Treatment pathways and clinical outcomes in Hodgkin lymphoma outside Europe and North America: results from the international, multicenter, retrospective, B-HOLISTIC study

Abstract

Information on Hodgkin lymphoma (HL) is mostly limited to Europe and North America. This real-world, retrospective study assessed treatment pathways and clinical outcomes in adults with stage IIB–IV classical HL receiving frontline treatment (n = 1598) or relapsed/refractory HL (RRHL, n = 426) in regions outside Europe and North America between January 2010 and December 2013. The primary endpoint was progression-free survival (PFS) in the RRHL group. Among patients with RRHL, 89.0% received salvage chemotherapy; most common regimen was etoposide, methylprednisolone, cytarabine, cisplatin (ESHAP; 26.3%). Median PFS in the RRHL group was 13.2 months (95% confidence interval [CI]: 9.9–20.2) and was longer in patients with vs. without stem cell transplantation (SCT; 20.6 vs. 7.5 months; p = 0.0071). This large-scale study identified a lower PFS for RRHL in the rest of the world compared with Europe and North America, highlighting the need for novel targeted therapies and SCT earlier in the treatment continuum.

Clinical trial registration: NCT03327571.

Keywords:

• Hodgkin lymphoma
• relapsed/refractory
• treatment outcome
• developing country
• real-world evidence

Acknowledgments

The authors would like to thank all patients, participating principal and co-investigators, and study-site staff for their contributions to the B-HOLISTIC study, with special mention to the principal investigators from the participating centers: Saad Akhtar, King Faisal Specialist Hospital and Research Center, Saudi Arabia; Sevgi Besisik, Istanbul University Medical Faculty, Turkey; Alvaro Hernandez, Unidad Médica de Alta Especialidad, Dr. Antonio Fraga Mouret, Centro Médico La Raza, IMSS, Mexico; Muhit Ozcan, Ankara University Medical Faculty, Turkey; Irina Kryuchkova, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Russia; Can Boga, Baskent University Adana Application and Research Center, Turkey; Mehmet Turgut, Ondokuz Mayis University Medical Faculty, Turkey; Mohsen Al Zahrani, National Guard Hospital–King Abdulaziz Medical City, Saudi Arabia; Dorotea Fantl, Hospital Italiano de Buenos Aires, Argentina; Ruben Salazar, Clinica De Oncologia Astorga, Colombia; Chien-Yuan Chen, National Taiwan University Hospital, Taiwan; Kenny Galvez, Hospital Pablo Tobón Uribe, Colombia; Moosa Patel, Chris Hani Baragwanath Hospital, South Africa; Seok-Goo Cho, The Catholic University of Korea, Seoul St. Mary’s Hospital, South Korea; and Juan Antonio Flores Jimenez, Centro de Investigación Farmacéutica Especializada de Occidente, S.C, Mexico. We would also like to acknowledge the continuous support of Frances Quek, who was the Clinical Study Manager at Takeda Pharmaceuticals during the time of this study. Data analysis was provided by IQVIA, and editorial assistance was provided by Brad Dalton BAppSc, MSc, and Sandra Kurian, MPharm, of Synergy Vision Ltd (London, UK), with funding from Takeda Pharmaceuticals International AG–Singapore Branch.

Author contributions

All authors had access to and verified all the data reported in this manuscript and accept responsibility for this publication. All authors were involved in study design, methodology, data collection, and contributed equally toward analysis, interpretation of results, and manuscript development. All authors have reviewed and approved this manuscript for publication.

Disclosure statement

Burhan Ferhanoglu serves as a member of a board of directors or advisory committee of Takeda, Roche, AbbVie, and Janssen. Tae Min Kim has consulting and advisory roles for AstraZeneca, Boryung, Hanmi, Novartis, Takeda, Sanofi, and Roche/Genentech; receives a grant from AstraZeneca-KHIDI outside this work; and has received consulting fees from AstraZeneca, Hanmi, Novartis, and Takeda. Amado Karduss has received honoraria from Takeda, Amgen, and Janssen, and serves as a member of a board of directors or advisory committee of Novartis. David Brittain has received honoraria from Takeda, Roche, AbbVie, and Janssen, and serves as a member of a board of directors or advisory committee for Takeda. Gayane Tumyan and Mubarak Al-mansour serve as members of a board of directors or advisory committee for Takeda. Marta Zerga has received conference fees from Bristol Myers Squibb, Janssen, Roche, and Takeda; has received support for attending meetings from Sandoz, Amgen, AbbVie, Teva, and Pint Pharma; has received honoraria from Takeda, AbbVie, AstraZeneca, Teva, and Sandoz; and has participated on the advisory board for Takeda, Janssen, and Merck. Yuqin Song has received conference fees from Takeda and has participated on the advisory boards for Roche, Takeda, and Janssen. Silvia Rivas-Vera has received honoraria from Roche and serves on the advisory board for Takeda. Yok Lam Kwong serves as a consultant and has received honoraria or research funding from Amgen, Astellas, Bayer, BeiGene, Bristol Myers Squibb, Celgene, Gilead, Janssen, Merck, Novartis, Roche, and Takeda. Soon Thye Lim's institution has received honoraria from Takeda. Su-Peng Yeh has received honoraria from AbbVie, Amgen, Janssen, Astellas, AstraZeneca, Novartis, Sanofi, Roche, Bristol Myers Squibb, and Takeda, and has served in an advisory role for AbbVie, Amgen, Janssen, Astellas, Astex, Novartis, Sanofi, and Takeda. Arif Abdillah was an employee of Takeda Pharmaceuticals during the time of this study and is currently affiliated with GlaxoSmithKline Pte Limited. Zhongwen Huang is an employee of Takeda Pharmaceuticals and holds shares in the company. Hui Wan was an employee of Takeda Pharmaceuticals at the time of the study and is currently employed with Cellular Biomedicine Group. Mehul Dalal is an employee of Takeda Pharmaceuticals and owns equity in the company. Mark Hertzberg has received honoraria, consulting fees, and serves as a member of a board of directors or advisory committee of Takeda, Roche, BMS, Gilead, and MSD.

Data availability statement

The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual participants’ data supporting the results reported in this article will be made available within 3 months from the initial request to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protection, and requirements for consent and anonymization.

Additional information

Funding

This study was funded by Takeda Pharmaceuticals International AG–Singapore Branch.