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

Nancy L. Bartlett; Mitchell R. Smith; Tanya Siddiqi; Ranjana H. Advani; Owen A. O’Connor; Jeff P. Sharman; Tatyana Feldman; Kerry J. Savage; Andrei R. Shustov; Catherine S. Diefenbach; Yasuhiro Oki; Maria Corinna Palanca-Wessels; Mayur Uttarwar; Martha Li; Jing Yang; Eric D. Jacobsen

doi:10.1080/10428194.2016.1256481

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

Nancy L. Bartlett, Mitchell R. Smith, Tanya Siddiqi, Ranjana H. Advani, Owen A. O’Connor, Jeff P. Sharman, Tatyana Feldman, Kerry J. Savage, Andrei R. Shustov, Catherine S. Diefenbach, Yasuhiro Oki, Maria Corinna Palanca-Wessels, Mayur Uttarwar, Martha Li, Jing Yang, Eric D. Jacobsen

Lymphoma-Myeloma

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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).

Original language	English (US)
Pages (from-to)	1607-1616
Number of pages	10
Journal	Leukemia and Lymphoma
Volume	58
Issue number	7
DOIs	https://doi.org/10.1080/10428194.2016.1256481
State	Published - Jul 3 2017

Keywords

DLBCL
antibody-based immunotherapy
antibody-drug conjugate
immunotherapy
lymphoma

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1080/10428194.2016.1256481

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Bartlett, N. L., Smith, M. R., Siddiqi, T., Advani, R. H., O’Connor, O. A., Sharman, J. P., Feldman, T., Savage, K. J., Shustov, A. R., Diefenbach, C. S., Oki, Y., Palanca-Wessels, M. C., Uttarwar, M., Li, M., Yang, J., & Jacobsen, E. D. (2017). Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry. Leukemia and Lymphoma, 58(7), 1607-1616. https://doi.org/10.1080/10428194.2016.1256481

Bartlett, NL, Smith, MR, Siddiqi, T, Advani, RH, O’Connor, OA, Sharman, JP, Feldman, T, Savage, KJ, Shustov, AR, Diefenbach, CS, Oki, Y, Palanca-Wessels, MC, Uttarwar, M, Li, M, Yang, J & Jacobsen, ED 2017, 'Brentuximab vedotin activity in diffuse large B-cell lymphoma with CD30 undetectable by visual assessment of conventional immunohistochemistry', Leukemia and Lymphoma, vol. 58, no. 7, pp. 1607-1616. https://doi.org/10.1080/10428194.2016.1256481

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title = "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, antibody-drug conjugate, immunotherapy, lymphoma",

author = "Bartlett, {Nancy L.} and Smith, {Mitchell R.} and Tanya Siddiqi and Advani, {Ranjana H.} and O{\textquoteright}Connor, {Owen A.} and Sharman, {Jeff P.} and Tatyana Feldman and Savage, {Kerry J.} and Shustov, {Andrei R.} and Diefenbach, {Catherine S.} and Yasuhiro Oki and Palanca-Wessels, {Maria Corinna} and Mayur Uttarwar and Martha Li and Jing Yang and Jacobsen, {Eric D.}",

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doi = "10.1080/10428194.2016.1256481",

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AU - Bartlett, Nancy L.

AU - Smith, Mitchell R.

AU - Siddiqi, Tanya

AU - Advani, Ranjana H.

AU - O’Connor, Owen A.

AU - Sharman, Jeff P.

AU - Feldman, Tatyana

AU - Savage, Kerry J.

AU - Shustov, Andrei R.

AU - Diefenbach, Catherine S.

AU - Oki, Yasuhiro

AU - Palanca-Wessels, Maria Corinna

AU - Uttarwar, Mayur

AU - Li, Martha

AU - Yang, Jing

AU - Jacobsen, Eric D.

PY - 2017/7/3

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N2 - 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).

AB - 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).

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

Abstract

Keywords

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