Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry

Abstract

This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing DLBCL; after several patients with little to no CD30 achieved a complete remission (CR), the study evaluated treatment of DLBCL with undetectable CD30 (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL patients (31%) had an objective response (6 CRs [12%]). Median progression-free survival (PFS) was 1.4 months (range, 0.4–15.6) and median overall survival (OS) was 7.5 months (range, 0.7–18.6+). Subsequent CD30 expression quantitated by computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL responders had ≥1% CD30. Correlative analyses of CD30u and CD30-expressing DLBCL combined demonstrated that ≥1% CD30 expression by cIHC resulted in a trend toward a higher response rate and significantly longer median PFS and OS. A minimum CD30 expression threshold appears to be required for antitumor activity in DLBCL; however, other factors also likely contribute to activity. (NCT01421667).

Keywords:

• DLBCL
• antibody-based immunotherapy
• lymphoma
• immunotherapy
• antibody-drug conjugate

Acknowledgements

The authors wish to acknowledge Tiffany Griffin for medical writing assistance, as a contract employee of Seattle Genetics, Inc., and Shawna Hengel, an employee of Seattle Genetics, for assessment of tumor monomethyl auristatin E (MMAE) on optional biopsies. Seattle Genetics, Inc. authors, M. C. Palanca-Wessels, M. Uttarwar, M. Li, and J. Yang, participated in development of the study design; collection, analysis, and interpretation of data; report writing; and in the decision to submit the paper for publication. Seattle Genetics, Inc. provided research funding to the institutions of N. L. Bartlett, M. R. Smith, T. Siddiqi, R. H. Advani, O. A. O’Connor, J. P. Sharman, T. Feldman, K. J. Savage, A. R. Shustov, C. S. Diefenbach, Y. Oki, and E. D. Jacobsen.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.1080/10428194.2016.1256481.