Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial.

Autor: Döhner H; Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany., Symeonidis A; Hematology Division, University Hospital, University of Patras Medical School, Patras, Greece., Deeren D; AZ Delta, Roeselare, Belgium., Demeter J; Semmelweis University, Budapest, Hungary., Sanz MA; Department of Hematology, University Hospital La Fe, Valencia, Spain., Anagnostopoulos A; Hematology Department, General Hospital G. Papanikolaou, Thessaloniki, Greece., Esteve J; Hospital Clinic de Barcelona, IDIBAPS, Barcelona, Spain., Fiedler W; Department of Medicine II, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany., Porkka K; Department of Hematology, Helsinki University Hospital Cancer Center, Helsinki, Finland., Kim HJ; Catholic Hematology Hospital, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea., Lee JH; Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea., Usuki K; NTT Medical Center Tokyo, Japan., D'Ardia S; A.O. Città della Salute e della Scienza, Torino, Italy., Won Jung C; Samsung Medical Center, Seoul, South Korea., Salamero O; Hospital Vall d'Hebron/VHIO/UAB-Medicine, Barcelona, Spain., Horst HA; UKSH Campus Kiel, Kiel, Germany., Recher C; Centre Hospitalier Universitaire de Toulouse, IUCT-Oncopole, Université Paul Sabatier Toulouse 3, Toulouse, France., Rousselot P; Centre Hospitalier de Versailles, University Versailles Saint-Quentin and Paris Saclay, Le Chesnay, France., Sandhu I; Division of Hematology, Department of Medicine, University of Alberta, Edmonton, AB, Canada., Theunissen K; Jessa Ziekenhuis, Hasselt, Belgium., Thol F; Medizinische Hochschule Hannover, Germany., Döhner K; Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany., Teleanu V; Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany., DeAngelo DJ; Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Naoe T; National Hospital Organization Nagoya Medical Center, Nagoya, Japan., Sekeres MA; Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA., Belsack V; SCS Boehringer Ingelheim Comm.V, Brussels, Belgium., Ge M; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut, USA., Taube T; Boehringer Ingelheim International GmbH, Biberach, Germany., Ottmann OG; Goethe University, Frankfurt/Main, Germany.
Jazyk: angličtina
Zdroj: HemaSphere [Hemasphere] 2021 Aug 02; Vol. 5 (8), pp. e617. Date of Electronic Publication: 2021 Aug 02 (Print Publication: 2021).
DOI: 10.1097/HS9.0000000000000617
Abstrakt: In this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1-10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized ≥5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95-2.89]; P = 0.071). At final analysis (≥574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8-1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections.
(Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)
Databáze: MEDLINE
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