-Author name in bold denotes the presenting author
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33 Real-World Experience of CPX-351 As First-Line Treatment in 188 Patients with Acute Myeloid LeukemiaClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 615. Acute Myeloid Leukemias: Commercially Available Therapies, Excluding Transplantation and Cellular Immunotherapies: Innovative induction regimens in AML: data from real life and clinical trials
Hematology Disease Topics & Pathways:
AML, Health Outcomes Research, Clinical Research, Diseases, Myeloid Malignancies
Saturday, December 11, 2021: 10:00 AM

Christina Rautenberg, MD1*, Friedrich Stölzel2*, Christoph Röllig, MD, MSC3*, Matthias Stelljes, MD4, Verena I Gaidzik, MD5, Michael Lauseker6*, Oliver Kriege, MD7*, Mareike Verbeek8*, Julia M. Unglaub, MD9*, Felicitas R Thol, MD10, Stefan W. Krause, MD11*, Mathias Haenel12,13*, Charlotte Neuerburg14*, Vladan Vucinic, MD15*, Christian Jehn16*, Julia Severmann17*, Maxi Wass, MD18*, Lars Fransecky, MD19*, Jens Chemnitz, MD20*, Udo Holtick, MD, PhD21*, Kerstin Schäfer-Eckart, MD22*, Josephine Schröder23*, Sabrina Kraus, MD24*, William Hermann Krüger, MD, PhD25*, Ulrich Kaiser26*, Sebastian Scholl, MD, PhD27*, Lea Henning28*, Guido Kobbe, MD29*, Rainer Haas, MD30*, Nael Alakel, MD31*, Maximilian Alexander Röhnert32*, Katja Sockel33*, Maher Hanoun, MD, PhD34*, Uwe Platzbecker, MD35*, Tobias A. W. Holderried, MD36*, Anke Morgner, MD13*, Michael Heuser, Prof., MD37*, Tim Sauer, MD38*, Katharina S. Goetze, MD39, Eva Maria Wagner, MD40, Konstanze Döhner, MD41, Hartmut Döhner, MD42, Christoph Schliemann, Prof., MD43*, Johannes Schetelig, MD, MSc44, Martin Bornhäuser, MD33*, Ulrich Germing, MD45*, Thomas Schroeder46 and Moritz Moritz Middeke, MD47*

1Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany
2Department of Internal Medicine I, University Hospital Carl Gustav Carus, TU Dre, Dresden, DEU
3Medical Department I, University Hospital, Dresden, Germany
4Department of Medicine A, Hematology, Oncology and Pneumology, University of Muenster, Muenster, Germany
5Internal Medicine III, Internal Medicine III, Ulm, Germany
6Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany
7Department of Hematology, Oncology, Pneumology, Medical Clinic III, UCT Johannes Gutenberg-University, Mainz, Germany
8Technische Universitaet Muenchen, Munich, DEU
9University Hospital Heidelberg, Heidelberg, Germany
10Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hanover, Germany
11Department of Hematology and Medical Oncology, University Hospital Erlangen, Erlangen, Germany
12Klinik für Innere Medizin III, KLINIKUM CHEMNITZ GGMBH, Chemnitz, Germany
13Klinikum Chemnitz, Chemnitz, Germany
14University Hospital Bonn, Bonn, Germany
15Clinic and Policlinic for Hematology and Cellular Therapy, University of Leipzig Medical Center, Leipzig, Germany
16Asklepios Hamburg, Hamburg, Germany
17University Hospital Essen, Essen, Germany
18Hematology and Oncology, University Hospital of Halle (Saale), Halle (Saale), Germany
19Klinik für Innere Medizin II, Universitätsklinikum Schleswig-Holstein, Kiel, Germany
20Gemeinschaftsklinikum Mittelrhein GmbH, Koblenz, Germany
21Department I of Internal Medicine, University of Cologne, Cologne, DEU
22Klinikum Nürnberg, Nürnberg, Germany
23Helios Berlin Buch, Berlin, Germany
24Department of Medicine II, University Hospital of Wuerzburg, Wuerzburg, Germany
25Universitätsmedizin Greifswald, Greifswald, Germany
26Bernward Krankenhaus, Bernward, Germany
27University Hospital Jena, Jena, Germany
28UK Essen, Essen, Germany
29Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
30Dept. of Hematology, Oncology and Clinical Immunology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
31University of Dresden, Dresden, DEU
32Department of Internal Medicine I, University Hospital Carl-Gustav-Carus Dresden, Dresden, Germany
33Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany
34Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany
35University of Leipzig Medical Center, Leipzig, Germany
36Department of Hematology, Oncology, Immunoncology and Rheumatology / Internal Medicine III, University Hospital Bonn, Bonn, Germany
37Department for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
38Internal Medicine V - Hematology, Oncology & Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
39Department of Medicine III, Technical University of Munich, Klinikum Rechts Der Isar, Munich, Germany
40University Hospital Mainz, Universitären Centrums für Tumorerkrankungen, Mainz, Germany
41University Hospital of Ulm, Ulm, Germany
42Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
43Department of Medicine A, Hematology, Oncology and Pneumology, University Hospital Muenster, Muenster, Germany
44Department of Internal Medicine I, University Hospital Dresden, Dresden, Germany
45University Hospital of Düsseldorf, Düsseldorf, Germany
46Hematology and Stem Cell Transplantation, Duisburg, Germany
47Medizinische Klinik I, Universitaetsklinikum C.G.Carus, Dresden, Germany

Background

In a recent phase-III trial CPX-351 (Jazz Pharmaceuticals, Palo Alto, CA), a liposomal encapsulation of cytarabine and daunorubicin, has shown higher remission rates and longer overall survival (OS) in patients aged 60 to 75 years with AML with myelodysplasia-related changes (AML-MRC) or therapy-related AML (t-AML) in comparison to conventional 7+3 regimen. Based on this CPX-351 has been approved in the USA 2017 and in Europe 2018 for adult patients with newly-diagnosed AML-MRC or t-AML. Still, several issues such as age (<60 years), measurable residual disease (MRD), molecular subgroups and outcome after allo-HCT were not addressed in the phase-III trial. Aiming to investigate these open aspects and to provide more clinical experience with CPX-351, we performed a real-world analysis of patients with AML treated with CPX-351 as first-line therapy.

Design/Methods:

For this retrospective analysis, we collected data on baseline characteristics, treatment details including allo-HCT and outcome from patients with newly-diagnosed AML-MRC or t-AML, who were treated with CPX-351 according to the EMA label between 2018 and 2020 in 25 German centers participating in the Study Alliance Leukemia (SAL), German Cooperative Transplant Study Group and the AML Study Group (AMLSG).

Results:

A total of 188 patients (median age 65 years, range 26 to 80) with t-AML (29%) or AML-MRC (70%) including 46 patients (24%) <60 years could be analyzed. Eigthy-six percent received one, 14% two induction cycles and 10% received consolidation with CPX-351. Following induction, CR/CRi rate was 47% including 64% of patients with available information achieving measurable residual disease (MRD) negativity (<10-3) as measured by flow cytometry at local laboratories. Additionally, 35 patients were categorized as MLFS at first remission control, which achieved CRi (n=16) or CR (n=10) in the further course without additional therapy. After median follow-up of 9.3 months, median overall survival (OS) was 21 months and 1-year OS rate was 64%. In multivariate analysis, complex karyotype predicted lower response (p=.0001), and pretreatment with hypomethylating agents (p=.02) and adverse European LeukemiaNet 2017 genetic risk (p<.0001) were associated with lower OS. Allo-HCT was performed in 116 patients (62%) including 101 of these patients with CR prior transplant and resulted in 1-year OS of 73% (median survival not reached), especially in MRD negative patients (p=.048). With 69% of patients developing grade III/IV non-hematologic toxicity following induction and a day 30-mortality of 8% the safety profile was consistent with previous findings.

Conclusion:

The results from this real-world analysis confirm CPX-351 as an efficient treatment for these high-risk AML patients bridging to facilitating allo-HCT in many patients with encouraging outcome after transplantation.

Disclosures: Röllig: Roche: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz: Honoraria; Janssen: Honoraria; Bristol-Meyer-Squibb: Honoraria, Research Funding; Amgen: Honoraria; AbbVie: Honoraria, Research Funding. Stelljes: Pfizer: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Medac: Speakers Bureau; Celgene/BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Kite/Gilead: Consultancy, Speakers Bureau. Gaidzik: Janssen: Speakers Bureau; Pfizer: Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Unglaub: Novartis: Consultancy, Other: travel costs/ conference fee; JazzPharma: Consultancy, Other: travel costs/ conference fee. Thol: Abbvie: Honoraria; Astellas: Honoraria; BMS/Celgene: Honoraria, Research Funding; Jazz: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Krause: Siemens: Research Funding; Takeda: Honoraria; Pfizer: Honoraria; art-tempi: Honoraria; Kosmas: Honoraria; Gilead: Other: travel support; Abbvie: Other: travel support. Haenel: Celgene: Consultancy, Honoraria; Amgen: Consultancy; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bayer Vital: Honoraria; Jazz: Consultancy, Honoraria; GSK: Consultancy. Vucinic: Novartis: Honoraria; Janssen: Honoraria, Other: Travel Sponsoring; Abbvie: Honoraria, Other: Travel Sponsoring; Gilead: Honoraria, Other: Travel Sponsoring; MSD: Honoraria. Fransecky: Novartis: Honoraria; Medac: Honoraria; Abbvie: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Holtick: Celgene: Honoraria; Sanofi: Honoraria. Kobbe: Celgene: Research Funding. Holderried: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Speakers Bureau; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; MSD: Speakers Bureau; Daiichi Sankyo: Other: travel support; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Therakos: Other: Travel support; Janssen: Other: Travel support; Abbvie: Other: Travel support; Eurocept Pharmaceuticals: Other: Travel support; Medac: Other: Travel support. Heuser: Astellas: Research Funding; Bayer AG: Honoraria, Research Funding; BMS/Celgene: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; BergenBio: Research Funding; Daichi Sankyo: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Roche: Research Funding; Tolremo: Honoraria; AbbVie: Honoraria; Janssen: Honoraria. Sauer: Pfizer: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Matterhorn Biosciences AG: Consultancy, Other: DSMB/SAB Member; Takeda: Consultancy, Other: DSMB/SAB Member. Goetze: Abbvie: Other: Advisory Board; BMS/Celgene: Other: Advisory Board, Research Funding. Döhner: Jazz Roche: Consultancy, Honoraria; Agios and Astex: Research Funding; Astellas: Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Honoraria, Other: Advisory Board; Daiichi Sankyo: Honoraria, Other: Advisory Board; Novartis: Consultancy, Honoraria, Research Funding; Celgene/BMS: Consultancy, Honoraria, Research Funding. Döhner: Jazz Pharmaceuticals: Honoraria, Research Funding; Agios: Honoraria, Research Funding; Pfizer: Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Honoraria; Helsinn: Honoraria; GEMoaB: Honoraria; Amgen: Honoraria, Research Funding; Astellas: Honoraria, Research Funding; Astex Pharmaceuticals: Honoraria; AstraZeneca: Honoraria; Berlin-Chemie: Honoraria; Oxford Biomedica: Honoraria; Roche: Honoraria. Schliemann: Philogen S.p.A.: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Other: travel grants; Astellas: Consultancy; AstraZeneca: Consultancy; Boehringer-Ingelheim: Research Funding; BMS: Consultancy, Other: travel grants; Jazz Pharmaceuticals: Consultancy, Research Funding; Novartis: Consultancy; Roche: Consultancy; Pfizer: Consultancy. Schetelig: Roche: Honoraria, Other: lecture fees; Novartis: Honoraria, Other: lecture fees; BMS: Honoraria, Other: lecture fees; Abbvie: Honoraria, Other: lecture fees; AstraZeneca: Honoraria, Other: lecture fees; Gilead: Honoraria, Other: lecture fees; Janssen: Honoraria, Other: lecture fees . Germing: Novartis: Honoraria, Research Funding; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding; Celgene: Honoraria; Jazz Pharmaceuticals: Honoraria. Schroeder: JAZZ: Honoraria, Research Funding.

*signifies non-member of ASH