Ofatumumab As Single-Agent CD20 Immunotherapy in
Fludarabine-Refractory Chronic lymphocytic Leukemia

J 2010

Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic lymphocytic Leukemia

WIERDA, William G.; Thomas J. KIPPS; Jiří MAYER; Stephan STILGENBAUER; Cathy D. WILLIAMS et. al.

Basic information

Original name

Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic lymphocytic Leukemia

Authors

WIERDA, William G. (840 United States of America, guarantor); Thomas J. KIPPS (840 United States of America); Jiří MAYER (203 Czech Republic, belonging to the institution); Stephan STILGENBAUER (276 Germany); Cathy D. WILLIAMS (840 United States of America); Andrzej HELLMANN (616 Poland); Tadeusz ROBAK (616 Poland); Richard R. FURMAN (840 United States of America); Peter HILLMEN (840 United States of America); Marek TRNĚNÝ (203 Czech Republic); Martin J.S. DYER (840 United States of America); Swami PADMANABHAN (208 Denmark); Magdalena PIOTROWSKA (642 Romania); Tomáš KOZÁK (203 Czech Republic); Geoffrey CHAN (840 United States of America); Randy DAVIS (840 United States of America); Nedjad LOSIC (840 United States of America); Joris WILMS (840 United States of America); Charlotte A. RUSSELL (840 United States of America) and Anders ÖSTERBORG (752 Sweden)

Edition

Journal of Clinical Oncology, 2010, 0732-183X

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

Impact factor

Impact factor: 18.970

RIV identification code

RIV/00216224:14110/10:00051390

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1200/JCO.2009.25.3187

UT WoS

000276152200022

Keywords in English

PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PHASE-II MULTICENTER; PLUS CYCLOPHOSPHAMIDE; MONOCLONAL-ANTIBODIES; FOLLICULAR LYMPHOMA; ANTI-CD20 ANTIBODY; RITUXIMAB THERAPY; ALEMTUZUMAB; SURVIVAL; PATIENT

Abstract

V originále

New treatments are needed for patients with fludarabine-and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or patients with fludarabine-refractory CLL with bulky (> 5 cm) lymphadenopathy (BF-ref) who are less suitable for alemtuzumab treatment; these groups have poor outcomes with available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL. Patients and Methods Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 = 300 mg; doses 2 to 12 = 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24. Results This planned interim analysis included 138 treated patients with FA-ref (n = 59) and BF-ref (n = 79) CLL. The overall response rates (primary end point) were 58% and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia. Conclusion Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.

Cite

WIERDA, William G.; Thomas J. KIPPS; Jiří MAYER; Stephan STILGENBAUER; Cathy D. WILLIAMS; Andrzej HELLMANN; Tadeusz ROBAK; Richard R. FURMAN; Peter HILLMEN; Marek TRNĚNÝ; Martin J.S. DYER; Swami PADMANABHAN; Magdalena PIOTROWSKA; Tomáš KOZÁK; Geoffrey CHAN; Randy DAVIS; Nedjad LOSIC; Joris WILMS; Charlotte A. RUSSELL and Anders ÖSTERBORG. Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic lymphocytic Leukemia. Journal of Clinical Oncology. 2010, vol. 28, No 10, p. 1749-1755. ISSN 0732-183X. Available from: https://dx.doi.org/10.1200/JCO.2009.25.3187.

@article{888373,
   author = {Wierda, William G. and Kipps, Thomas J. and Mayer, Jiří and Stilgenbauer, Stephan and Williams, Cathy D. and Hellmann, Andrzej and Robak, Tadeusz and Furman, Richard R. and Hillmen, Peter and Trněný, Marek and Dyer, Martin J.S. and Padmanabhan, Swami and Piotrowska, Magdalena and Kozák, Tomáš and Chan, Geoffrey and Davis, Randy and Losic, Nedjad and Wilms, Joris and Russell, Charlotte A. and Österborg, Anders},
   article_number = {10},
   doi = {http://dx.doi.org/10.1200/JCO.2009.25.3187},
   keywords = {PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PHASE-II MULTICENTER; PLUS CYCLOPHOSPHAMIDE; MONOCLONAL-ANTIBODIES; FOLLICULAR LYMPHOMA; ANTI-CD20 ANTIBODY; RITUXIMAB THERAPY; ALEMTUZUMAB; SURVIVAL; PATIENT},
   language = {eng},
   issn = {0732-183X},
   journal = {Journal of Clinical Oncology},
   title = {Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic lymphocytic Leukemia},
   volume = {28},
   year = {2010}
}

TY  - JOUR
ID  - 888373
AU  - Wierda, William G. - Kipps, Thomas J. - Mayer, Jiří - Stilgenbauer, Stephan - Williams, Cathy D. - Hellmann, Andrzej - Robak, Tadeusz - Furman, Richard R. - Hillmen, Peter - Trněný, Marek - Dyer, Martin J.S. - Padmanabhan, Swami - Piotrowska, Magdalena - Kozák, Tomáš - Chan, Geoffrey - Davis, Randy - Losic, Nedjad - Wilms, Joris - Russell, Charlotte A. - Österborg, Anders
PY  - 2010
TI  - Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic lymphocytic Leukemia
JF  - Journal of Clinical Oncology
VL  - 28
IS  - 10
SP  - 1749-1755
EP  - 1749-1755
SN  - 0732183X
KW  - PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
KW  - PHASE-II MULTICENTER
KW  - PLUS CYCLOPHOSPHAMIDE
KW  - MONOCLONAL-ANTIBODIES
KW  - FOLLICULAR LYMPHOMA
KW  - ANTI-CD20 ANTIBODY
KW  - RITUXIMAB THERAPY
KW  - ALEMTUZUMAB
KW  - SURVIVAL
KW  - PATIENT
N2  - New treatments are needed for patients with fludarabine-and alemtuzumab-refractory (FA-ref) chronic lymphocytic leukemia (CLL) or patients with fludarabine-refractory CLL with bulky (> 5 cm) lymphadenopathy (BF-ref) who are less suitable for alemtuzumab treatment; these groups have poor outcomes with available salvage regimens. Ofatumumab (HuMax-CD20) is a human monoclonal antibody targeting a distinct small-loop epitope on the CD20 molecule. We conducted an international clinical study to evaluate the efficacy and safety of ofatumumab in patients with FA-ref and BF-ref CLL. Patients and Methods Patients received eight weekly infusions of ofatumumab followed by four monthly infusions during a 24-week period (dose 1 = 300 mg; doses 2 to 12 = 2,000 mg); response by an independent review committee (1996 National Cancer Institute Working Group criteria) was assessed every 4 weeks until week 24 and then every 3 months until month 24. Results This planned interim analysis included 138 treated patients with FA-ref (n = 59) and BF-ref (n = 79) CLL. The overall response rates (primary end point) were 58% and 47% in the FA-ref and BF-ref groups, respectively. Complete resolution of constitutional symptoms and improved performance status occurred in 57% and 48% of patients, respectively. Median progression-free survival and overall survival times were 5.7 and 13.7 months in the FA-ref group, respectively, and 5.9 and 15.4 months in the BF-ref group, respectively. The most common adverse events during treatment were infusion reactions and infections, which were primarily grade 1 or 2 events. Hematologic events during treatment included anemia and neutropenia. Conclusion Ofatumumab is an active, well-tolerated treatment providing clear clinical improvements for fludarabine-refractory patients with very poor-prognosis CLL.
ER  -

WIERDA, William G.; Thomas J. KIPPS; Jiří MAYER; Stephan STILGENBAUER; Cathy D. WILLIAMS; Andrzej HELLMANN; Tadeusz ROBAK; Richard R. FURMAN; Peter HILLMEN; Marek TRNĚNÝ; Martin J.S. DYER; Swami PADMANABHAN; Magdalena PIOTROWSKA; Tomáš KOZÁK; Geoffrey CHAN; Randy DAVIS; Nedjad LOSIC; Joris WILMS; Charlotte A. RUSSELL and Anders ÖSTERBORG. Ofatumumab As Single-Agent CD20 Immunotherapy in Fludarabine-Refractory Chronic lymphocytic Leukemia. \textit{Journal of Clinical Oncology}. 2010, vol.~28, No~10, p.~1749-1755. ISSN~0732-183X. Available from: https://dx.doi.org/10.1200/JCO.2009.25.3187.

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