Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Fischer, K, Al-Sawaf, O, Bahlo, J, Fink, A-M, Tandon, M, Dixon, M, Robrecht, S, Warburton, S, Humphrey, K, Samoylova, O, Liberati, AM, Pinilla-Ibarz, J, Opat, S, Sivcheva, L, Le Dû, K, Fogliatto, LM, Niemann, CU, Weinkove, R, Robinson, S, Kipps, TJ, Boettcher, S, Tausch, E, Humerickhouse, R, Eichhorst, B, Wendtner, C-M, Langerak, AW, Kreuzer, K-A, Ritgen, M, Goede, V, Stilgenbauer, S, Mobasher, M & Hallek, M 2019, 'Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions' The New England journal of medicine, vol. 380, no. 23, pp. 2225-2236. https://doi.org/10.1056/NEJMoa1815281

APA

Fischer, K., Al-Sawaf, O., Bahlo, J., Fink, A-M., Tandon, M., Dixon, M., ... Hallek, M. (2019). Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. The New England journal of medicine, 380(23), 2225-2236. https://doi.org/10.1056/NEJMoa1815281

CBE

Fischer K, Al-Sawaf O, Bahlo J, Fink A-M, Tandon M, Dixon M, Robrecht S, Warburton S, Humphrey K, Samoylova O, Liberati AM, Pinilla-Ibarz J, Opat S, Sivcheva L, Le Dû K, Fogliatto LM, Niemann CU, Weinkove R, Robinson S, Kipps TJ, Boettcher S, Tausch E, Humerickhouse R, Eichhorst B, Wendtner C-M, Langerak AW, Kreuzer K-A, Ritgen M, Goede V, Stilgenbauer S, Mobasher M, Hallek M. 2019. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. The New England journal of medicine. 380(23):2225-2236. https://doi.org/10.1056/NEJMoa1815281

MLA

Vancouver

Fischer K, Al-Sawaf O, Bahlo J, Fink A-M, Tandon M, Dixon M et al. Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. The New England journal of medicine. 2019 Jun 6;380(23):2225-2236. https://doi.org/10.1056/NEJMoa1815281

Author

Fischer, Kirsten ; Al-Sawaf, Othman ; Bahlo, Jasmin ; Fink, Anna-Maria ; Tandon, Maneesh ; Dixon, Mark ; Robrecht, Sandra ; Warburton, Simon ; Humphrey, Kathryn ; Samoylova, Olga ; Liberati, Anna M ; Pinilla-Ibarz, Javier ; Opat, Stephen ; Sivcheva, Liliya ; Le Dû, Katell ; Fogliatto, Laura M ; Niemann, Carsten U ; Weinkove, Robert ; Robinson, Sue ; Kipps, Thomas J ; Boettcher, Sebastian ; Tausch, Eugen ; Humerickhouse, Rod ; Eichhorst, Barbara ; Wendtner, Clemens-Martin ; Langerak, Anton W ; Kreuzer, Karl-Anton ; Ritgen, Matthias ; Goede, Valentin ; Stilgenbauer, Stephan ; Mobasher, Mehrdad ; Hallek, Michael. / Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. In: The New England journal of medicine. 2019 ; Vol. 380, No. 23. pp. 2225-2236.

Bibtex

@article{7063cf0e350c48feae7895fe916a35da,
title = "Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions",
abstract = "BACKGROUND: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95{\%} confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2{\%} (95{\%} CI, 83.7 to 92.6) as compared with 64.1{\%} (95{\%} CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8{\%} of patients in the venetoclax-obinutuzumab group and in 48.1{\%} of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5{\%} and 15.0{\%}, respectively. All-cause mortality was 9.3{\%} in the venetoclax-obinutuzumab group and 7.9{\%} in the chlorambucil-obinutuzumab group. These differences were not significant.CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).",
keywords = "Aged, Antibodies, Monoclonal, Humanized/administration & dosage, Antineoplastic Agents, Immunological/administration & dosage, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Bridged Bicyclo Compounds, Heterocyclic/administration & dosage, Chlorambucil/administration & dosage, Comorbidity, Female, Humans, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy, Male, Progression-Free Survival, Sulfonamides/administration & dosage",
author = "Kirsten Fischer and Othman Al-Sawaf and Jasmin Bahlo and Anna-Maria Fink and Maneesh Tandon and Mark Dixon and Sandra Robrecht and Simon Warburton and Kathryn Humphrey and Olga Samoylova and Liberati, {Anna M} and Javier Pinilla-Ibarz and Stephen Opat and Liliya Sivcheva and {Le D{\^u}}, Katell and Fogliatto, {Laura M} and Niemann, {Carsten U} and Robert Weinkove and Sue Robinson and Kipps, {Thomas J} and Sebastian Boettcher and Eugen Tausch and Rod Humerickhouse and Barbara Eichhorst and Clemens-Martin Wendtner and Langerak, {Anton W} and Karl-Anton Kreuzer and Matthias Ritgen and Valentin Goede and Stephan Stilgenbauer and Mehrdad Mobasher and Michael Hallek",
note = "Copyright {\circledC} 2019 Massachusetts Medical Society.",
year = "2019",
month = "6",
day = "6",
doi = "10.1056/NEJMoa1815281",
language = "English",
volume = "380",
pages = "2225--2236",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "23",

}

RIS

TY - JOUR

T1 - Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions

AU - Fischer, Kirsten

AU - Al-Sawaf, Othman

AU - Bahlo, Jasmin

AU - Fink, Anna-Maria

AU - Tandon, Maneesh

AU - Dixon, Mark

AU - Robrecht, Sandra

AU - Warburton, Simon

AU - Humphrey, Kathryn

AU - Samoylova, Olga

AU - Liberati, Anna M

AU - Pinilla-Ibarz, Javier

AU - Opat, Stephen

AU - Sivcheva, Liliya

AU - Le Dû, Katell

AU - Fogliatto, Laura M

AU - Niemann, Carsten U

AU - Weinkove, Robert

AU - Robinson, Sue

AU - Kipps, Thomas J

AU - Boettcher, Sebastian

AU - Tausch, Eugen

AU - Humerickhouse, Rod

AU - Eichhorst, Barbara

AU - Wendtner, Clemens-Martin

AU - Langerak, Anton W

AU - Kreuzer, Karl-Anton

AU - Ritgen, Matthias

AU - Goede, Valentin

AU - Stilgenbauer, Stephan

AU - Mobasher, Mehrdad

AU - Hallek, Michael

N1 - Copyright © 2019 Massachusetts Medical Society.

PY - 2019/6/6

Y1 - 2019/6/6

N2 - BACKGROUND: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax-obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant.CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).

AB - BACKGROUND: The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known.METHODS: In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated.RESULTS: In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax-obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant.CONCLUSIONS: Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).

KW - Aged

KW - Antibodies, Monoclonal, Humanized/administration & dosage

KW - Antineoplastic Agents, Immunological/administration & dosage

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Bridged Bicyclo Compounds, Heterocyclic/administration & dosage

KW - Chlorambucil/administration & dosage

KW - Comorbidity

KW - Female

KW - Humans

KW - Kaplan-Meier Estimate

KW - Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy

KW - Male

KW - Progression-Free Survival

KW - Sulfonamides/administration & dosage

U2 - 10.1056/NEJMoa1815281

DO - 10.1056/NEJMoa1815281

M3 - Journal article

VL - 380

SP - 2225

EP - 2236

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -

ID: 57444084