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OVERALL SURVIVAL BENEFIT OF OBINUTUZUMAB OVER RITUXIMAB WHEN COMBINED WITH CHLORAMBUCIL IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA AND COMORBIDITIES: FINAL SURVIVAL ANALYSIS OF THE CLL11 STUDY
Author(s): ,
Valentin Goede
Affiliations:
German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology,University Hospital,Cologne,Germany;Oncogeriatric Unit, Department of Geriatric Medicine,St Marien Hospital,Cologne,Germany
,
Kirsten Fischer
Affiliations:
German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology,University Hospital,Cologne,Germany
,
Martin JS Dyer
Affiliations:
The Ernest and Helen Scott Haematological Research Institute,University of Leicester,Leicester,United Kingdom
,
Lothar Müller
Affiliations:
Oncology Practice,Leer,Germany
,
Lukas Smolej
Affiliations:
Charles University Faculty of Medicine,University Hospital,Hradec Králové,Czech Republic
,
Maria Chiara Di Bernardo
Affiliations:
On assignment to F. Hoffmann-La Roche Ltd,Basel,Switzerland
,
Andrea Knapp
Affiliations:
F. Hoffmann-La Roche Ltd,Basel,Switzerland
,
Tina Nielsen
Affiliations:
F. Hoffmann-La Roche Ltd,Basel,Switzerland
Michael Hallek
Affiliations:
German CLL Study Group, Department I of Internal Medicine, Center of Integrated Oncology,University Hospital,Cologne,Germany;Cologne Cluster of Excellence in Cellular Stress Responses in Aging-Associated Diseases,University of Cologne,Cologne,Germany
EHA Library. Goede V.
Jun 15, 2018; 215923
Topic: 3Aj Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Valentin Goede
Valentin Goede
Contributions
Abstract

Abstract: S151


Type: Presidential Symposium


Presentation during EHA23: On Friday, June 15, 2018 from 16:15 - 16:30


Location: Room A1


Background
Obinutuzumab (GA101; G), a glycoengineered type II anti-CD20 monoclonal antibody, has been developed as an effective treatment for chronic lymphocytic leukemia (CLL). The phase III CLL11 study evaluated the efficacy and safety of G plus chlorambucil (Clb; G-Clb) and rituximab (R) plus Clb (R-Clb) vs Clb alone (Stage 1), as well as G-Clb vs R-Clb (Stage 2), in patients with previously untreated CLL and comorbidities. Previous pre-planned analyses have established superiority of G-Clb over Clb alone and R-Clb. 


Aims
We report the final analysis of the CLL11 study (data cut-off, 10 October 2017), with approximately 2 years of additional follow-up compared with previous analyses. 


Methods
Patients were randomised 1:2:2 to receive six 28-day cycles (C) of Clb, R-Clb or G-Clb. Clb (0.5 mg/kg) was administered orally on Day (D) 1 and D15 of C1–6. R was administered intravenously (IV) at a dose of 375 mg/m2 on D1 of C1 and 500 mg/m2 on D1 of C2–6. G (1000 mg) was administered IV on D1 (dose split over two days; 100 mg D1, 900 mg D2), D8 and D15 of C1, and D1 of C2–6. Eligible patients had previously untreated CD20+ CLL, a total Cumulative Illness Rating Scale (CIRS) score of >6 and/or a creatinine clearance (CrCl) of <70 mL/min. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), time to new treatment (TTNT) and safety. Comparison of PFS was performed by log rank test. Treatment effects were expressed as hazard ratios (HR) using a stratified Cox regression model. 


Results
A total of 781 patients were enrolled and received treatment (median: age, 73 years; CIRS score, 8; CrCl, 62 mL/min). No new safety signals were identified at this update. After a median observation time of 62.5 months, treatment with G-Clb (n=238) was associated with improved outcomes compared with Clb alone (n=118); median: PFS, 31.1 vs 11.1 months (HR 0.21, 95% CI 0.16–0.28, p<0.0001); OS, not reached vs 66.7 months (HR 0.68, 95% CI 0.49–0.94, p=0.0196); and TTNT, 55.7 vs 15.1 months (HR 0.25, 95% CI 0.19–0.35, p<0.0001). After a median observation time of 59.4 months, G-Clb (n=333) also demonstrated a clinically meaningful improvement in outcomes compared with R-Clb (n=330); median: PFS, 28.9 vs 15.7 months (HR 0.49, 95% CI 0.41–0.58, p<0.0001) and TTNT, 56.4 vs 34.9 months (HR 0.58, 95% CI 0.46–0.73, p<0.0001) (Figure 1A and 1B). Notably, G-Clb also provided a clinically meaningful improvement in OS compared with R-Clb; median OS, not reached vs 73.1 months (HR 0.76, 95% CI 0.60–0.97, p=0.0245) (Figure 1C). Two- and five-year survival rates were 91% vs 84% and 66% vs 57% for G-Clb vs R-Clb, respectively. Overall, fewer patients died in the G-Clb arm (37%) than in the R-Clb arm (45%). During the survival follow-up period, the most common cause of death was disease progression (G-Clb, 10%; R-Clb, 15%).



Conclusion
This final survival analysis from the CLL11 study confirms that G-Clb provides clinically meaningful benefits in CLL patients with comorbidities, including prolongation of PFS and OS, when compared with R-Clb and Clb alone, and an absolute treatment-free duration of approximately four and a half years, while maintaining an acceptable and manageable safety profile. These findings support the use of G-Clb as first-line treatment for CLL patients with comorbidities, and suggest G as the preferred anti-CD20 antibody in future combination regimens for CLL. 


Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical




Keyword(s): Chronic Lymphocytic Leukemia, Obinutuzumab, Rituximab, Survival


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