Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience
Venetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-04-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2024.1370405/full |
| _version_ | 1827287437735362560 |
|---|---|
| author | Francesco Angotzi Federica Lessi Matteo Leoncin Carla Filì Mauro Endri Albana Lico Andrea Visentin Stefano Pravato Anna Candoni Livio Trentin Carmela Gurrieri |
| author_facet | Francesco Angotzi Federica Lessi Matteo Leoncin Carla Filì Mauro Endri Albana Lico Andrea Visentin Stefano Pravato Anna Candoni Livio Trentin Carmela Gurrieri |
| author_sort | Francesco Angotzi |
| collection | DOAJ |
| description | Venetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The aim of the current study was to retrospectively outline the safety profile, response and survival outcomes of R/R AML patients treated with VEN in association with HMAs. Clinical, biological, and molecular data were collected from 57 patients with R/R AML treated with VEN combined with azacitidine or decitabine between 2018 and 2023. The median age of patients was 63 years, 38 (66.7%) received treatment for relapsed disease while 19 (33.3%) for refractory disease, 5 (8.7%) were treated for molecular relapse. A consistent proportion of the cohort was represented by patients with unfavorable prognostic factors such as complex karyotype (36.8%), secondary AML (29.8%), previous exposure to HMAs (38.6%), and relapse after allogeneic stem cell transplant (22.8%). A total of 14 patients achieved CR (24.6%), 3 (5.3%) CRi, 3 (5.3%) MLFS, and 3 (5.3%) PR, accounting for an ORR of 40.4%. The CR/CRi rate was higher in the group treated with azacitidine than in the group treated with decitabine (37.8% vs. 15%). The median OS was 8.2 months, reaching 20.1 months among responding patients. VEN-HMAs treatment allowed to bridge to allogeneic stem cell transplantation 11 (23.9%) of eligible patients, for which a median OS of 19.8 months was shown. On multivariate analysis, ECOG performance status ≥2, complex karyotype and not proceeding to allogeneic stem cell transplantation after therapy with VEN-HMAs were the factors independently associated with shorter OS. Patients treated with the azacitidine rather than the decitabine containing regimen generally displayed a trend toward superior outcomes. The major toxicities were prolonged neutropenia and infections. In conclusion, this study showed how VEN-HMAs could represent an effective salvage therapy in patients with R/R AML, even among some of those patients harboring dismal prognostic features, with a good toxicity profile. Further prospective studies are thus warranted. |
| first_indexed | 2024-04-24T10:58:12Z |
| format | Article |
| id | doaj.art-1dc19f49a1674f73b8dadeba5d415a59 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-24T10:58:12Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1dc19f49a1674f73b8dadeba5d415a592024-04-12T04:27:47ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-04-011410.3389/fonc.2024.13704051370405Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experienceFrancesco Angotzi0Federica Lessi1Matteo Leoncin2Carla Filì3Mauro Endri4Albana Lico5Andrea Visentin6Stefano Pravato7Anna Candoni8Livio Trentin9Carmela Gurrieri10Hematology Unit, Azienda Ospedale-Università and University of Padova, Padua, ItalyHematology Unit, Azienda Ospedale-Università and University of Padova, Padua, ItalyHematology Unit, Azienda Ulss3 Serenissima, Ospedale dell’Angelo, Venice, ItalyDivision of Hematology and Bone Marrow Transplantation, Azienda Sanitaria Universitaria Integrata Friuli Centrale (ASUFC), Udine, ItalyHematology Section, Dipartimento di Medicina Specialistica, Ca’ Foncello Hospital, Treviso, ItalyHematology and Cell Therapy Division, San Bortolo Hospital, Vicenza, ItalyHematology Unit, Azienda Ospedale-Università and University of Padova, Padua, ItalyHematology Unit, Azienda Ospedale-Università and University of Padova, Padua, ItalyDivision of Hematology and Bone Marrow Transplantation, Azienda Sanitaria Universitaria Integrata Friuli Centrale (ASUFC), Udine, ItalyHematology Unit, Azienda Ospedale-Università and University of Padova, Padua, ItalyHematology Unit, Azienda Ospedale-Università and University of Padova, Padua, ItalyVenetoclax (VEN) has been shown to play a synergistic effect in combination with hypomethylating agents (HMAs) in the frontline treatment of acute myeloid leukemia (AML). However, the potential role of this therapy in the relapsed/refractory (R/R) AML setting, still needs to be further unveiled. The aim of the current study was to retrospectively outline the safety profile, response and survival outcomes of R/R AML patients treated with VEN in association with HMAs. Clinical, biological, and molecular data were collected from 57 patients with R/R AML treated with VEN combined with azacitidine or decitabine between 2018 and 2023. The median age of patients was 63 years, 38 (66.7%) received treatment for relapsed disease while 19 (33.3%) for refractory disease, 5 (8.7%) were treated for molecular relapse. A consistent proportion of the cohort was represented by patients with unfavorable prognostic factors such as complex karyotype (36.8%), secondary AML (29.8%), previous exposure to HMAs (38.6%), and relapse after allogeneic stem cell transplant (22.8%). A total of 14 patients achieved CR (24.6%), 3 (5.3%) CRi, 3 (5.3%) MLFS, and 3 (5.3%) PR, accounting for an ORR of 40.4%. The CR/CRi rate was higher in the group treated with azacitidine than in the group treated with decitabine (37.8% vs. 15%). The median OS was 8.2 months, reaching 20.1 months among responding patients. VEN-HMAs treatment allowed to bridge to allogeneic stem cell transplantation 11 (23.9%) of eligible patients, for which a median OS of 19.8 months was shown. On multivariate analysis, ECOG performance status ≥2, complex karyotype and not proceeding to allogeneic stem cell transplantation after therapy with VEN-HMAs were the factors independently associated with shorter OS. Patients treated with the azacitidine rather than the decitabine containing regimen generally displayed a trend toward superior outcomes. The major toxicities were prolonged neutropenia and infections. In conclusion, this study showed how VEN-HMAs could represent an effective salvage therapy in patients with R/R AML, even among some of those patients harboring dismal prognostic features, with a good toxicity profile. Further prospective studies are thus warranted.https://www.frontiersin.org/articles/10.3389/fonc.2024.1370405/fullacute myeloid leukemiavenetoclaxhypomethylating agentsazacitidinedecitabinerelapsed/refractory acute myeloid leukemia |
| spellingShingle | Francesco Angotzi Federica Lessi Matteo Leoncin Carla Filì Mauro Endri Albana Lico Andrea Visentin Stefano Pravato Anna Candoni Livio Trentin Carmela Gurrieri Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience Frontiers in Oncology acute myeloid leukemia venetoclax hypomethylating agents azacitidine decitabine relapsed/refractory acute myeloid leukemia |
| title | Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience |
| title_full | Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience |
| title_fullStr | Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience |
| title_full_unstemmed | Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience |
| title_short | Efficacy and safety of venetoclax plus hypomethylating agents in relapsed/refractory acute myeloid leukemia: a multicenter real-life experience |
| title_sort | efficacy and safety of venetoclax plus hypomethylating agents in relapsed refractory acute myeloid leukemia a multicenter real life experience |
| topic | acute myeloid leukemia venetoclax hypomethylating agents azacitidine decitabine relapsed/refractory acute myeloid leukemia |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1370405/full |
| work_keys_str_mv | AT francescoangotzi efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT federicalessi efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT matteoleoncin efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT carlafili efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT mauroendri efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT albanalico efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT andreavisentin efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT stefanopravato efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT annacandoni efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT liviotrentin efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience AT carmelagurrieri efficacyandsafetyofvenetoclaxplushypomethylatingagentsinrelapsedrefractoryacutemyeloidleukemiaamulticenterreallifeexperience |