FIXED-DURATION VENETOCLAX PLUS OBINUTUZUMAB IMPROVES PROGRESSION-FREE SURVIVAL AND MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH PREVIOUSLY UNTREATED CLL AND COMORBIDITIES
Author(s): ,
Kirsten Fischer
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Othman Al-Sawaf
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Jasmin Bahlo
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Anna-Maria Fink
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Maneesh Tandon
Affiliations:
Roche Products Limited,Welwyn Garden City,United Kingdom
,
Mark Dixon
Affiliations:
Roche Products Limited,Welwyn Garden City,United Kingdom
,
Sandra Robrecht
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Simon Warburton
Affiliations:
Roche Products Limited,Welwyn Garden City,United Kingdom
,
Kathryn Humphrey
Affiliations:
Roche Products Limited,Welwyn Garden City,United Kingdom
,
Olga Samoylova
Affiliations:
Regional Clinical Hospital N.A. Semashko,Nizhny Novgorod,Russian Federation
,
Anna Marina Liberati
Affiliations:
Division of Onco-Hematology, Santa Maria Terni Hospital,University of Perugia,Perugia,Italy
,
Javier Pinilla-Ibarz
Affiliations:
Department of Malignant Hematology,H. Lee Moffitt Cancer Center & Research Institute,Tampa, FL,United States
,
Stephen Opat
Affiliations:
Haematology Department, School of Clinical Sciences at Monash Health,Monash University,Victoria,Australia
,
Liliya Sivcheva
Affiliations:
First Internal Department,MHAT Hristo Botev, AD, Vrasta,Vratsa,Bulgaria
,
Katell Le Dû
Affiliations:
Hematology Department,Clinique Victor Hugo,Le Mans,France
,
Laura Maria Fogliatto
Affiliations:
Hospital de Clínicas de Porto Alegre,Porto Alegre,Brazil
,
Carsten Utoft Niemann
Affiliations:
Department of Hematology,Rigshospitalet, Copenhagen University Hospital,Copenhagen,Denmark
,
Robert Weinkove
Affiliations:
Wellington Blood & Cancer Centre,Capital & Coast District Health Board,Wellington,New Zealand;Malaghan Institute of Medical Research,Wellington,New Zealand
,
Sue Robinson
Affiliations:
Queen Elizabeth II Health Science Center,Halifax, NS,Canada
,
Thomas J. Kipps
Affiliations:
Moores Cancer Center,University of California San Diego,San Diego, CA,United States
,
Sebastian Boettcher
Affiliations:
Department III of Internal Medicine,University Hospital Rostock,Rostock,Germany
,
Eugen Tausch
Affiliations:
Department III of Internal Medicine,Ulm University,Ulm,Germany
,
William L. Schary
Affiliations:
AbbVie Inc,North Chicago, IL,United States
,
Barbara Eichhorst
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Clemens-Martin Wendtner
Affiliations:
Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine,Klinikum Schwabing,Munich,Germany
,
Anton W. Langerak
Affiliations:
Department of Immunology,Laboratory Medical Immunology, Erasmus MC,Rotterdam,Netherlands
,
Karl-Anton Kreuzer
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn,University Hospital,Cologne,Germany
,
Valentin Goede
Affiliations:
Oncogeriatric Unit, Dept. of Geriatric Medicine,St. Marien Hospital,Cologne,Germany
,
Stephan Stilgenbauer
Affiliations:
Department III of Internal Medicine,Ulm University,Ulm,Germany;Department for Hematology, Oncology and Rheumatology,Saarland University Medical School,Homburg/Saar,Germany
,
Mehrdad Mobasher
Affiliations:
Genentech Inc.,South San Francisco, CA,United States
,
Matthias Ritgen
Affiliations:
Department II of Internal Medicine, Campus Kiel,University of Schleswig-Holstein,Kiel,Germany
Michael Hallek
Affiliations:
Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital,CECAD (Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases), University of Cologne,Cologne,Germany
EHA Library. Fischer K. Jun 14, 2019; 267350; S149
Kirsten Fischer
Kirsten Fischer
Contributions
Abstract
This abstract is embargoed until Friday, June 14, 08:30 local time.

Abstract: S149

Type: Presidential Symposium

Presentation during EHA24: On Friday, June 14, 2019 from 16:45 - 17:00

Location: Hall 5

Background

The multinational, open-label, phase 3 CLL14 trial (NCT02242942) compared fixed-duration targeted venetoclax plus obinutuzumab (VenG) treatment with chlorambucil-obinutuzumab (ClbG) treatment in previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) and comorbidities.

Aims

We present endpoint analyses with particular emphasis on progression-free survival (PFS) and minimal residual disease (MRD)-negativity.

Methods

Pts with a CIRS score >6 and/or an estimated creatinine clearance <70 mL/min were randomized 1:1 to receive equal duration treatment with 12 cycles of standard Clb or Ven 400 mg daily in combination with G for the first 6 cycles. The primary endpoint was PFS. MRD-negativity in peripheral blood (PB) or bone marrow (BM) 3 months after treatment completion was a key secondary endpoint. MRD was analyzed serially from Cycle 4 every 3 months by an allele-specific oligonucleotide polymerase chain reaction assay (ASO-PCR; cut-off, 10-4) and by next generation sequencing (NGS; cut-offs, 10-4, 10-5, 10-6).

Results

In total, 432 pts were enrolled; 216 in each treatment group (intent-to-treat population). Median age, total CIRS score, and CrCl at baseline were 72 years, 8, and 66.4 ml/min respectively. After 29 months median follow-up, superior PFS was observed with VenG vs ClbG (Figure 1a). Median PFS was not reached in either group: at Month 24, PFS rates were 88% with VenG and 64% with ClbG (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.23–0.53; P<0.0001). MRD-negativity by ASO-PCR was significantly higher with VenG vs ClbG in both PB (76% vs 35% [P<0.0001]) and BM (57% vs 17% [P<0.0001]) 3 months after treatment completion. Overall, 75% of VenG MRD-negative pts in PB were also MRD-negative in BM vs 49% in the ClbG group. Landmark analysis for this timepoint by PB MRD status showed that MRD-negativity was associated with longer PFS. MRD-negativity rates were more sustainable with VenG: 81% (VenG) vs 27% (ClbG) of pts were MRD-negative 12 months after treatment completion; HR for MRD conversion 0.19; 95% CI 0.12–0.30 (median time off-treatment: 19 months) (Figure 1b). MRD-negativity rates by NGS confirmed these results; 78% (VenG) vs 34% (ClbG) of pts had MRD-negative status at <10-4, 35% vs 15% at ≥10-6–<10-5 and 31% vs 4% at <10-6, respectively.

Conclusion

Fixed-duration VenG induced deep, high (<10-4 in 3/4 of pts and <10-6 in 1/3 of pts), and long lasting MRD-negativity rates (with a low rate of conversion to MRD-positive status 1 year after treatment) in previously untreated pts with CLL and comorbidities, translating into improved PFS.

 

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

Keyword(s): BCL2, Chronic lymphocytic leukemia, Clinical trial, Minimal residual disease (MRD)

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