Moving toward individualized target-based therapies in acute myeloid leukemia

Bazinet, Alexandre; Kantarjian, Hagop

doi:10.1016/j.annonc.2022.11.004

Cited by 31 publications

(12 citation statements)

References 106 publications

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“…A PubMed search for these keywords in title or abstract yields over 33,000 results within the last 20 years. Personalized approaches can be found, for example, in treatment of certain forms of leukemia (Bazinet & Kantarjian, 2023) or in autoinflammatory diseases (Miner & Fitzgerald, 2023). In other fields, the importance of the individuality of behavior has been recognized as well: Even Drosophila shows idiosyncratic behavioral differences, which are caused by developmental variations in brain wiring rather than genetic factors (Linneweber et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

The elephant's other legs: What some sciences actually do

Baron

2024

Behav Brain Sci

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Integrative experiments, as described, seem blindly empirical, as if the question of generality of effects could not be understood through controlled one-at-a-time experiments. But current research using such experiments, especially applied research, can resolve issues and make progress through understanding of cause–effect pathways, leaving to engineers the task of translating this understanding into practice.

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Section: Introductionmentioning

confidence: 99%

The elephant's other legs: What some sciences actually do

Baron

2024

Behav Brain Sci

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“…Even if remission is achieved by chemotherapy, post-remission therapy has not been standardized [ 3 , 4 ]. Molecular target therapies for AML have been developed, but a problem of resistance emerges [ 5 ]. Thus, there is a need for immunotherapy that causes less physical stress and no-cross resistance to the above therapies.…”

Section: Introductionmentioning

confidence: 99%

Immunoreactivity to WT1 peptide vaccine is associated with prognosis in elderly patients with acute myeloid leukemia: follow-up study of randomized phase II trial of OCV-501, an HLA class II-binding WT1 polypeptide

Naoe

Saito

Hosono

et al. 2023

Cancer Immunol Immunother

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We previously conducted a randomized phase II trial of OCV-501, a WT1 peptide presented by helper T cells, in elderly AML (acute myeloid leukemia) patients in first remission, indicating no difference in 2-year disease-free survival (DSF) between the OCV-501 and placebo groups. Here, we analyzed 5-year outcome and biomarkers. Five-year DFS was 36.0% in the OCV-501 group (N = 52) and 33.7% in the placebo group (N = 53), with no significant difference (p = 0.74). The peripheral WT1 mRNA levels were marginally suppressed in the OCV-501 group compared with the placebo group. Enhanced anti-OCV-501 IgG response by the 25th week was an independent favorable prognostic factor. Anti-OCV-501 IFNγ responses were less frequent than the IgG reactions. These findings suggest that host immunoreactivity has a significant impact on the prognosis of AML and that further improvement of the WT1 peptide vaccine is needed.

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“…The addition of small molecule targeted therapies to intensive chemotherapy has also been investigated in newly diagnosed AML 1,2,24 . Sorafenib is an orally bioavailable multikinase inhibitor with efficacy against RAS/RAF , VEGF, C‐KIT , and FLT3 .…”

Section: Introductionmentioning

confidence: 99%

“…20,23 The addition of small molecule targeted therapies to intensive chemotherapy has also been investigated in newly diagnosed AML. 1,2,24 Sorafenib is an orally bioavailable multikinase inhibitor with efficacy against RAS/RAF, VEGF, C-KIT, and FLT3. The addition of sorafenib to standard induction chemotherapy in the SORAML trial resulted in significant improvements in event-free and relapse-free survival (RFS) in patients with newly diagnosed AML, regardless of FLT3 mutation status.…”

Section: Introductionmentioning

confidence: 99%

Phase II study of cladribine, idarubicin, and ara‐C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia

Kadia,

Ravandi,

Molica

et al. 2023

American J Hematol

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The addition of cladribine, or sorafenib to standard chemotherapy have each demonstrated improved survival in patients with newly‐diagnosed acute myeloid leukemia (AML). We studied the combination of cladribine, idarubicin, and intermediate‐dose cytarabine (CLIA) in patients ≤65 years of age with newly diagnosed AML, fit to receive intensive therapy. Cladribine (5 mg/m2) IV was administered on days (D)1–5, cytarabine (1 g/m2) on D1‐5, and idarubicin (10 mg/m2) on D1‐3. Sorafenib was added to the CLIA backbone for patients with FLT3‐ITD mutated AML. 80 patients were enrolled: 65 with newly diagnosed AML and 15 with AML arising from previously treated MDS (ts‐AML). The median age was 55 years (range, 21–65). CR + CRi was 83% (54/65) and 27% in the untreated and ts‐AML cohorts, respectively; 74% and 75% of responding patients, respectively, had undetectable measurable residual disease (MRD). Among patients with FLT3‐ITD mutated AML receiving CLIA+sorafenib, the CR + CRi rate was 95%, with 81% negative for MRD. With a median follow‐up of 76 months, the 2‐ and 4‐year OS of 57% and 50% compared to 20%, and 13% for ts‐AML, respectively. Patients treated with CLIA+sorafenib had 2‐ and 5‐year OS rates of 63% and 59%, respectively. The most common Grade ≥3 adverse events were infection/fever, elevated bilirubin, rash, and nausea. CLIA was safe and effective in young, fit patients with newly diagnosed AML with inferior outcomes among patients with ts‐AML. The addition of sorafenib to CLIA in FLT3‐ITD mutated AML resulted in high rates of durable remission and excellent long‐term survival.

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Moving toward individualized target-based therapies in acute myeloid leukemia

Cited by 31 publications

References 106 publications

The elephant's other legs: What some sciences actually do

The elephant's other legs: What some sciences actually do

Immunoreactivity to WT1 peptide vaccine is associated with prognosis in elderly patients with acute myeloid leukemia: follow-up study of randomized phase II trial of OCV-501, an HLA class II-binding WT1 polypeptide

Phase II study of cladribine, idarubicin, and ara‐C (CLIA) with or without sorafenib as initial therapy for patients with acute myeloid leukemia

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