CONTINUING REMISSIONS AFTER VENETOCLAX AND OBINUTUZUMAB IN PATIENTS WITH PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) AND COEXISTING MEDICAL CONDITIONS
Author(s): ,
Kirsten Fischer
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Othman Al-Sawaf
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Anna-Maria Fink
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Mark Dixon
Affiliations:
F. Hoffmann-La Roche Ltd,Welwyn Garden City,United Kingdom
,
Sandra Robrecht
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Jasmin Bahlo
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Maneesh Tandon
Affiliations:
F. Hoffmann-La Roche Ltd,Welwyn Garden City,United Kingdom
,
Simon Warburton
Affiliations:
F. Hoffmann-La Roche Ltd,Welwyn Garden City,United Kingdom
,
Thomas J. Kipps
Affiliations:
Moores Cancer Center, University of California San Diego,San Diego,United States
,
Robert Weinkove
Affiliations:
Wellington Blood and Cancer Centre, Capital and 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,Canada
,
Martin Dreyling
Affiliations:
Department of Internal Medicine III,University Hospital Ludwig-Maximilians University Munich,Munich,Germany
,
Stephen Opat
Affiliations:
Monash Hematology,Monash University,Clayton,Australia
,
Carolyn Owen
Affiliations:
Department of Hematology,Tom Baker Cancer Centre,Calgary,Canada
,
Javier López
Affiliations:
Hospital Ramon y Cajal,Madrid,Spain
,
Rod Humerickhouse
Affiliations:
AbbVie, Inc.,North Chicago,United States
,
Clemens-M Wendtner
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany;Department of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases and Tropical Medicine,Klinikum Schwabing,Munich,Germany
,
Karl-Anton Kreuzer
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Anton W. Langerak
Affiliations:
Department of Immunology, Laboratory for Medical Immunology,Erasmus Medical Center,Rotterdam,Netherlands
,
Jacque J.M. van Dongen
Affiliations:
Department of Immunology, Laboratory for Medical Immunology,Erasmus Medical Center,Rotterdam,Netherlands
,
Matthias Ritgen
Affiliations:
Second Department of Medicine,University Hospital of Schleswig-Holstein, Campus Kiel,Kiel,Germany
,
Sebastian Boettcher
Affiliations:
Second Department of Medicine,University Hospital of Schleswig-Holstein, Campus Kiel,Kiel,Germany;Department III of Internal Medicine,University Hospital Rostock,Rostock,Germany
,
Valentin Goede
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Barbara Eichhorst
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
,
Stephan Stilgenbauer
Affiliations:
Department of Internal Medicine III,Ulm University,Ulm,Germany
,
Mehrdad Mobasher
Affiliations:
Genentech, Inc.,South San Francisco,United States
Michael Hallek
Affiliations:
Department I of Internal Medicine,Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne,Cologne,Germany
EHA Library. Fischer K. Jun 15, 2018; 214822; PF349
Kirsten Fischer
Kirsten Fischer
Contributions
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Abstract

Abstract: PF349

Type: Poster Presentation

Presentation during EHA23: On Friday, June 15, 2018 from 17:30 - 19:00

Location: Poster area

Background

The combination of venetoclax and obinutuzumab was reported to achieve excellent responses regarding overall responses rates (ORR), complete responses (CR) and MRD-negativitiy with manageable toxicity in previously untreated patients with chronic lymphocytic leukemia (CLL).

Aims

The CLL14 trial is a prospective, open-label, multicenter, randomized phase-III trial to compare the efficacy and safety of obinutuzumab and venetoclax with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Prior to the randomized phase, a safety run-in phase was conducted. Here we present long-term follow-up results for safety and efficacy for patients treated within the run-in phase.

Methods
Thirteen previously untreated patients with confirmed CLL and with coexisting medical conditions assessed by cumulative illness rating scale (CIRS) total score >6 and/or estimated creatinine clearance (CrCl) <70 mL/min requiring treatment according to iwCLL criteria were enrolled. Treatment consisted of 6 cycles obinutuzumab and venetoclax followed by 6 cycles of venetoclax. Risk assessment for tumor lysis syndrome (TLS) was performed before treatment. Adverse events were graded per NCI CTCAE v.4. MRD in peripheral blood was assessed by ASO-PCR, flow cytometry and NGS. Progression free survival (PFS) was defined as the time between enrollment and first disease progression or death and overall survival (OS) as the time between enrollment and death.

Results
Baseline characteristics, acute toxicity and ORR of 100% three months after the end of treatment, were previously reported. As of this analysis, 12 patients had completed treatment and had at least 18 months of follow-up. One patient discontinued treatment early due to a grade 4 infusion-related reaction following the first infusion of obinutuzumab. Median observation time was 29.6 months (range 20.7-35.0). A total of 264 adverse events were reported for all 12 patients that had received obinutuzumab and venetoclax. Of these, 226 occurred during the treatment period, 27 during the first and 11 during the second year of follow-up period. No prolonged neutropenia was observed. A total of 35 infections were reported. One basal cell carcinoma, but no further secondary malignancies were reported. A 90 year old patient who was in CR died of cardiac failure nine months after the end of treatment, which was assessed as non-related by the investigator. Median PFS and OS have not been reached. At month 30, 80.2% of the patients were progression-free and 92.3% were alive (Figure 1A, 1B). At follow-up month 3, 11 of 12 treated patients had no detectable (<10-4) minimal residual disease by ASO-PCR in peripheral blood and one patient was assessed positive (≥10-4). At follow-up month 18, seven patients remained MRD negative and four patients were assessed positive. MRD results assessed by flow cytometry are shown in Figure 1C.

Conclusion

The combination of venetoclax and obinutuzumab in previously untreated patients with CLL appears to induce long-lasting remissions. The trial population consists of 13 elderly patients (median age 75 years) with clinically meaningful comorbidities in addition to CLL including 2 patients with deletion 17p. After the fixed treatment duration of 12 cycles and with median follow-up of 30 months, 80.2% of patients are progression-free and 12 patients are still alive.

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

Keyword(s): BCL2, Chronic Lymphocytic Leukemia, Obinutuzumab, Treatment

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