Chlorambucil plus ofatumumab versus chlorambucil alone in
previously untreated patients with chronic lymphocytic
leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label
phase 3 trial

J 2015

Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial

HILLMEN, P.; T. ROBAK; A. JANSSENS; K.G. BABU; J. KLOCZKO et al.

Základní údaje

Originální název

Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial

Autoři

Vydání

Lancet, New York, Elsevier Science Inc. 2015, 0140-6736

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 44.002

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/15:00084660

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

ILLNESS RATING-SCALE; ELDERLY-PATIENTS; MONOCLONAL-ANTIBODIES; 1ST-LINE TREATMENT; HUMAN CD20;

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 12. 11. 2015 16:44, Soňa Böhmová

Anotace

V originále

Background Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options. Methods We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1: 1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189. Findings We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22.4 months (95% CI 19.0-25.2) in the group assigned to chlorambucil plus ofatumumab compared with 13.1 months (10.6-13.8) in the group assigned to chlorambucil only (hazard ratio 0.57, 95% CI 0.45-0.72; p<0.0001). Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group (109 [50%] patients; vs 98 [43%] given chlorambucil alone), with neutropenia being the most common event (56 [26%] vs 32 [14%]). Grade 3 or greater infections had similar frequency in both groups. Grade 3 or greater infusion-related adverse events were reported in 22 (10%) patients given chlorambucil plus ofatumumab. Five (2%) patients died during treatment in each group. Interpretation Addition of ofatumumab to chlorambucil led to clinically important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities. Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who cannot tolerate more intensive therapy.

Citovat

HILLMEN, P.; T. ROBAK; A. JANSSENS; K.G. BABU; J. KLOCZKO; S. GROSICKI; Michael DOUBEK; P. PANAGIOTIDIS; E. KIMBY; A. SCHUH; A.R. PETTITT; T. BOYD; M. MONTILLO; I.V. GUPTA; O. WRIGHT; I. DIXON; J.L. CAREY; C.N. CHANG; S. LISBY; A. MCKEOWN a F. OFFNER. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. Lancet. New York: Elsevier Science Inc., 2015, roč. 385, č. 9980, s. 1873-1883. ISSN 0140-6736. Dostupné z: https://doi.org/10.1016/S0140-6736(15)60027-7.

@article{1316981,
   author = {Hillmen, P. and Robak, T. and Janssens, A. and Babu, K.G. and Kloczko, J. and Grosicki, S. and Doubek, Michael and Panagiotidis, P. and Kimby, E. and Schuh, A. and Pettitt, A.R. and Boyd, T. and Montillo, M. and Gupta, I.V. and Wright, O. and Dixon, I. and Carey, J.L. and Chang, C.N. and Lisby, S. and McKeown, A. and Offner, F.},
   article_location = {New York},
   article_number = {9980},
   doi = {https://doi.org/10.1016/S0140-6736(15)60027-7},
   keywords = {ILLNESS RATING-SCALE; ELDERLY-PATIENTS; MONOCLONAL-ANTIBODIES; 1ST-LINE TREATMENT; HUMAN CD20;},
   language = {eng},
   issn = {0140-6736},
   journal = {Lancet},
   title = {Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial},
   volume = {385},
   year = {2015}
}

TY  - JOUR
ID  - 1316981
AU  - Hillmen, P. - Robak, T. - Janssens, A. - Babu, K.G. - Kloczko, J. - Grosicki, S. - Doubek, Michael - Panagiotidis, P. - Kimby, E. - Schuh, A. - Pettitt, A.R. - Boyd, T. - Montillo, M. - Gupta, I.V. - Wright, O. - Dixon, I. - Carey, J.L. - Chang, C.N. - Lisby, S. - McKeown, A. - Offner, F.
PY  - 2015
TI  - Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial
JF  - Lancet
VL  - 385
IS  - 9980
SP  - 1873-1883
EP  - 1873-1883
PB  - Elsevier Science Inc.
SN  - 01406736
KW  - ILLNESS RATING-SCALE
KW  - ELDERLY-PATIENTS
KW  - MONOCLONAL-ANTIBODIES
KW  - 1ST-LINE TREATMENT
KW  - HUMAN CD20;
N2  - Background Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options. Methods We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1: 1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189. Findings We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22.4 months (95% CI 19.0-25.2) in the group assigned to chlorambucil plus ofatumumab compared with 13.1 months (10.6-13.8) in the group assigned to chlorambucil only (hazard ratio 0.57, 95% CI 0.45-0.72; p<0.0001). Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group (109 [50%] patients; vs 98 [43%] given chlorambucil alone), with neutropenia being the most common event (56 [26%] vs 32 [14%]). Grade 3 or greater infections had similar frequency in both groups. Grade 3 or greater infusion-related adverse events were reported in 22 (10%) patients given chlorambucil plus ofatumumab. Five (2%) patients died during treatment in each group. Interpretation Addition of ofatumumab to chlorambucil led to clinically important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities. Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who cannot tolerate more intensive therapy.
ER  -

HILLMEN, P.; T. ROBAK; A. JANSSENS; K.G. BABU; J. KLOCZKO; S. GROSICKI; Michael DOUBEK; P. PANAGIOTIDIS; E. KIMBY; A. SCHUH; A.R. PETTITT; T. BOYD; M. MONTILLO; I.V. GUPTA; O. WRIGHT; I. DIXON; J.L. CAREY; C.N. CHANG; S. LISBY; A. MCKEOWN a F. OFFNER. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial. \textit{Lancet}. New York: Elsevier Science Inc., 2015, roč.~385, č.~9980, s.~1873-1883. ISSN~0140-6736. Dostupné z: https://doi.org/10.1016/S0140-6736(15)60027-7.

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