P J Bröckelmann1, H Müller1, O Casasnovas2, M Hutchings3, B von Tresckow1, M Jürgens3, S J McCall4, F Morschhauser5, M Fuchs1, P Borchmann1, C H Moskowitz4, A Engert1. 1. Department I of Internal Medicine and German Hodgkin Study Group (GHSG), University Hospital of Cologne, Cologne, Germany. 2. Department of Hematology and Lymphoma Study Association (LYSA), Hopital Le Bocage, CHU Dijon, Dijon, France. 3. Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark. 4. Memorial Sloan Kettering Cancer Center (MSKCC), New York City, USA. 5. Department of Hematology, Unité GRITA, Université de Lille 2, Hopital Claude Huriez, Lille, France.
Abstract
BACKGROUND: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT. METHODS: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II). RESULTS: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [<partial remission by computed tomography (CT)] as significant and non-redundant RFs for PFS. A risk score composed of these equally weighed RFs was significantly prognostic for PFS (HR = 1.67 for each additional RF; P < 0.0001). Validation in an independent sample of 389 patients treated in different clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellent discrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR = 1.70 and HR = 1.63, respectively; P < 0.0001). CONCLUSIONS: Based on this large study (n = 1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials. REGISTERED TRIALS: GHSG HD10 NCT00265018, HD11 NCT00264953, HD12 NCT00265031, HD13 ISRCTN63474366, HD14 ISRCTN04761296, HD15 ISRCTN32443041 and HDR2 NCT00025636.
BACKGROUND: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT. METHODS: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I). The resulting prognostic score was then validated in an independent clinical sample (part II). RESULTS: In part I, we identified 656 patients treated for relapsed/refractory HL between 1993 and 2013 with a median follow-up of 60 months after ASCT. The majority of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [<partial remission by computed tomography (CT)] as significant and non-redundant RFs for PFS. A risk score composed of these equally weighed RFs was significantly prognostic for PFS (HR = 1.67 for each additional RF; P < 0.0001). Validation in an independent sample of 389 patients treated in different clinical settings with evaluation of response to salvage therapy by functional imaging instead of CT confirmed the excellent discrimination of risk groups and significant prognostication of PFS and overall survival (OS) after ASCT (HR = 1.70 and HR = 1.63, respectively; P < 0.0001). CONCLUSIONS: Based on this large study (n = 1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials. REGISTERED TRIALS: GHSG HD10 NCT00265018, HD11 NCT00264953, HD12 NCT00265031, HD13 ISRCTN63474366, HD14 ISRCTN04761296, HD15 ISRCTN32443041 and HDR2 NCT00025636.
Authors: Lisa Giulino-Roth; Tara O'Donohue; Zhengming Chen; Tanya M Trippett; Elizabeth Klein; Nancy A Kernan; Rachel Kobos; Susan E Prockop; Andromachi Scaradavou; Neerav Shukla; Peter G Steinherz; Alison J Moskowitz; Craig H Moskowitz; Farid Boulad Journal: Leuk Lymphoma Date: 2017-11-29
Authors: Tim M Illidge; Elizabeth H Phillips; Nicholas Counsell; Ruth Pettengell; Peter W M Johnson; Dominic J Culligan; Bilyana Popova; Laura Clifton-Hadley; Andrew McMillan; Peter Hoskin; Sally F Barrington; John Radford Journal: Blood Adv Date: 2020-01-14
Authors: Alison J Moskowitz; Heiko Schöder; Somali Gavane; Katie L Thoren; Martin Fleisher; Joachim Yahalom; Susan J McCall; Briana R Cadzin; Stephanie Y Fox; John Gerecitano; Ravinder Grewal; Paul A Hamlin; Steven M Horwitz; Anita Kumar; Matthew Matasar; Andy Ni; Ariela Noy; M Lia Palomba; Miguel-Angel Perales; Carol S Portlock; Craig Sauter; David Straus; Anas Younes; Andrew D Zelenetz; Craig H Moskowitz Journal: Blood Date: 2017-09-05 Impact factor: 22.113
Authors: Joseph M Connors; Wendy Cozen; Christian Steidl; Antonino Carbone; Richard T Hoppe; Hans-Henning Flechtner; Nancy L Bartlett Journal: Nat Rev Dis Primers Date: 2020-07-23 Impact factor: 52.329
Authors: Yago Nieto; Peter F Thall; Junsheng Ma; Benigno C Valdez; Sairah Ahmed; Paolo Anderlini; Uday Popat; Roy B Jones; Elizabeth J Shpall; Chitra Hosing; Muzaffar Qazilbash; Partow Kebriaei; Amin Alousi; Melissa Timmons; Alison Gulbis; Alan Myers; Yasuhiro Oki; Michelle Fanale; Bouthaina Dabaja; Chelsea Pinnix; Sarah Milgrom; Richard Champlin; Borje S Andersson Journal: Biol Blood Marrow Transplant Date: 2018-03-02 Impact factor: 5.742
Authors: S M Hiniker; R T Hoppe; M L Dworkin; A L Jiang; R Von Eyben; M A Spinner; R H Advani; R Lowsky Journal: Bone Marrow Transplant Date: 2021-10-20 Impact factor: 5.483
Authors: Paul J Bröckelmann; Dennis A Eichenauer; Tina Jakob; Markus Follmann; Andreas Engert; Nicole Skoetz Journal: Dtsch Arztebl Int Date: 2018-08-06 Impact factor: 5.594
Authors: Emma Das-Gupta; Kirsty J Thomson; Adrian J C Bloor; Andrew D Clark; Stephen Mackinnon; Irfan Kayani; Laura Clifton-Hadley; Pip Patrick; Nadjet El-Mehidi; Anthony Lawrie; Amy A Kirkwood; Nigel H Russell; David C Linch; Karl S Peggs Journal: Blood Adv Date: 2019-12-23