Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study

Abstract

This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. Trial Registration: ClinicalTrials.gov identifier: NCT02686346

Keywords:

• Hodgkin lymphoma
• relapse
• refractory
• salvage chemotherapy
• brentuximab vedotin
• ICE regimen
• autologous stem cell transplantation

Acknowledgments

The authors would like to thank all patients who participated in this trial and their families, as well as investigators and staff of all clinical sites. All LYSARC members for their assistance. The study drug (BV) was provided for the study and the study was funded by Takeda.

Authors contributions

PB and VR designed the study; all authors collected the data; AS and PB analyzed the data; wrote the manuscript with contributions from all authors, who also read, commented on, and approved the final version of the manuscript; ABR, TVB and VE performed the central PET-CT review; AS and PB supervised the study.

Disclosure statement

A Stamatoullas: Honoraria: Janssen, Pfizer; Travel Grants: Pfizer, Roche, Abbevie

H Ghesquieres: Consultancy: Gilead Sciences, Celgene, Roche; Honoraria: Gilead Sciences, Janssen, Celgene; Travel expenses: Roche, Gilead Sceinces, Celgene, Takeda

P Feugier: Advisory Board and Travel Grants : Roche, AstraZeneca, Janssen, Abbvie, Amgen

M André: Advisory Board: Takeda, BMS, Karyopharm, Gilead, Incyte; Research Grants: Roche, Johnson & Johnson, Takeda; Travel Grants: Roche, BMS, Celgene, Gilead, Abbvie

T Gastinne: Honoraria: Millenium/Takeda, Gilead, Roche, Janssen

F Morschhauser: Board of Directors or Advisory committees: BMS, Roche, Celgene, Gilead; Scientific lectures: Janssen; Consultancy: Epizyme, Gilead, Celgene

V Ribrag: Research funding: Astex, consultancy: servier; Scientific Advisory Board: Nanostring, Gilead, BMS, MSD, Incyte, Roche, Infinity, AZ.

S Guidez: Advisory Board: Takeda and Janssen; Scientific lectures: Sanofi

P Brice: Research support/PI: Millenium Pharmaceuticals, Inc, AMGEN, Takeda; Honoraria: Takeda, Roche, BMS, MSD, Jansen; Scientific Advisory Board: Takeda, BMS, MSD

All other authors have declared no conflicts of interest.

Fund ing

This work was supported by Takeda Development Center Americas, Inc.