Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma

Kamal Sharma, John E. Janik, Deirdre O'Mahony, Donn Stewart, Stefania Pittaluga, Maryalice Stetler-Stevenson, Elaine S. Jaffe, Mark Raffeld, Thomas A. Fleisher, Cathryn C. Lee, Seth M. Steinberg, Thomas A. Waldmann, John C. Morris

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Abstract

Purpose: Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression-free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated ATL. Experimental Design: Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a singleinstitution, nonrandomized, open-label phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks. Results: Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 of 29 patients [95% confidence interval (CI), 32.5%-70.6%]. The 15 patients who responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression-free survival was 2.0 months. Median overall survival was 5.9 months. The most common adverse events were 2 with vasovagal episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%) grade 3 and (17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia (24%), and thrombocytopenia (10%). All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14%) of patients. Conclusions: Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multidrug therapies for ATL.

Original languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2017

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Adult T Cell Leukemia Lymphoma
Human T-lymphotropic virus 1
T-Lymphocytes
Disease-Free Survival
alemtuzumab
Lymphopenia
Survival
Leukopenia
Therapeutics
Neutropenia
Cytomegalovirus
Thrombocytopenia
Antiviral Agents
Anemia
Research Design
Confidence Intervals

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sharma, K., Janik, J. E., O'Mahony, D., Stewart, D., Pittaluga, S., Stetler-Stevenson, M., ... Morris, J. C. (2017). Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Clinical Cancer Research, 23(1), 35-42. https://doi.org/10.1158/1078-0432.CCR-16-1022

Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. / Sharma, Kamal; Janik, John E.; O'Mahony, Deirdre; Stewart, Donn; Pittaluga, Stefania; Stetler-Stevenson, Maryalice; Jaffe, Elaine S.; Raffeld, Mark; Fleisher, Thomas A.; Lee, Cathryn C.; Steinberg, Seth M.; Waldmann, Thomas A.; Morris, John C.

In: Clinical Cancer Research, Vol. 23, No. 1, 01.01.2017, p. 35-42.

Research output: Contribution to journalArticle

Sharma, K, Janik, JE, O'Mahony, D, Stewart, D, Pittaluga, S, Stetler-Stevenson, M, Jaffe, ES, Raffeld, M, Fleisher, TA, Lee, CC, Steinberg, SM, Waldmann, TA & Morris, JC 2017, 'Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma', Clinical Cancer Research, vol. 23, no. 1, pp. 35-42. https://doi.org/10.1158/1078-0432.CCR-16-1022
Sharma, Kamal ; Janik, John E. ; O'Mahony, Deirdre ; Stewart, Donn ; Pittaluga, Stefania ; Stetler-Stevenson, Maryalice ; Jaffe, Elaine S. ; Raffeld, Mark ; Fleisher, Thomas A. ; Lee, Cathryn C. ; Steinberg, Seth M. ; Waldmann, Thomas A. ; Morris, John C. / Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 1. pp. 35-42.
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abstract = "Purpose: Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression-free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated ATL. Experimental Design: Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a singleinstitution, nonrandomized, open-label phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks. Results: Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 of 29 patients [95{\%} confidence interval (CI), 32.5{\%}-70.6{\%}]. The 15 patients who responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression-free survival was 2.0 months. Median overall survival was 5.9 months. The most common adverse events were 2 with vasovagal episodes (7{\%}) and 3 with hypotensive episodes (10{\%}), leukopenia (41{\%}) grade 3 and (17{\%}) grade 4, lymphocytopenia (59{\%}) grade 3, neutropenia (31{\%}) grade 3, anemia (24{\%}), and thrombocytopenia (10{\%}). All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14{\%}) of patients. Conclusions: Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multidrug therapies for ATL.",
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AU - Stewart, Donn

AU - Pittaluga, Stefania

AU - Stetler-Stevenson, Maryalice

AU - Jaffe, Elaine S.

AU - Raffeld, Mark

AU - Fleisher, Thomas A.

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