Real-world Retrospective Analysis of Immune Checkpoint Inhibitor Therapy for Relapsed or Refractory Hodgkin's Lymphoma

Overview

Journal J Clin Exp Hematop

Specialties Hematology
Pathology

Date 2024 Jul 31

PMID 39085129

Authors

Tatsuo Oyake

Takahiro Maeta

Takenori Takahata

Yoshiko Tamai

Yoshihiro Kameoka

Naoto Takahashi

Yasuro Miyairi

Kazunori Murai

Kenji Shimosegawa

Kozue Yoshida

Kyoko Inokura

Noriko Fukuhara

Hideo Harigae

Ryo Sato

Kenichi Ishizawa

Katsushi Tajima

Souichi Saitou

Masahiko Fukatsu

Takayuki Ikezoe

Saburo Tsunoda

Masayuki Mita

Jinichi Mori

Shugo Kowata

Shigeki Ito

Affiliations

Soon will be listed here.

Abstract

Immune checkpoint inhibitors (ICI) are promising therapeutic agents for relapsed or refractory classical Hodgkin's lymphoma (RRcHL). This retrospective study evaluated patients with RRcHL registered in the clinical research program Tohoku-Hematology-Forum-26, between 2016 and 2020, and treated with ICI in 14 centers in Northeast Japan. We analyzed the usage, efficacy, and safety of ICI therapy (ICIT). Among a total of 27 patients with RRcHL, 21 and nine were treated with nivolumab and/or pembrolizumab, respectively. The best response was complete response (CR), partial response (PR), stable disease (SD), and progressive disease in 11 (40.8%), seven (25.9%), eight (29.6%), and one (3.7%) patient, respectively. In all patients undergoing ICIT, the 2-year progression-free survival and 2-year overall survival (OS) were 48.6% and 87.4%, respectively. The 2-year OS for patients with CR, PR, and SD were 100%, 68.6%, and 87.5%, respectively. A total of 36 events of immune-related adverse events (irAEs) or immune-related like adverse events (irlAEs) were observed in 19 of the 27 patients (70.4%). Two thirds of these irAEs or irlAEs were grade 1-2 and controllable. During the observation period, ICIT was discontinued in 22 of 27 (81.4%) patients due to CR, inadequate response, irAE and patient circumstances in five (22.7%), seven (31.8%), eight (36.4%) and two patients (9.1%), respectively. Therapy-related mortality-associated irAE were observed in only one patient during ICIT. These results suggest that ICIT for RRcHL is effective and safe in real-world settings. The optimal timing of induction and duration of ICIT remains to be established.

References

Younes A, Santoro A, Shipp M, Zinzani P, Timmerman J, Ansell S . Nivolumab for classical Hodgkin's lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016; 17(9):1283-94. PMC: 5541855. DOI: 10.1016/S1470-2045(16)30167-X. View

Maruyama D, Hatake K, Kinoshita T, Fukuhara N, Choi I, Taniwaki M . Multicenter phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Cancer Sci. 2017; 108(5):1007-1012. PMC: 5448600. DOI: 10.1111/cas.13230. View

Makita S, Maruyama D, Maeshima A, Taniguchi H, Miyamoto K, Kitahara H . Clinical features and outcomes of 139 Japanese patients with Hodgkin lymphoma. Int J Hematol. 2016; 104(2):236-44. DOI: 10.1007/s12185-016-2007-1. View

Connors J, Jurczak W, Straus D, Ansell S, Kim W, Gallamini A . Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2017; 378(4):331-344. PMC: 5819601. DOI: 10.1056/NEJMoa1708984. View

Ansell S, Brockelmann P, von Keudell G, Lee H, Santoro A, Zinzani P . Nivolumab for relapsed/refractory classical Hodgkin lymphoma: 5-year survival from the pivotal phase 2 CheckMate 205 study. Blood Adv. 2023; 7(20):6266-6274. PMC: 10589773. DOI: 10.1182/bloodadvances.2023010334. View

Ogura M, Itoh K, Kinoshita T, Fukuda H, Takenaka T, Ohtsu T . Phase II study of ABVd therapy for newly diagnosed clinical stage II-IV Hodgkin lymphoma: Japan Clinical Oncology Group study (JCOG 9305). Int J Hematol. 2010; 92(5):713-24. DOI: 10.1007/s12185-010-0712-8. View

Bair S, Strelec L, Feldman T, Ahmed G, Armand P, Shah N . Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis. Oncologist. 2018; 24(7):955-962. PMC: 6656463. DOI: 10.1634/theoncologist.2018-0538. View

Chen R, Zinzani P, Fanale M, Armand P, Johnson N, Brice P . Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017; 35(19):2125-2132. PMC: 5791843. DOI: 10.1200/JCO.2016.72.1316. View

Yuen A, Rosenberg S, Hoppe R, Halpern J, Horning S . Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease. Blood. 1997; 89(3):814-22. View

10.

Schmitz N, Pfistner B, Sextro M, Sieber M, Carella A, Haenel M . Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002; 359(9323):2065-71. DOI: 10.1016/S0140-6736(02)08938-9. View

11.

Maruyama D, Terui Y, Yamamoto K, Fukuhara N, Choi I, Kuroda J . Final results of a phase II study of nivolumab in Japanese patients with relapsed or refractory classical Hodgkin lymphoma. Jpn J Clin Oncol. 2020; 50(11):1265-1273. PMC: 7579338. DOI: 10.1093/jjco/hyaa117. View

12.

Bekoz H, Ozbalak M, Karadurmus N, Paydas S, Turker A, Toptas T . Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience. Ann Hematol. 2020; 99(11):2565-2576. DOI: 10.1007/s00277-020-04077-4. View

13.

Nagai H . JSH practical guidelines for hematological malignancies, 2018: II. Lymphoma-10. Hodgkin lymphoma (HL). Int J Hematol. 2019; 111(2):166-179. DOI: 10.1007/s12185-019-02785-w. View

14.

. The world health organization classification of malignant lymphomas in japan: incidence of recently recognized entities. Lymphoma Study Group of Japanese Pathologists. Pathol Int. 2000; 50(9):696-702. DOI: 10.1046/j.1440-1827.2000.01108.x. View

15.

Chen R, Zinzani P, Lee H, Armand P, Johnson N, Brice P . Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087. Blood. 2019; 134(14):1144-1153. PMC: 6776792. DOI: 10.1182/blood.2019000324. View

16.

Linch D, Winfield D, Goldstone A, Moir D, Hancock B, McMillan A . Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial. Lancet. 1993; 341(8852):1051-4. DOI: 10.1016/0140-6736(93)92411-l. View

17.

Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani P . Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018; 36(14):1428-1439. PMC: 6075855. DOI: 10.1200/JCO.2017.76.0793. View

18.

Thompson J, Schneider B, Brahmer J, Andrews S, Armand P, Bhatia S . NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020. J Natl Compr Canc Netw. 2020; 18(3):230-241. DOI: 10.6004/jnccn.2020.0012. View

19.

Straus D, Dlugosz-Danecka M, Connors J, Alekseev S, Illes A, Picardi M . Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021; 8(6):e410-e421. DOI: 10.1016/S2352-3026(21)00102-2. View

20.

Cheson B, Pfistner B, Juweid M, Gascoyne R, Specht L, Horning S . Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25(5):579-86. DOI: 10.1200/JCO.2006.09.2403. View