Shristi Upadhyay Banskota1, Nabin Khanal2, Rosalyn I Marar3, Prajwal Dhakal4, Vijaya Raj Bhatt5. 1. Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE, USA. 2. Division of Hematology and Oncology, Franciscan Health, Indianapolis, IN, USA. 3. Division of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. 4. Division of Hematology and Oncology, Blood and Marrow Transplantation Department of Internal Medicine, University of Iowa Health Care, Iowa City, IA, USA. 5. Division of Hematology and Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-6840, USA. vijaya.bhatt@unmc.edu.
Abstract
PURPOSE OF REVIEW: We review how understanding the fitness and comorbidity burden of patients, and molecular landscape of underlying acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the time of diagnosis is now integral to treatment. RECENT FINDINGS: The upfront identification of patients' fitness and molecular profile facilitates selection of targeted and novel agents, enables risk stratification, allows consideration of allogeneic hematopoietic cell transplantation in high-risk patients, and provides treatment selection for older (age ≥ 75) or otherwise unfit patients who may not tolerate conventional treatment. The use of measurable residual disease (MRD) assessment improves outcome prediction and can also guide therapeutic strategies such as chemotherapy maintenance and transplant. In recent years, several novel drugs have received FDA approval for treating patients with AML with or without specific mutations. A doublet and triplet combination of molecular targeted and other novel treatments have resulted in high response rates in early trials. Following the initial success in AML, novel drugs are undergoing clinical trials in MDS. Unprecedented advances have been made in precision medicine approaches in AML and MDS. However, lack of durable responses and long-term disease control in many patients still present significant challenges, which can only be met, to some extent, with innovative combination strategies throughout the course of treatment from induction to consolidation and maintenance.
PURPOSE OF REVIEW: We review how understanding the fitness and comorbidity burden of patients, and molecular landscape of underlying acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the time of diagnosis is now integral to treatment. RECENT FINDINGS: The upfront identification of patients' fitness and molecular profile facilitates selection of targeted and novel agents, enables risk stratification, allows consideration of allogeneic hematopoietic cell transplantation in high-risk patients, and provides treatment selection for older (age ≥ 75) or otherwise unfit patients who may not tolerate conventional treatment. The use of measurable residual disease (MRD) assessment improves outcome prediction and can also guide therapeutic strategies such as chemotherapy maintenance and transplant. In recent years, several novel drugs have received FDA approval for treating patients with AML with or without specific mutations. A doublet and triplet combination of molecular targeted and other novel treatments have resulted in high response rates in early trials. Following the initial success in AML, novel drugs are undergoing clinical trials in MDS. Unprecedented advances have been made in precision medicine approaches in AML and MDS. However, lack of durable responses and long-term disease control in many patients still present significant challenges, which can only be met, to some extent, with innovative combination strategies throughout the course of treatment from induction to consolidation and maintenance.
Authors: Elli Papaemmanuil; Moritz Gerstung; Hartmut Döhner; Peter J Campbell; Lars Bullinger; Verena I Gaidzik; Peter Paschka; Nicola D Roberts; Nicola E Potter; Michael Heuser; Felicitas Thol; Niccolo Bolli; Gunes Gundem; Peter Van Loo; Inigo Martincorena; Peter Ganly; Laura Mudie; Stuart McLaren; Sarah O'Meara; Keiran Raine; David R Jones; Jon W Teague; Adam P Butler; Mel F Greaves; Arnold Ganser; Konstanze Döhner; Richard F Schlenk Journal: N Engl J Med Date: 2016-06-09 Impact factor: 91.245
Authors: Richard F Schlenk; Sabine Kayser; Lars Bullinger; Guido Kobbe; Jochen Casper; Mark Ringhoffer; Gerhard Held; Peter Brossart; Michael Lübbert; Helmut R Salih; Thomas Kindler; Heinz A Horst; Gerald Wulf; David Nachbaur; Katharina Götze; Alexander Lamparter; Peter Paschka; Verena I Gaidzik; Veronica Teleanu; Daniela Späth; Axel Benner; Jürgen Krauter; Arnold Ganser; Hartmut Döhner; Konstanze Döhner Journal: Blood Date: 2014-09-30 Impact factor: 22.113
Authors: Richard M Stone; Sumithra J Mandrekar; Ben L Sanford; Kristina Laumann; Susan Geyer; Clara D Bloomfield; Christian Thiede; Thomas W Prior; Konstanze Döhner; Guido Marcucci; Francesco Lo-Coco; Rebecca B Klisovic; Andrew Wei; Jorge Sierra; Miguel A Sanz; Joseph M Brandwein; Theo de Witte; Dietger Niederwieser; Frederick R Appelbaum; Bruno C Medeiros; Martin S Tallman; Jürgen Krauter; Richard F Schlenk; Arnold Ganser; Hubert Serve; Gerhard Ehninger; Sergio Amadori; Richard A Larson; Hartmut Döhner Journal: N Engl J Med Date: 2017-06-23 Impact factor: 91.245
Authors: Prajwal Dhakal; Christopher S Wichman; Bunny Pozehl; Meaghann Weaver; Alfred L Fisher; Julie Vose; R Gregory Bociek; Vijaya R Bhatt Journal: Future Oncol Date: 2021-11-11 Impact factor: 3.674
Authors: Alexander E Perl; Giovanni Martinelli; Jorge E Cortes; Andreas Neubauer; Ellin Berman; Stefania Paolini; Pau Montesinos; Maria R Baer; Richard A Larson; Celalettin Ustun; Francesco Fabbiano; Harry P Erba; Antonio Di Stasi; Robert Stuart; Rebecca Olin; Margaret Kasner; Fabio Ciceri; Wen-Chien Chou; Nikolai Podoltsev; Christian Recher; Hisayuki Yokoyama; Naoko Hosono; Sung-Soo Yoon; Je-Hwan Lee; Timothy Pardee; Amir T Fathi; Chaofeng Liu; Nahla Hasabou; Xuan Liu; Erkut Bahceci; Mark J Levis Journal: N Engl J Med Date: 2019-10-31 Impact factor: 91.245