Originally published as JCO Early Release 10.1200/JCO.2005.05.0401 on November 6 2006
Journal of Clinical Oncology, Vol 24, No 34 (December 1), 2006: pp. 5343-5349
© 2006 American Society of Clinical Oncology.
Clinical Efficacy of Lenalidomide in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of a Phase II Study
Asher Chanan-Khan,
Kena C. Miller,
Laurie Musial,
David Lawrence,
Swaminathan Padmanabhan,
Kenichi Takeshita,
Carl W. Porter,
David W. Goodrich,
Zale P. Bernstein,
Paul Wallace,
David Spaner,
Alice Mohr,
Catriona Byrne,
Francisco Hernandez-Ilizaliturri,
Cynthia Chrystal,
Petr Starostik,
Myron S. Czuczman
From the Departments of Medicine, Pharmacology and Therapeutics, Biostatistics, and Pathology, Roswell Park Cancer Institute, Buffalo, NY; Celgene Corporation, Summit, NJ; and Toronto Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada
Address reprint requests to Asher Chanan-Khan, MD, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton St, Buffalo, NY 14263; e-mail: asher.chanan-khan{at}roswellpark.org
PURPOSE: Patients with relapsed or refractory chronic lymphocytic leukemia (CLL) have profound immune defects and limited treatment options. Given the dramatic activity of lenalidomide in other B-cell malignancies and its pleotropic immunomodulatory effects, we conducted a phase II trial of this agent in CLL.
PATIENTS AND METHODS: Patients with relapsed or refractory B-cell CLL (B-CLL) were eligible if they required treatment as per the National Cancer Institute Working Group 1996 guidelines. Lenalidomide was administered orally at 25 mg on days 1 through 21 of a 28-day cycle. Response was assessed after each cycle. Patients were to continue treatment until disease progression, unacceptable toxicity, or complete remission. Rituximab was added to lenalidomide on disease progression.
RESULTS: Forty-five patients were enrolled, with a median age of 64 years. Sixty-four percent of the patients had Rai stage III or IV disease, and 51% were refractory to fludarabine. The overall response rate was 47%, with 9% of the patients attaining a complete remission. Fatigue, thrombocytopenia, and neutropenia were the most common adverse effects noted in 83%, 78%, and 78% of the patients, respectively.
CONCLUSION: Lenalidomide is clinically active in patients with relapsed or refractory B-CLL. These findings are encouraging and warrant further investigation of this agent in the treatment of this disorder.
published online ahead of print at www.jco.org on November 6, 2006.
Supported by Celgene Corporation, Summit, NJ.
Presented in part at the XI International Workshop on Chronic Lymphocytic Leukemia, September 1618, 2005, Brooklyn, NY; the 47th Annual Meeting of the American Society of Hematology, December 1013, 2005, Atlanta, GA; and the 41st Annual Meeting of the American Society of Clinical Oncology, May 1317, 2005, Orlando, FL.
Authors disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike Complore Connotea Del.icio.us Digg Facebook Reddit Technorati Twitter What's this?
Related Correspondence
- Tumor Lysis Syndrome/Tumor Flare Reaction in Lenalidomide-Treated Chronic Lymphocytic Leukemia
Laure A. Moutouh-de Parseval, Lilia Weiss, Robert J. DeLap, Robert D. Knight, and Jerome B. Zeldis
JCO 2007 25: 5047
[Full Text]
This article has been cited by other articles:

|
 |

|
 |
 
T. E. Witzig, P. H. Wiernik, T. Moore, C. Reeder, C. Cole, G. Justice, H. Kaplan, M. Voralia, D. Pietronigro, K. Takeshita, et al.
Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
November 10, 2009;
27(32):
5404 - 5409.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. G. Ramsay and J. G. Gribben
Immune dysfunction in chronic lymphocytic leukemia T cells and lenalidomide as an immunomodulatory drug
Haematologica,
September 1, 2009;
94(9):
1198 - 1202.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Aue, N. Njuguna, X. Tian, S. Soto, T. Hughes, B. Vire, K. Keyvanfar, F. Gibellini, J. Valdez, C. Boss, et al.
Lenalidomide-induced upregulation of CD80 on tumor cells correlates with T-cell activation, the rapid onset of a cytokine release syndrome and leukemic cell clearance in chronic lymphocytic leukemia
Haematologica,
September 1, 2009;
94(9):
1266 - 1273.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Stilgenbauer, T. Zenz, D. Winkler, A. Buhler, R. F. Schlenk, S. Groner, R. Busch, M. Hensel, U. Duhrsen, J. Finke, et al.
Subcutaneous Alemtuzumab in Fludarabine-Refractory Chronic Lymphocytic Leukemia: Clinical Results and Prognostic Marker Analyses From the CLL2H Study of the German Chronic Lymphocytic Leukemia Study Group
J. Clin. Oncol.,
August 20, 2009;
27(24):
3994 - 4001.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Delgado, S. Pillai, N. Phillips, S. Brunet, G. Pratt, J. Briones, R. Lovell, R. Martino, J. Ewing, A. Sureda, et al.
Does reduced-intensity allogeneic transplantation confer a survival advantage to patients with poor prognosis chronic lymphocytic leukaemia? A case-control retrospective analysis
Ann. Onc.,
July 12, 2009;
(2009)
mdp259v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Xu, J. Li, G. D. Ferguson, F. Mercurio, G. Khambatta, L. Morrison, A. Lopez-Girona, L. G. Corral, D. R. Webb, B. L. Bennett, et al.
Immunomodulatory drugs reorganize cytoskeleton by modulating Rho GTPases
Blood,
July 9, 2009;
114(2):
338 - 345.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Gorgun, A. G. Ramsay, T. A. W. Holderried, D. Zahrieh, R. Le Dieu, F. Liu, J. Quackenbush, C. M. Croce, and J. G. Gribben
E{micro}-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction
PNAS,
April 14, 2009;
106(15):
6250 - 6255.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. D. Cheson and M. J. Rummel
Bendamustine: Rebirth of an Old Drug
J. Clin. Oncol.,
March 20, 2009;
27(9):
1492 - 1501.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Ruan, K. Hajjar, S. Rafii, and J. P. Leonard
Angiogenesis and antiangiogenic therapy in non-Hodgkin's lymphoma
Ann. Onc.,
March 1, 2009;
20(3):
413 - 424.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. E. Kay
The yin and yang of lenalidomide
Blood,
December 15, 2008;
112(13):
4785 - 4786.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Lapalombella, B. Yu, G. Triantafillou, Q. Liu, J. P. Butchar, G. Lozanski, A. Ramanunni, L. L. Smith, W. Blum, L. Andritsos, et al.
Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells
Blood,
December 15, 2008;
112(13):
5180 - 5189.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Sorror, B. E. Storer, B. M. Sandmaier, M. Maris, J. Shizuru, R. Maziarz, E. Agura, T. R. Chauncey, M. A. Pulsipher, P. A. McSweeney, et al.
Five-Year Follow-Up of Patients With Advanced Chronic Lymphocytic Leukemia Treated With Allogeneic Hematopoietic Cell Transplantation After Nonmyeloablative Conditioning
J. Clin. Oncol.,
October 20, 2008;
26(30):
4912 - 4920.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Chanan-Khan, A. Whitworth, N. Bangia, C. W. Porter, and K. Lee
Lenalidomide-Associated Tumor Flare Reaction Is Manageable in Patients With Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
October 10, 2008;
26(29):
4851 - 4852.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Andritsos, T. S. Lin, W. Blum, C. Kefauver, A. J. Johnson, and J. C. Byrd
In Reply:
J. Clin. Oncol.,
October 10, 2008;
26(29):
4852 - 4853.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. S. Lin
Lenalidomide: what is the right dose in CLL?
Blood,
June 1, 2008;
111(11):
5268 - 5268.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Ferrajoli, B.-N. Lee, E. J. Schlette, S. M. O'Brien, H. Gao, S. Wen, W. G. Wierda, Z. Estrov, S. Faderl, E. N. Cohen, et al.
Lenalidomide induces complete and partial remissions in patients with relapsed and refractory chronic lymphocytic leukemia
Blood,
June 1, 2008;
111(11):
5291 - 5297.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Andritsos, A. J. Johnson, G. Lozanski, W. Blum, C. Kefauver, F. Awan, L. L. Smith, R. Lapalombella, S. E. May, C. A. Raymond, et al.
Higher Doses of Lenalidomide Are Associated With Unacceptable Toxicity Including Life-Threatening Tumor Flare in Patients With Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
May 20, 2008;
26(15):
2519 - 2525.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Chanan-Khan and B. D. Cheson
Lenalidomide for the Treatment of B-Cell Malignancies
J. Clin. Oncol.,
March 20, 2008;
26(9):
1544 - 1552.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. G. Wierda
Treatments for Patients with Chronic Lymphocytic Leukemia
ASCO Educational Book,
January 1, 2008;
2008(1):
297 - 305.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. A. Blum, D. Young, S. Broering, M. S. Lucas, B. Fischer, T. S. Lin, M. R. Grever, and J. C. Byrd
Computed Tomography Scans Do Not Improve the Predictive Power of 1996 National Cancer Institute Sponsored Working Group Chronic Lymphocytic Leukemia Response Criteria
J. Clin. Oncol.,
December 10, 2007;
25(35):
5624 - 5629.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. A. Fine, L. Kim, P. S. Albert, J. P. Duic, H. Ma, W. Zhang, T. Tohnya, W. D. Figg, and C. Royce
A Phase I Trial of Lenalidomide in Patients with Recurrent Primary Central Nervous System Tumors
Clin. Cancer Res.,
December 1, 2007;
13(23):
7101 - 7106.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Chen, H. Lau, L. Kong, G. Kumar, J. B. Zeldis, R. Knight, and O. L. Laskin
Pharmacokinetics of Lenalidomide in Subjects With Various Degrees of Renal Impairment and in Subjects on Hemodialysis
J. Clin. Pharmacol.,
December 1, 2007;
47(12):
1466 - 1475.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. A. Moutouh-de Parseval, L. Weiss, R. J. DeLap, R. D. Knight, and J. B. Zeldis
Tumor Lysis Syndrome/Tumor Flare Reaction in Lenalidomide-Treated Chronic Lymphocytic Leukemia
J. Clin. Oncol.,
November 1, 2007;
25(31):
5047 - 5047.
[Full Text]
[PDF]
|
 |
|
|