Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma

Jonathan L. Berkowitz; John E. Janik; Donn M. Stewart; Elaine S. Jaffe; Maryalice Stetler-Stevenson; Joanna H. Shih; Thomas A. Fleisher; Maria Turner; Nicole E. Urquhart; Gilian H. Wharfe; William D. Figg; Cody J. Peer; Carolyn K. Goldman; Thomas A. Waldmann; John C. Morris

doi:10.1016/j.clim.2014.09.012

Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma

Jonathan L. Berkowitz, John E. Janik, Donn M. Stewart, Elaine S. Jaffe, Maryalice Stetler-Stevenson, Joanna H. Shih, Thomas A. Fleisher, Maria Turner, Nicole E. Urquhart, Gilian H. Wharfe, William D. Figg, Cody J. Peer, Carolyn K. Goldman, Thomas A. Waldmann^*, John C. Morris

^*Corresponding author for this work

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

55 Scopus citations

Abstract

Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8. mg/kg. Up to 8. mg/kg of daclizumab administered every 3. weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.

Original language	English
Pages (from-to)	176-187
Number of pages	12
Journal	Clinical Immunology
Volume	155
Issue number	2
DOIs	https://doi.org/10.1016/j.clim.2014.09.012
State	Published - 1 Dec 2014
Externally published	Yes

Keywords

Adult T-cell leukemia/lymphoma
Daclizumab
Human T-cell leukemia virus 1 (HTLV-1) associated ATL
Interleukin-2 receptor alpha
Monoclonal antibody

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10.1016/j.clim.2014.09.012

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Berkowitz, J. L., Janik, J. E., Stewart, D. M., Jaffe, E. S., Stetler-Stevenson, M., Shih, J. H., Fleisher, T. A., Turner, M., Urquhart, N. E., Wharfe, G. H., Figg, W. D., Peer, C. J., Goldman, C. K., Waldmann, T. A., & Morris, J. C. (2014). Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma. Clinical Immunology, 155(2), 176-187. https://doi.org/10.1016/j.clim.2014.09.012

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title = "Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma",

abstract = "Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8. mg/kg. Up to 8. mg/kg of daclizumab administered every 3. weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.",

keywords = "Adult T-cell leukemia/lymphoma, Daclizumab, Human T-cell leukemia virus 1 (HTLV-1) associated ATL, Interleukin-2 receptor alpha, Monoclonal antibody",

author = "Berkowitz, {Jonathan L.} and Janik, {John E.} and Stewart, {Donn M.} and Jaffe, {Elaine S.} and Maryalice Stetler-Stevenson and Shih, {Joanna H.} and Fleisher, {Thomas A.} and Maria Turner and Urquhart, {Nicole E.} and Wharfe, {Gilian H.} and Figg, {William D.} and Peer, {Cody J.} and Goldman, {Carolyn K.} and Waldmann, {Thomas A.} and Morris, {John C.}",

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year = "2014",

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doi = "10.1016/j.clim.2014.09.012",

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Berkowitz, JL, Janik, JE, Stewart, DM, Jaffe, ES, Stetler-Stevenson, M, Shih, JH, Fleisher, TA, Turner, M, Urquhart, NE, Wharfe, GH, Figg, WD, Peer, CJ, Goldman, CK, Waldmann, TA & Morris, JC 2014, 'Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma', Clinical Immunology, vol. 155, no. 2, pp. 176-187. https://doi.org/10.1016/j.clim.2014.09.012

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AU - Berkowitz, Jonathan L.

AU - Janik, John E.

AU - Stewart, Donn M.

AU - Jaffe, Elaine S.

AU - Stetler-Stevenson, Maryalice

AU - Shih, Joanna H.

AU - Fleisher, Thomas A.

AU - Turner, Maria

AU - Urquhart, Nicole E.

AU - Wharfe, Gilian H.

AU - Figg, William D.

AU - Peer, Cody J.

AU - Goldman, Carolyn K.

AU - Waldmann, Thomas A.

AU - Morris, John C.

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N2 - Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8. mg/kg. Up to 8. mg/kg of daclizumab administered every 3. weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.

AB - Interleukin-2 receptor α chain (CD25) is overexpressed in human T-cell leukemia virus 1 associated adult T-cell leukemia/lymphoma (ATL). Daclizumab a humanized monoclonal antibody blocks IL-2 binding by recognizing the interleukin-2 receptor α chain (CD25). We conducted a phase I/II trial of daclizumab in 34 patients with ATL. Saturation of surface CD25 on circulating ATL cells was achieved at all doses; however saturation on ATL cells in lymph nodes required 8. mg/kg. Up to 8. mg/kg of daclizumab administered every 3. weeks was well tolerated. No responses were observed in 18 patients with acute or lymphoma ATL; however, 6 partial responses were observed in 16 chronic and smoldering ATL patients. The pharmacokinetics/pharmacodynamics of daclizumab suggest that high-dose daclizumab would be more effective than low-dose daclizumab in treatment of lymphoid malignancies and autoimmune diseases (e.g., multiple sclerosis) since high-dose daclizumab is required to saturate IL-2R alpha in extravascular sites.

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KW - Human T-cell leukemia virus 1 (HTLV-1) associated ATL

KW - Interleukin-2 receptor alpha

KW - Monoclonal antibody

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SN - 1521-6616

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JO - Clinical Immunology

JF - Clinical Immunology

IS - 2

ER -

Safety, efficacy, and pharmacokinetics/pharmacodynamics of daclizumab (anti-CD25) in patients with adult T-cell leukemia/lymphoma

Abstract

Keywords

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