Literature DB >> 34322294

Hypomethylating agents+venetoclax induction therapy in acute myeloid leukemia unfit for intensive chemotherapy - novel avenues for lesser venetoclax duration and patients with baseline infections from a developing country.

Sumeet Mirgh1, Archana Sharma2,1, Mohammad Rizwan Mohammad Anwar Shaikh2,1, Kirti Kadian2,1, Narendra Agrawal2,1, Vishvdeep Khushoo2,1, Pallavi Mehta2,1, Rayaz Ahmed2,1, Dinesh Bhurani2,1.   

Abstract

Both elderly acute myeloid leukemia (AML) patients and those with baseline infections, when treated with intensive chemotherapy, are associated with high induction mortality. We report 24 patients (16-newly-diagnosed, 8-relapsed/refractory) with AML deemed unfit for intensive chemotherapy (by virtue of age >60 years, ECOG-PS 3-4, or those with non-resolving infections at baseline), treated with azacytidine-venetoclax combination as induction chemotherapy. Median follow-up of the study group was 8 months. The overall complete remission (CR)+CR with incomplete count recovery (CRi) rate was 58.3%. 1-year progression-free survival and overall survival of the whole cohort was 44.4% and 55.8%, respectively. On subgroup analysis, newly-diagnosed AML (p=0.05), intermediate-risk cytogenetics (p=0.007), and HMA-naïve (p=0.05) patients had a significantly better outcome. AML patients with baseline infections (versus without infections) treated with azacytidine-venetoclax induction, have lesser induction mortality (compared with historic intensive chemotherapy) with equivalent response rates. A detailed analysis amongst cohorts with different venetoclax durations revealed that, shorter duration (<21 days) venetoclax (versus 21-28 days duration) in induction therapy leads to similar response rates and similar severity of myelosuppression, however, with early count recovery and lesser duration of intravenous antibiotics. AJBR
Copyright © 2021.

Entities:  

Keywords:  Acute myeloid leukemia; India; azacytidine; elderly; infections; intensive chemotherapy; venetoclax duration

Year:  2021        PMID: 34322294      PMCID: PMC8303019     

Source DB:  PubMed          Journal:  Am J Blood Res        ISSN: 2160-1992


  24 in total

1.  Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on a new tool for therapy decision making.

Authors:  F Ferrara; G Barosi; A Venditti; E Angelucci; M Gobbi; F Pane; P Tosi; P Zinzani; S Tura
Journal:  Leukemia       Date:  2013-04       Impact factor: 11.528

Review 2.  Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

Authors:  Hartmut Döhner; Elihu Estey; David Grimwade; Sergio Amadori; Frederick R Appelbaum; Thomas Büchner; Hervé Dombret; Benjamin L Ebert; Pierre Fenaux; Richard A Larson; Ross L Levine; Francesco Lo-Coco; Tomoki Naoe; Dietger Niederwieser; Gert J Ossenkoppele; Miguel Sanz; Jorge Sierra; Martin S Tallman; Hwei-Fang Tien; Andrew H Wei; Bob Löwenberg; Clara D Bloomfield
Journal:  Blood       Date:  2016-11-28       Impact factor: 22.113

3.  Venetoclax with azacitidine disrupts energy metabolism and targets leukemia stem cells in patients with acute myeloid leukemia.

Authors:  Daniel A Pollyea; Brett M Stevens; Courtney L Jones; Amanda Winters; Shanshan Pei; Mohammad Minhajuddin; Angelo D'Alessandro; Rachel Culp-Hill; Kent A Riemondy; Austin E Gillen; Jay R Hesselberth; Diana Abbott; Derek Schatz; Jonathan A Gutman; Enkhtsetseg Purev; Clayton Smith; Craig T Jordan
Journal:  Nat Med       Date:  2018-11-12       Impact factor: 53.440

4.  Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia.

Authors:  Amanda C Winters; Jonathan A Gutman; Enkhtsetseg Purev; Molly Nakic; Jennifer Tobin; Stephanie Chase; Jeff Kaiser; Lindsey Lyle; Chelsey Boggs; Keri Halsema; Jeffrey T Schowinsky; Julie Rosser; Mark D Ewalt; Bradford Siegele; Vishal Rana; Steven Schuster; Diana Abbott; Brett M Stevens; Craig T Jordan; Clayton Smith; Daniel A Pollyea
Journal:  Blood Adv       Date:  2019-10-22

5.  Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia.

Authors:  Hagop M Kantarjian; Xavier G Thomas; Anna Dmoszynska; Agnieszka Wierzbowska; Grzegorz Mazur; Jiri Mayer; Jyh-Pyng Gau; Wen-Chien Chou; Rena Buckstein; Jaroslav Cermak; Ching-Yuan Kuo; Albert Oriol; Farhad Ravandi; Stefan Faderl; Jacques Delaunay; Daniel Lysák; Mark Minden; Christopher Arthur
Journal:  J Clin Oncol       Date:  2012-06-11       Impact factor: 44.544

6.  International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts.

Authors:  Hervé Dombret; John F Seymour; Aleksandra Butrym; Agnieszka Wierzbowska; Dominik Selleslag; Jun Ho Jang; Rajat Kumar; James Cavenagh; Andre C Schuh; Anna Candoni; Christian Récher; Irwindeep Sandhu; Teresa Bernal del Castillo; Haifa Kathrin Al-Ali; Giovanni Martinelli; Jose Falantes; Richard Noppeney; Richard M Stone; Mark D Minden; Heidi McIntyre; Steve Songer; Lela M Lucy; C L Beach; Hartmut Döhner
Journal:  Blood       Date:  2015-05-18       Impact factor: 22.113

7.  BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells.

Authors:  Eleni D Lagadinou; Alexander Sach; Kevin Callahan; Randall M Rossi; Sarah J Neering; Mohammad Minhajuddin; John M Ashton; Shanshan Pei; Valerie Grose; Kristen M O'Dwyer; Jane L Liesveld; Paul S Brookes; Michael W Becker; Craig T Jordan
Journal:  Cell Stem Cell       Date:  2013-01-17       Impact factor: 24.633

8.  Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial.

Authors:  Andrew H Wei; Pau Montesinos; Vladimir Ivanov; Courtney D DiNardo; Jan Novak; Kamel Laribi; Inho Kim; Don A Stevens; Walter Fiedler; Maria Pagoni; Olga Samoilova; Yu Hu; Achilles Anagnostopoulos; Julie Bergeron; Jing-Zhou Hou; Vidhya Murthy; Takahiro Yamauchi; Andrew McDonald; Brenda Chyla; Sathej Gopalakrishnan; Qi Jiang; Wellington Mendes; John Hayslip; Panayiotis Panayiotidis
Journal:  Blood       Date:  2020-06-11       Impact factor: 22.113

9.  Acute myeloid leukaemia: challenges and real world data from India.

Authors:  Chepsy Philip; Biju George; Abhijeet Ganapule; Anu Korula; Punit Jain; Ansu Abu Alex; Kavitha M Lakshmi; Usha Sitaram; Fouzia N Abubacker; Aby Abraham; Auro Viswabandya; Vivi M Srivastava; Alok Srivastava; Poonkuzhali Balasubramanian; Vikram Mathews
Journal:  Br J Haematol       Date:  2015-04-09       Impact factor: 6.998

10.  Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies.

Authors:  Courtney D DiNardo; Caitlin R Rausch; Christopher Benton; Tapan Kadia; Nitin Jain; Naveen Pemmaraju; Naval Daver; Wendy Covert; Kayleigh R Marx; Morgan Mace; Elias Jabbour; Jorge Cortes; Guillermo Garcia-Manero; Farhad Ravandi; Kapil N Bhalla; Hagop Kantarjian; Marina Konopleva
Journal:  Am J Hematol       Date:  2017-12-23       Impact factor: 13.265

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  1 in total

Review 1.  Venetoclax combined with hypomethylating agents or low-dose cytarabine as induction chemotherapy for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy: a systematic review and meta-analysis.

Authors:  Yao Qin; Pu Kuang; Ting Liu
Journal:  Clin Exp Med       Date:  2022-01-23       Impact factor: 3.984

  1 in total

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