Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 1/2007

01-06-2007 | Original Article

Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas: a phase II study

Authors: Jong Gwang Kim, Sang Kyun Sohn, Yee Soo Chae, Yoon Young Cho, Deok Hwan Yang, Je-Jung Lee, Hyeoung-Joon Kim, Ho Jin Shin, Joo Seop Chung, Goon Jae Cho, Won-Sik Lee, Young-Don Joo, Chang-Hak Sohn, Suk Joong Oh

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2007

Login to get access

Abstract

Purpose

The present study was conducted to evaluate the safety and efficacy of alemtuzumab plus CHOP chemotherapy for patients with peripheral T-cell lymphomas (PTCLs).

Patients and methods

Twenty patients with newly diagnosed PTCLs were enrolled. The treatment consisted of classical CHOP plus alemtuzumab (10 mg i.v. on day 1 and 20 mg i.v. on day 2 in the first cycle, then 30 mg i.v. on day 1 in the subsequent cycles) based on 3-week intervals.

Results

Thirteen complete responses (65.0%) and three partial responses (15.0%) were confirmed, giving an overall response rate of 80.0%. The estimated event-free survival at 1 year was 43.3%. The most severe hematologic adverse event was neutropenia, which occurred with a grade-4 intensity in 18 patients (90.0%). Also, febrile neutropenia was observed in 11 patients (55.0%). Five patients (25%) experienced cytomegalovirus (CMV) reactivation, while three patients developed CMV diseases, such as pneumonitis or retinitis. There were two treatment-related deaths. Based on the high incidence of the adverse infectious and hematologic events, the current study was closed after 20 of the planned 43 patients had been enrolled.

Conclusion

The alemtuzumab plus CHOP chemotherapy seemed to produce active antitumor activity in terms of the complete response rates in patients with PTCLs. However, since high infectious and hematologic toxicities were observed, careful monitoring and early treatment are needed to prevent treatment-related mortality.
Literature
1.
go back to reference Gordon LI, Harrington D, Anderson J, Colgan J, Glick J, Neiman R, Mann R, Resnick GD, M Barcos, Gottlieb A (1992) Comparison of a second generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin’s lymphoma. N Engl J Med 327:1342–1349PubMedCrossRef Gordon LI, Harrington D, Anderson J, Colgan J, Glick J, Neiman R, Mann R, Resnick GD, M Barcos, Gottlieb A (1992) Comparison of a second generation combination chemotherapeutic regimen (m-BACOD) with a standard regimen (CHOP) for advanced diffuse non-Hodgkin’s lymphoma. N Engl J Med 327:1342–1349PubMedCrossRef
2.
go back to reference Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP (1993) Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 328:1002–1006PubMedCrossRef Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP (1993) Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 328:1002–1006PubMedCrossRef
3.
go back to reference Lee CH, Im YH, Ryoo BY, Nam SM, Kim MS, Lee YS, Oh KK, Shim YS, Yoo SY, Lee JO, Kang YK (1998) Primary CHOP chemotherapy followed by involved field radiation therapy in clinical stage I or II aggressive non-Hodgkin’s lymphomas. Cancer Res Treat 30:809–817 Lee CH, Im YH, Ryoo BY, Nam SM, Kim MS, Lee YS, Oh KK, Shim YS, Yoo SY, Lee JO, Kang YK (1998) Primary CHOP chemotherapy followed by involved field radiation therapy in clinical stage I or II aggressive non-Hodgkin’s lymphomas. Cancer Res Treat 30:809–817
4.
go back to reference Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML, Delsol G, De Wolf-Peters C, Falini B, Gatter KC, Grogan TM, Isaacson PG, Knowles DM, Mason DY, Muller-Hermelink H, Pileri SA, Piris MA, Ralfkiaer E, Warnke RA (1994) A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392PubMed Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML, Delsol G, De Wolf-Peters C, Falini B, Gatter KC, Grogan TM, Isaacson PG, Knowles DM, Mason DY, Muller-Hermelink H, Pileri SA, Piris MA, Ralfkiaer E, Warnke RA (1994) A revised European–American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392PubMed
5.
go back to reference Melnyk A, Rodrguez A, Pugh WC, Cabannillas F. Evaluation of the revised European–American lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin’s lymphoma. Blood 89:4514–4520 Melnyk A, Rodrguez A, Pugh WC, Cabannillas F. Evaluation of the revised European–American lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin’s lymphoma. Blood 89:4514–4520
6.
go back to reference McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825–2833PubMed McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16:2825–2833PubMed
7.
go back to reference Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B (2005) Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23:4117–4126PubMedCrossRef Feugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferme C, Christian B, Lepage E, Tilly H, Morschauser F, Gaulard P, Salles G, Bosly A, Gisselbrecht C, Reyes F, Coiffier B (2005) Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 23:4117–4126PubMedCrossRef
8.
go back to reference Salisbury JR, Rapson NT, Codd JD, Rogers MV, Nethersell AB (1994) Immunohistochemical analysis of CDw52 antigen expression in non-Hodgkin’s lymphomas. J Clin Pathol 47:313–317PubMed Salisbury JR, Rapson NT, Codd JD, Rogers MV, Nethersell AB (1994) Immunohistochemical analysis of CDw52 antigen expression in non-Hodgkin’s lymphomas. J Clin Pathol 47:313–317PubMed
9.
go back to reference Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, Catovsky V (1998) Levels of expression of CD 52 in normal and leukemic B and T cells: correlations with in vivo therapeutic responses to Campath-1H. Leuk Res 22:185–191PubMedCrossRef Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Dyer MJ, Catovsky V (1998) Levels of expression of CD 52 in normal and leukemic B and T cells: correlations with in vivo therapeutic responses to Campath-1H. Leuk Res 22:185–191PubMedCrossRef
10.
go back to reference Lundin J, Kimby E, Bjorkholm M, Broliden PA, Celsing F, Hjalmar V, Mollgard L, Rebello P, Hale G, Waldmann H, Mellstedt H, Osterborg A (2002) Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath) as first line treatment for patients with B-cell chronic lymphocytic leukemia. Blood 100:768–773PubMedCrossRef Lundin J, Kimby E, Bjorkholm M, Broliden PA, Celsing F, Hjalmar V, Mollgard L, Rebello P, Hale G, Waldmann H, Mellstedt H, Osterborg A (2002) Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath) as first line treatment for patients with B-cell chronic lymphocytic leukemia. Blood 100:768–773PubMedCrossRef
11.
go back to reference Dearden CE, Matutes E, Cazin B, Tjonnfjord GE, Parreira A, Nomdedeu B, Leoni P, Clark FJ, Radia D, Rassam SM, Roques T, Ketterer N, Brito-Babapulle V, Dyer MJ, Catovsky D (2001) High remission rate in T-cell prolymphocytic leukemia with Campath-1H. Blood 98:1721–1726PubMedCrossRef Dearden CE, Matutes E, Cazin B, Tjonnfjord GE, Parreira A, Nomdedeu B, Leoni P, Clark FJ, Radia D, Rassam SM, Roques T, Ketterer N, Brito-Babapulle V, Dyer MJ, Catovsky D (2001) High remission rate in T-cell prolymphocytic leukemia with Campath-1H. Blood 98:1721–1726PubMedCrossRef
12.
go back to reference Lundin J, Hagberg H, Repp R, Cavallin-Stahl E, Freden S, Juliusson G, Rosenblad E, Tjonnfjord G, Wiklund T, Osterborg A (2003) Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 101:4267–4272PubMedCrossRef Lundin J, Hagberg H, Repp R, Cavallin-Stahl E, Freden S, Juliusson G, Rosenblad E, Tjonnfjord G, Wiklund T, Osterborg A (2003) Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome. Blood 101:4267–4272PubMedCrossRef
13.
go back to reference Enblad G, Hagberg H, Erlanson M, Lunding J, MacDonald AP, Repp R, Schetelig J, Seipelt G, Osterborg A (2004) A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood 103:2920–2924PubMedCrossRef Enblad G, Hagberg H, Erlanson M, Lunding J, MacDonald AP, Repp R, Schetelig J, Seipelt G, Osterborg A (2004) A pilot study of alemtuzumab (anti-CD52 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood 103:2920–2924PubMedCrossRef
14.
go back to reference Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphoma. J Clin Oncol 17:1244–1253PubMed Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP (1999) Report of an international workshop to standardize response criteria for non-Hodgkin’s lymphoma. J Clin Oncol 17:1244–1253PubMed
15.
go back to reference Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10PubMedCrossRef Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10PubMedCrossRef
16.
go back to reference Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C, Cazals-Hatem D, Bosly A, Xerri L, Tilly H, Berger F, Bouhabdallah R, Diebold J (1998) Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Blood 92:76–82PubMed Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C, Cazals-Hatem D, Bosly A, Xerri L, Tilly H, Berger F, Bouhabdallah R, Diebold J (1998) Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Blood 92:76–82PubMed
17.
go back to reference Kim K, Kim WS, Jung CW, Im YH, Kang WK, Lee MH, Park CH, Ko YH, Ree HJ, Park K (2002) Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the revised European–American lymphoma (REAL) classification. Eur J Cancer 38:75–81PubMedCrossRef Kim K, Kim WS, Jung CW, Im YH, Kang WK, Lee MH, Park CH, Ko YH, Ree HJ, Park K (2002) Clinical features of peripheral T-cell lymphomas in 78 patients diagnosed according to the revised European–American lymphoma (REAL) classification. Eur J Cancer 38:75–81PubMedCrossRef
18.
go back to reference Kim JG, Sohn SK, Chae YS, Kim DH, Baek JH, Lee KB, Lee JJ, Chung IJ, Kim HJ, Yang DH, Lee WS, Joo YD, Sohn CH (2006) CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas. Cancer Chemother Pharmacol 58:35–39PubMedCrossRef Kim JG, Sohn SK, Chae YS, Kim DH, Baek JH, Lee KB, Lee JJ, Chung IJ, Kim HJ, Yang DH, Lee WS, Joo YD, Sohn CH (2006) CHOP plus etoposide and gemcitabine (CHOP-EG) as front-line chemotherapy for patients with peripheral T cell lymphomas. Cancer Chemother Pharmacol 58:35–39PubMedCrossRef
19.
go back to reference Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR (2002) Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561PubMedCrossRef Keating MJ, Flinn I, Jain V, Binet JL, Hillmen P, Byrd J, Albitar M, Brettman L, Santabarbara P, Wacker B, Rai KR (2002) Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554–3561PubMedCrossRef
20.
go back to reference Lundin J, Porwit-MacDonald A, Rossmann ED, Karlsson C, Edman P, Rezvany MR, Kimby E, Osterborg A, Mellstedt H (2004) Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, Campath-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukemia. Leukemia 18:484–490PubMedCrossRef Lundin J, Porwit-MacDonald A, Rossmann ED, Karlsson C, Edman P, Rezvany MR, Kimby E, Osterborg A, Mellstedt H (2004) Cellular immune reconstitution after subcutaneous alemtuzumab (anti-CD52 monoclonal antibody, Campath-1H) treatment as first-line therapy for B-cell chronic lymphocytic leukemia. Leukemia 18:484–490PubMedCrossRef
Metadata
Title
Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas: a phase II study
Authors
Jong Gwang Kim
Sang Kyun Sohn
Yee Soo Chae
Yoon Young Cho
Deok Hwan Yang
Je-Jung Lee
Hyeoung-Joon Kim
Ho Jin Shin
Joo Seop Chung
Goon Jae Cho
Won-Sik Lee
Young-Don Joo
Chang-Hak Sohn
Suk Joong Oh
Publication date
01-06-2007
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 1/2007
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-007-0469-9

Other articles of this Issue 1/2007

Cancer Chemotherapy and Pharmacology 1/2007 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine