Richard F Schlenk1, Carsten Müller-Tidow, Axel Benner, Meinhard Kieser. 1. aNCT-Trial Center, German Cancer Research Center bDepartment of Hematology and Oncology, University of Heidelberg cDivision of Biostatistics, German Cancer Research Center dInstitute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Abstract
PURPOSE OF REVIEW: Aim of this review was to focus on prognostic and predictive factors, standard and new treatment approaches, and on statistical considerations for future clinical trials in patients with relapsed/refractory acute myeloid leukemia (r/r-AML). RECENT FINDINGS: New prognostic molecular markers were identified in r/r-AML, FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations. Intensive combination chemotherapy including gemtuzumab ozogamicin emerged as an effective salvage therapy in refractory AML. Timing of allo-HCT in r/r-AML may be oriented at the probability to achieve a response to intensive salvage therapy. Several new treatment approaches ranging from new and modified cytotoxic drugs to targeted approaches are in clinical development with first efficacy assessment in single-arm phase II studies. Their external validity may be considerably increased by using a novel design based on a matching approach. SUMMARY: FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations are identified as prognostic molecular markers in r/r-AML. Timing of allo-HCT should be based on the probability to achieve a response to intensive salvage therapy. Several new approaches are currently evaluated and matching for controls may help to increase external validity.
PURPOSE OF REVIEW: Aim of this review was to focus on prognostic and predictive factors, standard and new treatment approaches, and on statistical considerations for future clinical trials in patients with relapsed/refractory acute myeloid leukemia (r/r-AML). RECENT FINDINGS: New prognostic molecular markers were identified in r/r-AML, FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations. Intensive combination chemotherapy including gemtuzumab ozogamicin emerged as an effective salvage therapy in refractory AML. Timing of allo-HCT in r/r-AML may be oriented at the probability to achieve a response to intensive salvage therapy. Several new treatment approaches ranging from new and modified cytotoxic drugs to targeted approaches are in clinical development with first efficacy assessment in single-arm phase II studies. Their external validity may be considerably increased by using a novel design based on a matching approach. SUMMARY:FLT3-ITD, mutated IDH1, and biallelic CEBPA mutations are identified as prognostic molecular markers in r/r-AML. Timing of allo-HCT should be based on the probability to achieve a response to intensive salvage therapy. Several new approaches are currently evaluated and matching for controls may help to increase external validity.
Authors: Richard F Schlenk; Jürgen Krauter; Emmanuel Raffoux; Karl-Anton Kreuzer; Markus Schaich; Lucien Noens; Thomas Pabst; Madhuri Vusirikala; Didier Bouscary; Andrew Spencer; Anna Candoni; Jorge Sierra Gil; Noah Berkowitz; Hans-Jochen Weber; Oliver Ottmann Journal: Haematologica Date: 2017-10-19 Impact factor: 9.941
Authors: Abhishek Maiti; Courtney D DiNardo; Wei Qiao; Tapan M Kadia; Elias J Jabbour; Caitlin R Rausch; Naval G Daver; Nicholas J Short; Gautam Borthakur; Naveen Pemmaraju; Musa Yilmaz; Yesid Alvarado; Kathryn S Montalbano; Allison Wade; Rita E Maduike; Julio A Guerrero; Kenneth Vaughan; Carol A Bivins; Sherry Pierce; Jing Ning; Farhad Ravandi; Hagop M Kantarjian; Marina Y Konopleva Journal: Cancer Date: 2021-08-03 Impact factor: 6.860
Authors: Fatih M Uckun; Christopher R Cogle; Tara L Lin; Sanjive Qazi; Vuong N Trieu; Gary Schiller; Justin M Watts Journal: Cancers (Basel) Date: 2019-12-26 Impact factor: 6.639