Hypomethylating Agents and Venetoclax for Acute Myeloid Leukemia Relapsed After Hematopoietic Stem Cell Transplant
Copyright © 2024 Elsevier Inc. All rights reserved..
BACKGROUND: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment.
PATIENTS AND METHODS: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi.
RESULTS: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle.
CONCLUSION: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Clinical lymphoma, myeloma & leukemia - (2024) vom: 12. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ionescu, Filip [VerfasserIn] |
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| Links: |
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| Themen: |
Azacitidine |
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| Anmerkungen: |
Date Revised 01.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.clml.2024.02.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369190971 |
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| 100 | 1 | |a Ionescu, Filip |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hypomethylating Agents and Venetoclax for Acute Myeloid Leukemia Relapsed After Hematopoietic Stem Cell Transplant |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment | ||
| 520 | |a PATIENTS AND METHODS: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival. We leveraged our larger sample to analyze the impact of cytogenetic/molecular features on the odds of CR/CRi | ||
| 520 | |a RESULTS: CR/CRi was achieved among 32 of 67 (48%) patients, and MRD negativity was recorded among 10 of 12. NPM1 and IDH 1 or 2 mutations increased the odds of CR/CRi, as did increasing time from alloHCT to relapse. Fourteen patients subsequently received donor lymphocyte infusions or a second alloHCT. Responses lasted a median of 17.8 months (95% CI, 7.2 months to not reached), and responders had a greater median overall survival of 19.7 months (95% CI, 7.6-51.5 months) compared to 2.9 months among nonresponders (95% CI, 1.8-4.4 months; log-rank P < .01). Treatment was well tolerated, but prolonged cytopenias were common and most patients required reduction in the number of venetoclax days per cycle | ||
| 520 | |a CONCLUSION: These data support the efficacy of this combination in the alloHCT relapse setting where we report responses among nearly half of patients, with possibly greater benefit for NPM1 and IDH 1/2-mutated cases. These responses can be durable and profound as evidenced by conversion to MRD negativity | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Azacitidine | |
| 650 | 4 | |a Decitabine | |
| 650 | 4 | |a Hematopoietic transplant | |
| 650 | 4 | |a Venetoclax | |
| 700 | 1 | |a David, Jerel C |e verfasserin |4 aut | |
| 700 | 1 | |a Ravichandran, Apoorva |e verfasserin |4 aut | |
| 700 | 1 | |a Sallman, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Sweet, Kendra |e verfasserin |4 aut | |
| 700 | 1 | |a Komrokji, Rami S |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Onyee |e verfasserin |4 aut | |
| 700 | 1 | |a Kuykendall, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Padron, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Faramand, Rawan |e verfasserin |4 aut | |
| 700 | 1 | |a Bejanyan, Nelli |e verfasserin |4 aut | |
| 700 | 1 | |a Khimani, Farhad |e verfasserin |4 aut | |
| 700 | 1 | |a Elmariah, Hany |e verfasserin |4 aut | |
| 700 | 1 | |a Pidala, Joseph |e verfasserin |4 aut | |
| 700 | 1 | |a Mishra, Asmita |e verfasserin |4 aut | |
| 700 | 1 | |a Perez, Lia |e verfasserin |4 aut | |
| 700 | 1 | |a Nishihori, Taiga |e verfasserin |4 aut | |
| 700 | 1 | |a Lancet, Jeffrey E |e verfasserin |4 aut | |
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