Dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide as salvage therapy for patients with diffuse large B-cell lymphoma relapsing after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone: a randomized, double-blind, placebo-controlled phase 2b trial

Abstract

Single-agent dacetuzumab has demonstrated antitumor activity in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Preclinical data demonstrated improved dacetuzumab antitumor activity in combination with rituximab, ± chemotherapy. We designed a phase 2b, double-blind, placebo-controlled trial to compare rituximab, ifosfamide, carboplatin and etoposide (R-ICE) + dacetuzumab with R-ICE + placebo in patients with DLBCL who relapsed after rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) (ClinicalTrials.gov #NCT00529503). The primary endpoint was complete response (CR); additional endpoints included failure-free survival and overall survival (OS). Overall, 151 patients were randomized (75 dacetuzumab, 76 placebo). No notable differences between arms in demographics or subsequent treatment parameters were observed. Cytopenias, cough and infection were more frequent with dacetuzumab. Futility analysis failed to demonstrate higher CR rates with dacetuzumab (36% dacetuzumab, 42% placebo); consequently, enrollment was stopped. Unplanned post hoc analysis showed that patients who underwent subsequent autologous stem cell transplant experienced improvement in OS (hazard ratio = 0.195, p = 0.004), which may be explained by potential immunomodulatory effects of dacetuzumab on antigen-presenting cells.

Keywords::

• Dacetuzumab
• diffuse large B-cell lymphoma
• R-ICE
• stem cell transplant
• salvage therapy

Acknowledgments

The authors thank the patients who participated in this study and their families, and would like to thank the members of the IDMC, including Joseph M. Connors, Alan K. Burnett, Jerald P. Radich, Claudio Anasetti and Daniel L. Gillen. The authors also thank Natalie Masterton of Seattle Genetics, Inc. for her project management support and Tiffany Griffin of Seattle Genetics, Inc. for her writing support.

This work was supported by research funding from Seattle Genetics, Inc. and Genentech, Inc. for all authors and sites listed in the Supplementary Material. to be found online at http://informahealthcare.com/doi/abs/10.3109/10428194.2015.1007504

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

Supplementary material available online

Supplementary Material, Additional methods and results and list of contributors