Universität zu Köln

Fischer, K., Al-Sawaf, O., Bahlo, J., Fink, A. -M., Tandon, M., Dixon, M., Robrecht, S., Warburton, S., Humphrey, K., Samoylova, O., Liberati, A. M., Pinilla-Ibarz, J., Opat, S., Sivcheva, L., Du, K. Le, Fogliatto, L. M., Niemann, C. U., Weinkove, R., Robinson, S., Kipps, T. J., Boettcher, S., Tausch, E., Humerickhouse, R., Eichhorst, B., Wendtner, C. -M., Langerak, A. W., Kreuzer, K. -A., Ritgen, M., Goede, V., Stilgenbauer, S., Mobasher, M. and Hallek, M. (2019). Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions. N. Engl. J. Med., 380 (23). S. 2225 - 2237. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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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.)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fischer, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Al-Sawaf, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bahlo, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, A. -M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tandon, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dixon, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robrecht, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Warburton, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Humphrey, K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Samoylova, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Liberati, A. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pinilla-Ibarz, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Opat, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sivcheva, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Du, K. Le UNSPECIFIED UNSPECIFIED UNSPECIFIED Fogliatto, L. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Niemann, C. U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weinkove, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Robinson, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kipps, T. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boettcher, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tausch, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Humerickhouse, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Eichhorst, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendtner, C. -M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Langerak, A. W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuzer, K. -A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ritgen, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goede, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stilgenbauer, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mobasher, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-138115
DOI:	10.1056/NEJMoa1815281
Journal or Publication Title:	N. Engl. J. Med.
Volume:	380
Number:	23
Page Range:	S. 2225 - 2237
Date:	2019
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHRONIC LYMPHOCYTIC-LEUKEMIA; IBRUTINIB; GUIDELINES Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13811