherine Cordonnier, Hartmut Döhner, Thom Duyvené de Wit, Sabine Eichinger, Willem Fibbe, Tony Green, Fleur de Haas, Achille Iolascon, Thierry Jaffredo, Francesco Rodeghiero, Gilles Salles, Jan Jacob Schuringa, the other authors of the EHA Roadmap for European Hematology Research, Anna Rita Migliaccio, EHA Roadmap for European Hematology, Research, Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Döhner, H., de Wit TD., Eichinger, S., Fibbe, W., Green, T., de Haas, F., Iolascon, A., Jaffredo, T., Rodeghiero, F., Salles, G., Schuringa, JJ., André, M., Andre-Schmutz, I., Bacigalupo, A., Bochud, PY., Boer, Md., Bonini, C., Camaschella, C., Cant, A., Cappellini, MD., Cazzola, M., Celso, CL., Dimopoulos, M., Douay, L., Dzierzak, E., Einsele, H., Ferreri, A., De Franceschi, L., Gaulard, P., Gottgens, B., Greinacher, A., Gresele, P., Gribben, J., de Haan, G., Hansen, JB., Hochhaus, A., Kadir, R., Kaveri, S., Kouskoff, V., Kühne, T., Kyrle, P., Ljungman, P., Maschmeyer, G., Méndez-Ferrer£££Simón£££ S., Milsom, M., Mummery, C., Ossenkoppele, G., Pecci, A., Peyvandi, F., Philipsen, S., Reitsma, P., Ribera, JM., Risitano, A., Rivella, S., Ruf, W., Schroeder, T., Scully, M., Socie, G., Staal, F., Stanworth, S., Stauder, R., Stilgenbauer, S., Tamary, H., Theilgaard-Mönch, K., Thein, SL., Tilly, H., Trneny, M., Vainchenker, W., Vannucchi, AM., Viscoli, C., Vrielink, H., Zaaijer, H., Zanella, A., Zolla, L., Zwaginga, JJ., Martinez, PA., van den Akker, E., Allard, S., Anagnou, N., Andolfo, I., Andrau, JC., Angelucci, E., Anstee, D., Aurer, I., Avet-Loiseau, H., Aydinok, Y., Bakchoul, T., Balduini, A., Barcellini, W., Baruch, D., Baruchel, A., Bayry, J., Bento, C., van den Berg, A., Bernardi, R., Bianchi, P., Bigas, A., Biondi, A., Bohonek, M., Bonnet, D., Borchmann, P., Borregaard, N., Brækkan, S., van den Brink, M., Brodin, E., Bullinger, L., Buske, C., Butzeck, B., Cammenga, J., Campo, E., Carbone, A., Cervantes, F., Cesaro, S., Charbord, P., Claas, F., Cohen, H., Conard, J., Coppo, P., Corrons, JL., Costa, Ld., Davi, F., Delwel, R., Dianzani, I., Domanović, D., Donnelly, P., Drnov?ek£££Tadeja Dovč£££ TD., Dreyling, M., Du, MQ., Dufour, C., Durand, C., Efremov, D., Eleftheriou, A., Elion, J., Emonts, M., Engelhardt, M., Ezine, S., Falkenburg, F., Favier, R., Federico, M., Fenaux, P., Fitzgibbon, J., Flygare, J., Foà, R., Forrester, L., Galacteros, F., Garagiola, I., Gardiner, C., Garraud, O., van Geet, C., Geiger, H., Geissler, J., Germing, U., Ghevaert, C., Girelli, D., Godeau, B., Gökbuget, N., Goldschmidt, H., Goodeve, A., Graf, T., Graziadei, G., Griesshammer, M., Gruel, Y., Guilhot, F., von Gunten, S., Gyssens, I., Halter, J., Harrison, C., Harteveld, C., Hellström-Lindberg, E., Hermine, O., Higgs, D., Hillmen, P., Hirsch, H., Hoskin, P., Huls, G., Inati, A., Johnson, P., Kattamis, A., Kiefel, V., Kleanthous, M., Klump, H., Krause, D., Hovinga, JK., Lacaud, G., Lacroix-Desmazes, S., Landman-Parker, J., LeGouill, S., Lenz, G., von Lilienfeld-Toal, M., von Lindern, M., Lopez-Guillermo, A., Lopriore, E., Lozano, M., MacIntyre, E., Makris, M., Mannhalter, C., Martens, J., Mathas, S., Matzdorff, A., Medvinsky, A., Menendez, P., Migliaccio, AR., Miharada, K., Mikulska, M., Minard, V., Montalbán, C., de Montalembert, M., Montserrat, E., Morange, PE., Mountford, J., Muckenthaler, M., Müller-Tidow, C., Mumford, A., Nadel, B., Navarro, JT., Nemer, We., Noizat-Pirenne, F., O'Mahony, B., Oldenburg, J., Olsson, M., Oostendorp, R., Palumbo, A., Passamonti, F., Patient, R., Peffault, R., Pflumio, F., Pierelli, L., Piga, A., Pollard, D., Raaijmakers, M., Radford, J., Rambach, R., Rao, AK., Raslova, H., Rebulla, P., Rees, D., Ribrag, V., Rijneveld, A., Rinalducci, S., Robak, T., Roberts, I., Rodrigues, C., Rosendaal, F., Rosenwald, A., Rule, S., Russo, R., Saglio, G., Sanchez, M., Scharf, RE., Schlenke, P., Semple, J., Sierra, J., So-Osman, C., Soria, JM., Stamatopoulos, K., Stegmayr, B., Stunnenberg, H., Swinkels, D., Barata£££João Pedro Taborda£££ JP., Taghon, T., Taher, A., Terpos, E., Thachil, J., Tissot, JD., Touw, I., Toye, A., Trappe, R., Traverse-Glehen, A., Unal, S., Vaulont, S., Viprakasit, V., Vitolo, U., van Wijk, R., Wójtowicz, A., Zeerleder, S., Zieger, B., Stem Cell Aging Leukemia and Lymphoma (SALL), and Çocuk Sağlığı ve Hastalıkları

Subjects
0301 basic medicine, Cancer Research, diagnosis, Health Services for the Aged, ACUTE PROMYELOCYTIC LEUKEMIA, Medizin, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, EHA Roadmap for European Hematology Research, Antineoplastic Agent, 0302 clinical medicine, European Hematology Association Roadmap, Germany, PERIPHERAL T-CELL, Medicine and Health Sciences, Hematopoiesi, genetics, Molecular Targeted Therapy, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, Hematology, Genome, Hematopoietic Stem Cell Transplantation, Anemia, Awareness, Supply & distribution, Combined Modality Therapy, 3. Good health, Europe, THROMBOPOIETIN-RECEPTOR AGONISTS, Blood Disorder, Italy, Austria, haematology, Medicine, France, Immunotherapy, Infection, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Human, medicine.medical_specialty, Thrombopoietin Receptor Agonists, Consensus, Patients, Immunology, Antineoplastic Agents, Blood Coagulation, Gene Expression Profiling, Genetic Therapy, Genome, Human, Hematologic Diseases, Hematopoiesis, Humans, Consensu, [SDV.CAN]Life Sciences [q-bio]/Cancer, ACUTE MYELOID-LEUKEMIA, 1102 Cardiovascular Medicine And Haematology, Genetic therapy, methods, 03 medical and health sciences, blood, Internal medicine, medicine, Hematologi, THROMBOTIC THROMBOCYTOPENIC PURPURA, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, ACUTE LYMPHOBLASTIC-LEUKEMIA, therapy, business.industry, CHRONIC LYMPHOCYTIC-LEUKEMIA, supply & distribution, STEM-CELL TRANSPLANTATION, economics, Hematologic Disease, Opinion Article, Transplantation, 030104 developmental biology, Family medicine, therapeutic use, drug effects, RANDOMIZED-CONTROLLED-TRIAL, HEMOLYTIC-UREMIC SYNDROME, pathology, business, chemical synthesis, 030215 immunology, Stem Cell Transplantation, transplantation
Abstract

WOS: 000379156300012, PubMed ID: 26819058, The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients., Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research Council (BBSRC) [BB/L023776/1, BB/I00050X/1, BB/K021168/1]; Cancer Research UKCancer Research UK [11831]; Medical Research CouncilMedical Research Council UK (MRC) [G1000801a]; Novo Nordisk FondenNovo Nordisk [NNF12OC1015986]; British Heart FoundationBritish Heart Foundation [FS/09/039/27788]; Cancer Research UKCancer Research UK [12765]; Medical Research CouncilMedical Research Council UK (MRC) [MR/L022982/1, MC_UU_12009/8, MC_U137981013, MC_PC_12009]

Published
2016
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19. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

Author

Chen, Robert Zinzani, Pier Luigi Fanale, Michelle A. Armand, Philippe Johnson, Nathalie A. Brice, Pauline Radford, John and Ribrag, Vincent Molin, Daniel Vassilakopoulos, Theodoros P. and Tomita, Akihiro von Tresckow, Bastian Shipp, Margaret A. and Zhang, Yinghua Ricart, Alejandro D. Balakumaran, Arun and Moskowitz, Craig H. KEYNOTE-087 Investigators

Abstract

Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1-blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 (ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response >= 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease. (C) 2017 by American Society of Clinical Oncology

Published
2017

20. PET-CT for staging & early response:results from 'Response Adapted Therapy in Advanced Hodgkin Lymphoma' (RATHL) (CRUK/07/033)

Author

Barrington, Sally F, Kirkwood, Amy A, Franceschetto, Antonella, Fulham, Michael J, Roberts, Thomas H, Almquist, Helén, Brun, Eva, Hjorthaug, Karin, Viney, Zaid N, Pike, Lucy C, Federico, Massimo, Luminari, Stefano, Radford, John, Trotman, Judith, Fosså, Alexander, Berkahn, Leanne, Molin, Daniel, D'Amore, Francesco, Sinclair, Donald A, Smith, Paul, O'Doherty, Michael J, Stevens, Lindsey, and Johnson, Peter W

Abstract

International guidelines recommend PET-CT should replace CT in Hodgkin Lymphoma (HL). The aims of this study were to i) compare PET-CT with CT for staging and ii) measure agreement between expert and local readers, using a five-point scale (Deauville criteria), to adapt treatment in a clinical trial 'Response Adapted Therapy in Advanced Hodgkin Lymphoma' (RATHL) www.cancer.gov/clinicaltrials, reference NCT00678327. Patients were staged for the trial using clinical assessment, CT and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core labs. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement amongst experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11) or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterisation of lesions in the vast majority. Five patients were upstaged by marrow biopsy; 7 by contrast-enhanced CT in bowel and/or liver or spleen. PET2 agreement amongst experts (140 scans) with kappa (95% CI) of 0.84 (0.76 - 0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust enabling translation of RATHL results into clinical practice.

Published
2016
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22. Precision medicine in diffuse large B-cell lymphoma: Hitting the target

Author

Vermaat, Joost, S., Pals, Steven, T., Younes, Anas, Dreyling, Martin, Fedrico, Massimo, Aurer, Igor, Radford, John, Kersten, Marie, Jose, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Pathology, and Clinical Haematology

Subjects
Cell Transformation, Neoplastic, Editorials, Genetic Predisposition to Disease, Humans, Lymphoma, Large B-Cell, Diffuse, Molecular Targeted Therapy, Precision Medicine, Hematology, Medicine (all), diffuse large B-cell lymphoma, treatment
Abstract

Pregledni rad o mogućnostima ciljane terapije difuznog B-velikostaničnog limfoma

Published
2015

23. A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia

Author

Hillmen, Peter, Cohen, Dena R., Cocks, Kim, Pettitt, Andrew, Sayala, Hazem A., Rawstron, Andy C., Kennedy, Daniel B., Fegan, Christopher, Milligan, Don W., Radford, John, Mercieca, Jane, Dearden, Claire, Ezekwisili, Raphael, Smith, Alexandra F., Brown, Julia, Booth, Gillian A., Varghese, Abraham M., and Pocock, Christopher

Subjects
Chronic lymphocytic leukaemia, Fludarabine, ResearchInstitutes_Networks_Beacons/global_development_institute, Global Development Institute, immune system diseases, hemic and lymphatic diseases, Minimal residual disease, Phase II study, Mitoxantrone, Rituximab, Cyclophosphamide
Abstract

Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2months after therapy, with MRD negativity defined as

Published
2011
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24. Phase II trial of zanolimumab (HuMax-CD4) in relapsed or refractory non-cutaneous peripheral T-cell lymphoma

Author

D'Amore, Francesco, Radford, John, Relander, Thomas, Jerkeman, Mats, Tilly, Herve, Osterborg, Anders, Morschhauser, Franck, Gramatzki, Martin, Dreyling, Martin, Bang, Bo, Hagberg, Hans, Department of Hematology, Aarhus University Hospital, The Christie NHS Foundation Trust and The University of Manchester, Department of Oncology, Lund University Hospital, Department of Haematology, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Karolinska University Hospital [Stockholm], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille, 2nd Medical Department, University Hospital Schleswig-Holstein Campus Kiel, Division of Stem Cell Transplantation and, Department of Medicine III, University of Munich, Department of Dermatology, Bispebjerg Hospital, Department of Oncology, Radiology and Clinical Immunology, Section of Oncology, and Uppsala University Hospital

Subjects
Adult, Aged, 80 and over, Male, Antibodies, Monoclonal, Lymphoma, T-Cell, Peripheral, Antineoplastic Agents, Middle Aged, Opportunistic Infections, Treatment Outcome, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Female, Prospective Studies, Infusions, Intravenous, Aged
Abstract

International audience; Purpose To explore efficacy and safety of zanolimumab (HuMax-CD4) in patients with relapsed or refractory peripheral T cell lymphoma (PTCL). Patients and Methods Twenty-one adult patients with relapsed or refractory CD4+ PTCL of non-cutaneous type (angioimmunoblastic T-cell lymphoma (AITL) n=9, PTCL-not otherwise specified (NOS) n=7, anaplastic large cell lymphoma (ALCL) n=4 and enteropathy type T-cell lymphoma n=1) were treated in a single-arm multi-center study, with weekly intravenous infusions of zanolimumab 980 mg for 12 weeks. Median age was 69 years (range 26-85). Seventeen of the patients had advanced stage disease (Ann Arbor stages III-IV). Results Objective tumor responses were obtained in 24% of the patients with 2 complete responses unconfirmed (CRu) and 3 partial responses (PR). One of the CRus lasted more than 252 days. Responses were obtained in different PTCL entities: AITL (n=3), ALCL (n=1) and PTCL-NOS (n=1). In general, the trial drug was well tolerated with no major toxicity. No infections related to the trial drug were reported. Conclusion Zanolimumab at a dose of 980 mg weekly demonstrated clinical activity and an acceptable safety profile in this poor-prognosis patient population, suggesting that the potential benefit combining zanolimumab with standard chemotherapy in the treatment of PTCL should be investigated.

Published
2010
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25. First human exposure of Ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: Results of a phase I/II trial

Author

Hagenbeek, Anton, Plesner, Torben, Johnson, Peter, Pedersen, Lars Møller, Walewski, Jan, Hellmann, Andrzej, Link, Brian K., Wojtukiewicz, Marek, Pfeundschuh, Michael, Kneba, Michael, Engert, Andreas, Sonnenveld, Pieter, Radford, John A., Flensburg, Mimi Folden, Petersen, Jørgen, Losic, Nedjad, and Robak, Tadeusz

Abstract

Udgivelsesdato: 2008

Published
2008

27. Decanter

Author

Radford, John.

Subjects
Vinos España 2001 Artículos periodísticos, Vinos La Rioja 2001 Artículos periodísticos
Published
2001

28. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma (vol 378, pg 331, 2018)

Author

Connors, Joseph M., Jurczak, Wojciech, Straus, David J., Ansell, Stephen M., Kim, Won S., Gallamini, Andrea, Younes, Anas, Alekseev, Sergey, Illes, Arpad, Picardi, Marco, Ewa Lech-Maranda, Oki, Yasuhiro, Feldman, Tatyana, Smolewski, Piotr, Savage, Kerry J., Bartlett, Nancy L., Walewski, Jan, Chen, Robert, Ramchandren, Radhakrishnan, Zinzani, Pier L., Cunningham, David, Rosta, Andras, Josephson, Neil C., Song, Eric, Sachs, Jessica, Liu, Rachael, Jolin, Hina A., Huebner, Dirk, and Radford, John

29. Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

Author

Morschhauser, Franck, Dyer, Martin JS, Walter, Harriet S, Danilov, Alexey V, Ysebaert, Loic, Hodson, Daniel James, Fegan, Christopher, Rule, Simon A, Radford, John, Cartron, Guillaume, Bouabdallah, Krimo, Davies, Andrew John, Spurgeon, Stephen, Rajakumaraswamy, Nishanthan, Li, Biao, Humeniuk, Rita, Huang, Xi, Bhargava, Pankaj, Jürgensmeier, Juliane M, and Salles, Gilles

Subjects
Adult, Male, Indazoles, Lymphoma, B-Cell, Imidazoles, Antineoplastic Agents, Middle Aged, 3. Good health, Pyrimidines, immune system diseases, Purines, hemic and lymphatic diseases, Pyrazines, Humans, Female, Protein Kinase Inhibitors, Aged, Quinazolinones
Abstract

B-cell receptor (BCR) signaling pathway inhibitors (including Bruton’s tyrosine kinase [BTK] inhibitors, and phosphatidylinositol-3 kinase inhibitors [PI3Ki]) have shown clinical efficacy in non-Hodgkin lymphoma (NHL). However, responses to these agents have been limited in depth and duration. This may be due to resistance to PI3Kδ and BTK inhibitors as monotherapy. The emergence of resistant clones may be addressed by combining these 2 classes of drugs. Furthermore, tolerability of these drug classes has been a concern. Combination therapy using lower doses of one or more classes of inhibitor may address some limitations.

30. Phase 1b study of tirabrutinib in combination with idelalisib or entospletinib in previously treated B-cell lymphoma

Author

Morschhauser, Franck, Dyer, Martin J. S., Walter, Harriet S., Danilov, Alexey V., Ysebaert, Loic, Hodson, Daniel James, Fegan, Christopher, Rule, Simon A., Radford, John, Cartron, Guillaume, Bouabdallah, Krimo, Davies, Andrew John, Spurgeon, Stephen, Rajakumaraswamy, Nishanthan, Li, Biao, Humeniuk, Rita, Huang, Xi, Bhargava, Pankaj, Jürgensmeier, Juliane M., and Salles, Gilles

Subjects
Letter, 692/699/67/1059, 692/308/153, 3. Good health
Abstract

Funder: Gilead Sciences (Gilead); doi: https://doi.org/10.13039/100005564

31. Clinical Outcomes of Patients with Anaplastic Large Cell Lymphoma, Anaplastic Lymphoma Kinase-Negative (ALCL, ALK-): Analysis of 203 Patients Prospectively Registered in the International T-Cell Project

Author

Shustov, Andrei, Cabrera, Maria Elena, Bellei, Monica, Ko, Young Hyeh, Manni, Martina, Horwitz, Steven M., Souza, Carmino Antonio, Radford, John A., Varela, Sabela Bobillo, Prates, Maria Virginia, Ferreri, Andres J. M., Chiattone, Carlos, Michele Spina, Vose, Julie M., Chiappella, Annalisa, Laszlo, Daniele, Marino, Dario, Stelitano, Caterina, and Federico, Massimo

32. Pembrolizumab monotherapy in patients with primary refractory classical hodgkin lymphoma who relapsed after salvage autologous stem cell transplantation and/or brentuximab vedotin therapy: KEYNOTE-087 subgroup analysis

Author

Margaret A. Shipp, Bastian von Tresckow, Pier Luigi Zinzani, Akihiro Tomita, Robert T. Chen, Vincent Ribrag, Nathalie A. Johnson, Akash Nahar, Arun Balakumaran, John Radford, Theodoros P. Vassilakopoulos, Philippe Armand, Daniel Molin, Craig H. Moskowitz, Jianxin Lin, Pauline Brice, Zinzani, Pier Luigi, Chen, Robert, Armand, Philippe, Johnson, Nathalie A, Brice, Pauline, Radford, John, Ribrag, Vincent, Molin, Daniel, Vassilakopoulos, Theodoros P, Tomita, Akihiro, von Tresckow, Bastian, Shipp, Margaret A, Lin, Jianxin, Nahar, Akash, Balakumaran, Arun, and Moskowitz, Craig H

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Immunoconjugates, medicine.medical_treatment, Subgroup analysis, macromolecular substances, Pembrolizumab, Antibodies, Monoclonal, Humanized, Transplantation, Autologous, Article, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Refractory, immune system diseases, hemic and lymphatic diseases, Internal medicine, polycyclic compounds, Classical Hodgkin lymphoma, medicine, Humans, Brentuximab vedotin, Brentuximab Vedotin, Salvage Therapy, Chemotherapy, business.industry, Hematopoietic Stem Cell Transplantation, food and beverages, Hematology, Hodgkin Disease, 030220 oncology & carcinogenesis, Pembrolizumab, hodgkin lymphoma, autologous stem cell transplantation, brentuximab vedotin, Neoplasm Recurrence, Local, business, Chemoradiotherapy, Stem Cell Transplantation, 030215 immunology, medicine.drug
Abstract

Patients with classical Hodgkin lymphoma (cHL) typically receive first-line chemotherapy or chemoradiotherapy, and cure rates are high [1]. However, some patients may have primary refractory cHL, c...

Published
2020

33. Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087

Author

Pier Luigi Zinzani, Robert T. Chen, Akihiro Tomita, Vincent Ribrag, Pauline Brice, Theodoros P. Vassilakopoulos, Daniel Molin, Margaret A. Shipp, Craig H. Moskowitz, Arun Balakumaran, Nathalie A. Johnson, Bastian von Tresckow, Hun Ju Lee, Philippe Armand, John Radford, Eunhee Kim, Jianxin Lin, Akash Nahar, Chen, Robert, Zinzani, Pier Luigi, Lee, Hun Ju, Armand, Philippe, Johnson, Nathalie A, Brice, Pauline, Radford, John, Ribrag, Vincent, Molin, Daniel, Vassilakopoulos, Theodoros P, Tomita, Akihiro, von Tresckow, Bastian, Shipp, Margaret A, Lin, Jianxin, Kim, Eunhee, Nahar, Akash, Balakumaran, Arun, and Moskowitz, Craig H

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Adolescent, Immunology, Pembrolizumab, Antibodies, Monoclonal, Humanized, Biochemistry, Gastroenterology, Disease-Free Survival, Pembrolizumab, relapsed, refractory, Hodgkin lymphoma, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Autologous stem-cell transplantation, Antineoplastic Agents, Immunological, Refractory, Internal medicine, medicine, Refractory Hodgkin Lymphoma, Humans, Adverse effect, Brentuximab vedotin, Aged, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Cell Biology, Hematology, Middle Aged, medicine.disease, Hodgkin Disease, 030104 developmental biology, Treatment Outcome, Cohort, Female, Neoplasm Recurrence, Local, business, Progressive disease, 030215 immunology, medicine.drug, Follow-Up Studies
Abstract

Programmed death-1 inhibitors are approved for patients with relapsed or refractory classic Hodgkin lymphoma (RRcHL). We present the 2-year follow-up of the phase 2 KEYNOTE-087 study of pembrolizumab in 210 patients, based on HL progression after autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV; cohort 1); salvage chemotherapy and BV, with ineligibility for SCT owing to chemorefractory disease (cohort 2); and progression after SCT without BV (cohort 3). With a median follow-up of 27.6 months, the objective response rate (ORR) by blinded independent central review was 71.9% (95% CI, 65.3-77.9), the complete response rate (CRR) was 27.6%, and the partial response (PR) rate was 44.3%. Median duration of response was 16.5 months (range, 0.01 to 27.01 [1, no progressive disease at last assessment]) in all patients, 22.1 months in cohort 1, 11.1 months in cohort 2, and 24.4 months in cohort 3. Median progression-free survival was not reached in all patients with CR: 13.8 months (95% CI, 12.0-22.1) for patients with PR and 10.9 months (95% CI, 5.6-11.1) for patients with stable disease. Median overall survival was not reached in all patients or in any cohort. Treatment-related adverse events (TRAEs) of any grade occurred in 153 (72.9%) patients; grades 3 and 4 occurred in 25 (12.0%) patients; none resulted in death. Results confirmed effective antitumor activity, durability of response, and manageable safety of pembrolizumab monotherapy in RRcHL, regardless of prior treatment and including chemoresistant cHL. This trial was registered at www.clinicaltrials.gov as #NCT02453594.

Published
2019
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34. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma

Author

Yinghua Zhang, Michelle A. Fanale, Margaret A. Shipp, Akihiro Tomita, Vincent Ribrag, Philippe Armand, Daniel Molin, Arun Balakumaran, Craig H. Moskowitz, Robert W. Chen, Bastian von Tresckow, Pauline Brice, Nathalie A. Johnson, Alejandro D. Ricart, Pier Luigi Zinzani, John Radford, Theodoros P. Vassilakopoulos, Chen, Robert, Zinzani, Pier Luigi, Fanale, Michelle A, Armand, Philippe, Johnson, Nathalie A, Brice, Pauline, Radford, John, Ribrag, Vincent, Molin, Daniel, Vassilakopoulos, Theodoros P, Tomita, Akihiro, von Tresckow, Bastian, Shipp, Margaret A, Zhang, Yinghua, Ricart, Alejandro D, Balakumaran, Arun, and Moskowitz, Craig H

Subjects
Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Phases of clinical research, Antineoplastic Agents, Pembrolizumab, Antibodies, Monoclonal, Humanized, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, Recurrence, Internal medicine, Refractory Hodgkin Lymphoma, Humans, Medicine, Brentuximab vedotin, Aged, Manchester Cancer Research Centre, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, ORIGINAL REPORTS, Middle Aged, Hodgkin Disease, Surgery, Transplantation, 030104 developmental biology, 030220 oncology & carcinogenesis, 9p24, hodgkin, Cohort, Female, business, medicine.drug, Cohort study
Abstract

Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1–blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( ClinicalTrials.gov identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

Published
2017
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35. European phase II study of mogamulizumab, an anti-CCR4 monoclonal antibody, in relapsed/refractory peripheral T-cell lymphoma

Author

Pier Luigi Zinzani, Thomas Ng, Martine E D Chamuleau, Karen Dwyer, Franck Morschhauser, Eva González-Barca, Catherine Thieblemont, John Radford, Lionel Karlin, Francesco d'Amore, Dolores Caballero, Carlos Grande García, Gustaaf W. van Imhoff, Paul Fields, Peter Johnson, Corinne Haioun, Hematology, CCA - Clinical Therapy Development, Zinzani, PIER LUIGI, Karlin, Lionel, Radford, John, Caballero, Dolore, Fields, Paul, Chamuleau, Martine E. D., D’Amore, Francesco, Haioun, Corinne, Thieblemont, Catherine, González Barca, Eva, Grande García, Carlo, Johnson, Peter W., Van Imhoff, Gustaaf W., Thomas, Ng, Dwyer, Karen, Morschhauser, Franck, Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)

Subjects
0301 basic medicine, Oncology, Limfomes, medicine.medical_specialty, T cells, Phases of clinical research, Aggressive Non-Hodgkin Lymphoma, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Mogamulizumab, Medicine, CCL17, Online Only Articles, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Survival rate, anti-CCR4 monoclonal antibody, peripheral T-cell lymphoma, aggressive non-Hodgkin lymphoma, business.industry, mogamulizumab, Hematology, medicine.disease, Peripheral T-cell lymphoma, Europe, 030104 developmental biology, Cèl·lules T, 030220 oncology & carcinogenesis, Monoclonal, Immunology, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Lymphomas, Europa, business, CC chemokine receptors, medicine.drug
Abstract

CC chemokine receptor 4 (CCR4), the receptor for macrophage-derived chemokine (MDC/CCL22) and thymus activation-regulated chemokine (TARC/CCL17), is expressed on tumor cells in approximately 30-65% of patients with peripheral T-cell lymphoma (PTCL).1 Mogamulizumab, a defucosylated, humanized, IgG1 monoclonal antibody directed against CCR4 has been approved in Japan for the treatment of CCR4-positive relapsed/refractory PTCL. Mogamulizumab demonstrated effectiveness [overall response rate (ORR) 34%] in a phase II study of 29 Japanese patients with relapsed CCR4-positive PTCL.2 We conducted a phase II study in patients with relapsed or refractory CCR4-positive PTCL at 15 European centers (clinicaltrials.gov identifier :01611142). All patients gave written informed consent prior to enrollment. The study was conducted in accordance with the Declaration of Helsinki and in compliance with Good Clinical Practice guidelines. The protocol was approved by the Ethics Committee at each participating institution. The primary objective was to determine the best ORR of mogamulizumab. Secondary objectives included the duration of response, progression-free survival (PFS), and overall survival (OS) as well as the safety and immunogenicity of mogamulizumab.

Published
2016
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