2019 ASCO Annual Meeting!
Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
Type: Oral Abstract Session
Time: Tuesday June 4, 9:45 AM to 12:45 PM
Effect of fixed-duration venetoclax plus obinutuzumab (VenG) on progression-free survival (PFS), and rates and duration of minimal residual disease negativity (MRD–) in previously untreated patients (pts) with chronic lymphocytic leukemia (CLL) and comorbidities.
Chronic Lymphocytic Leukemia (CLL)
Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr 7502)
Author(s): Kirsten Fischer, Othman Al-Sawaf, Jasmin Bahlo, Anna-Maria Fink, Maneesh Tandon, Mark Dixon, Sandra Robrecht, Kathryn Humphrey, Sebastian Böttcher, Eugen Tausch, Rod Humerickhouse, Barbara Eichhorst, Clemens-Martin Wendtner, Anton W. Langerak, Karl-Anton Kreuzer, Valentin Goede, Stephan Stilgenbauer, Mehrdad Mobasher, Matthias Ritgen, Michael J. Hallek, CLL14 Study Investigators; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne, Germany; Roche Products Limited, Welwyn Garden City, United Kingdom; Department III of Internal Medicine, University Hospital Rostock, Rostock, Germany; Department III of Internal Medicine, Ulm University, Ulm, Germany; AbbVie Inc., North Chicago, IL; Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine, Klinikum Schwabing, Munich, Germany; Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, Netherlands; Oncogeriatric Unit, Dept. of Geriatric Medicine, St. Marien Hospital, Cologne, Germany; Department III of Internal Medicine, Ulm University, Ulm and Department for Hematology, Oncology and Rheumatology, Saarland University Medical School, Homburg/Saar, Germany; Genentech, Inc., South San Francisco, CA; Department II of Internal Medicine, Campus Kiel, University of Schleswig-Holstein, Kiel, Germany; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital, Cologne, CECAD (Cluster of Excellence on Cellular Stress Responses in Aging-Associated Diseases), University of Cologne, Cologne, Germany
Background: The multinational, open-label, phase 3 CLL14 trial compared fixed-duration targeted VenG treatment with chlorambucil-obinutuzumab (ClbG) in previously untreated pts with CLL and comorbidities. Here we present endpoint analyses with particular emphasis on MRD− and PFS. 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 (C) of standard Clb or Ven 400 mg daily in combination with G for first 6 C. Primary endpoint was PFS. MRD− in peripheral blood (PB) or bone marrow (BM) 3 months (mo) after treatment completion was a key secondary endpoint. MRD was analyzed serially from C4 every 3 mo 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: 432 pts were enrolled; 216 in each treatment group (intent-to-treat population). After 29 mo median follow-up, superior PFS was observed with VenG vs ClbG (HR 0.35; 95% CI 0.23–0.53; P<0.0001). MRD− 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 mo 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− was associated with longer PFS. Higher MRD− rates were achieved early and were more sustainable with VenG: 81% (VenG) vs 27% (ClbG) of pts were MRD-negative 12 mo after treatment completion; HR for MRD conversion 0.19; 95% CI 0.12–0.30 (median time off-treatment: 19 mo). MRD− rates by NGS confirmed these results; 78% (VenG) vs 34% (ClbG) of pts had MRD− at <10-4, 31% vs 4% at <10-6 and 35% vs 15% at ≥10-6–<10-5, respectively. Conclusions: Fixed-duration VenG induced deep (<10-6 in 1/3 of pts), high, and long lasting MRD− rates (with a low rate of conversion to MRD+ status 1 year after treatment) in previously untreated pts with CLL and comorbidities, translating into improved PFS. Clinical trial information: NCT02242942