Nicole A Carreau1, Orrin Pail2, Philippe Armand3, Reid Merryman3, Ranjana H Advani4, Michael A Spinner4, Alex Herrera5, Robert Chen5, Sarah Tomassetti5, Radhakrishnan Ramchandren6, Muhammad S Hamid7, Sarit Assouline8, Raoul Santiago8, Nina Wagner-Johnston9, Suman Paul9, Jakub Svoboda10, Steven Bair10, Stefan Barta10, Yang Liu11, Sunita Nathan12, Reem Karmali13, Madelyn Burkart13, Pallawi Torka14, Kevin David15, Catherine Wei15, Frederick Lansigan16, Lukas Emery16, Daniel Persky17, Sonali Smith18, James Godfrey18, Julio Chavez19, Yuhe Xia20, Andrea B Troxel20, Catherine Diefenbach1. 1. Division of Hematology and Medical Oncology, Perlmutter Cancer Center at NYU Langone Health, New York, New York, USA. 2. Department of Medicine, New York University School of Medicine & Langone Medical Center, New York, New York, USA. 3. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA. 4. Department of Medicine, Division of Oncology, Stanford University, Stanford, California, USA. 5. Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, California, USA. 6. Division of Hematology and Oncology, University of Tennessee Medical Center, Knoxville, Tennessee, USA. 7. Department of Oncology, Karmanos Cancer Institute, Detroit, Michigan, USA. 8. McGill University, Montreal, Quebec, Canada. 9. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA. 10. Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. 11. Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. 12. Rush University Medical Center, Chicago, Illinois, USA. 13. Division of Hematology, Northwestern University, Chicago, Illinois, USA. 14. Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA. 15. Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA. 16. Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA. 17. Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson, Arizona, USA. 18. University of Chicago, Chicago, Illinois, USA. 19. Moffitt Cancer Center, Tampa, Florida, USA. 20. New York University School of Medicine, New York, New York, USA.
Abstract
BACKGROUND: Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed and refractory (R/R) setting, but once discontinued owing to progression or side effects, it is unclear how successful further therapies will be. Moreover, there are no data on optimal sequencing of these treatments with standard therapies and other novel agents. In a multicenter, retrospective analysis, we investigated whether exposure to CBT could sensitize HL to subsequent therapy. MATERIALS AND METHODS: Seventeen centers across the U.S. and Canada retrospectively queried medical records for eligible patients. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment using the Lugano criteria. Secondary aims included progression-free survival (PFS), duration of response, and overall survival (OS). RESULTS: Eighty-one patients were included. Seventy-two percent had stage III-IV disease, and the population was heavily pretreated with a median of four therapies before CBT. Most patients (65%) discontinued CBT owing to progression. The ORR to post-CBT therapy was 62%, with a median PFS of 6.3 months and median OS of 21 months. Post-CBT treatment regimens consisted of chemotherapy (44%), targeted agents (19%), immunotherapy (15%), transplant conditioning (14%), chemotherapy/targeted combination (7%), and clinical trials (1%). No significant difference in OS was found when stratified by post-CBT regimen. CONCLUSION: In a heavily pretreated R/R HL population, CBT may sensitize patients to subsequent treatment, even after progression on CBT. Post-CBT regimen category did not impact OS. This may be a novel treatment strategy, which warrants further investigation in prospective clinical trials. IMPLICATIONS FOR PRACTICE: Novel, life-prolonging treatment strategies in relapsed and refractory (R/R) Hodgkin lymphoma (HL) are greatly desired. The results of this multicenter analysis concur with a smaller, earlier report that checkpoint blockade therapy (CBT) use in R/R HL may sensitize patients to their subsequent treatment. This approach may potentially enhance therapeutic options or to bridge patients to transplant. Prospective data are warranted prior to practice implementation. As more work is done in this area, we may also be able to optimize sequencing of CBT and novel agents in the treatment paradigm to minimize treatment-related toxicity and thus improve patient quality of life.
BACKGROUND: Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed and refractory (R/R) setting, but once discontinued owing to progression or side effects, it is unclear how successful further therapies will be. Moreover, there are no data on optimal sequencing of these treatments with standard therapies and other novel agents. In a multicenter, retrospective analysis, we investigated whether exposure to CBT could sensitize HL to subsequent therapy. MATERIALS AND METHODS: Seventeen centers across the U.S. and Canada retrospectively queried medical records for eligible patients. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment using the Lugano criteria. Secondary aims included progression-free survival (PFS), duration of response, and overall survival (OS). RESULTS: Eighty-one patients were included. Seventy-two percent had stage III-IV disease, and the population was heavily pretreated with a median of four therapies before CBT. Most patients (65%) discontinued CBT owing to progression. The ORR to post-CBT therapy was 62%, with a median PFS of 6.3 months and median OS of 21 months. Post-CBT treatment regimens consisted of chemotherapy (44%), targeted agents (19%), immunotherapy (15%), transplant conditioning (14%), chemotherapy/targeted combination (7%), and clinical trials (1%). No significant difference in OS was found when stratified by post-CBT regimen. CONCLUSION: In a heavily pretreated R/R HL population, CBT may sensitize patients to subsequent treatment, even after progression on CBT. Post-CBT regimen category did not impact OS. This may be a novel treatment strategy, which warrants further investigation in prospective clinical trials. IMPLICATIONS FOR PRACTICE: Novel, life-prolonging treatment strategies in relapsed and refractory (R/R) Hodgkin lymphoma (HL) are greatly desired. The results of this multicenter analysis concur with a smaller, earlier report that checkpoint blockade therapy (CBT) use in R/R HL may sensitize patients to their subsequent treatment. This approach may potentially enhance therapeutic options or to bridge patients to transplant. Prospective data are warranted prior to practice implementation. As more work is done in this area, we may also be able to optimize sequencing of CBT and novel agents in the treatment paradigm to minimize treatment-related toxicity and thus improve patient quality of life.
Authors: Mahmoud A Elshenawy; M Shahzad Rauf; Tusneem A M Elhassan; Irfan Maghfoor; Saad Akhtar Journal: Ann Hematol Date: 2018-02-26 Impact factor: 3.673
Authors: Brian I Rini; Elizabeth R Plimack; Viktor Stus; Rustem Gafanov; Robert Hawkins; Dmitry Nosov; Frédéric Pouliot; Boris Alekseev; Denis Soulières; Bohuslav Melichar; Ihor Vynnychenko; Anna Kryzhanivska; Igor Bondarenko; Sergio J Azevedo; Delphine Borchiellini; Cezary Szczylik; Maurice Markus; Raymond S McDermott; Jens Bedke; Sophie Tartas; Yen-Hwa Chang; Satoshi Tamada; Qiong Shou; Rodolfo F Perini; Mei Chen; Michael B Atkins; Thomas Powles Journal: N Engl J Med Date: 2019-02-16 Impact factor: 91.245
Authors: Nicole A Carreau; Philippe Armand; Reid W Merryman; Ranjana H Advani; Michael A Spinner; Alex F Herrera; Radhakrishnan Ramchandren; Muhammad S Hamid; Sarit Assouline; Raoul Santiago; Nina Wagner-Johnston; Suman Paul; Jakub Svoboda; Steven M Bair; Stefan K Barta; Sunita Nathan; Reem Karmali; Pallawi Torka; Kevin David; Frederick Lansigan; Daniel Persky; James Godfrey; Julio C Chavez; Yuhe Xia; Catherine Diefenbach Journal: Br J Haematol Date: 2020-05-19 Impact factor: 6.998
Authors: Talha Badar; Narendranath Epperla; Aniko Szabo; Steven Borson; John Vaughn; Gemlyn George; Neeraj Saini; Abdul Rashid Shah; Romil D Patel; Sairah Ahmed; Nirav N Shah; Amanda F Cashen; Mehdi Hamadani; Timothy S Fenske Journal: Blood Adv Date: 2020-01-14
Authors: Jonathan S Serody; Ivana Gojo; Joshua F Zeidner; Benjamin G Vincent; Anastasia Ivanova; Dominic Moore; Karen P McKinnon; Alec D Wilkinson; Rupkatha Mukhopadhyay; Francesco Mazziotta; Hanna A Knaus; Matthew C Foster; Catherine C Coombs; Katarzyna Jamieson; Hendrik Van Deventer; Jonathan A Webster; Gabrielle T Prince; Amy E DeZern; B Douglas Smith; Mark J Levis; Nathan D Montgomery; Leo Luznik Journal: Blood Cancer Discov Date: 2021-09-10
Authors: Reid W Merryman; Robert A Redd; Taiga Nishihori; Julio Chavez; Yago Nieto; Justin M Darrah; Uttam Rao; Michael T Byrne; David A Bond; Kami J Maddocks; Michael A Spinner; Ranjana H Advani; Hatcher J Ballard; Jakub Svoboda; Anurag K Singh; Joseph P McGuirk; Dipenkumar Modi; Radhakrishnan Ramchandren; Jason Romancik; Jonathon B Cohen; Matthew J Frigault; Yi-Bin Chen; Anthony V Serritella; Justine Kline; Stephen Ansell; Sunita Nathan; Maryam Rahimian; Robin M Joyce; Mansi Shah; Kevin A David; Steven Park; Anne W Beaven; Alma Habib; Veronika Bachanova; Shazia Nakhoda; Nadia Khan; Ryan C Lynch; Stephen D Smith; Vincent T Ho; Ann LaCasce; Philippe Armand; Alex F Herrera Journal: Blood Adv Date: 2021-03-23
Authors: Roch Houot; Viola Poeschel; Bettina Altmann; Stephanie Angel; Lorenz Thurner; Thomas Illmer; Marc Andre; Martin Dreyling; Hervé Maisonneuve; Hervé Tilly; Stephanie Mayer; Olivier Casasnovas; Steven Le Gouill; Fritz Offner; Guillaume Cartron; Andrea Kerkhoff; Thomas Weber; Joerg Hoffmann; Marita Ziepert; Wolfram Klapper; Emmanuel Itti; Dirk Hellwig; Giorgi Natchkebia; Laurence de Leval; Andreas Rosenwald; Corinne Haioun; Laurent Dercle; Philippe Gaulard; Gerhard Held Journal: Hemasphere Date: 2022-01-10