Immune and cellular determinants of response to HMA-venetoclax regimens in acute myeloid leukemia - Summary - MDSpire
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Immune and Cellular Factors Shaping Response to Hypomethylating Agent–Venetoclax Therapy in Acute Myeloid Leukemia

  • By

  • Alfredo Marchetti

  • Francesca Lazzaroni

  • Matteo Claudio Da Via'

  • Marta Lionetti

  • Giulia Maggioni

  • Alessia Campagna

  • Denise Ventura

  • Giorgio A. Croci

  • Alessio Marella

  • Akihiro Maeda

  • Antonio Matera

  • Emanuele Calvi

  • Margherita Scopetti

  • Filippo Viviani

  • Nicolò Rampi

  • Davide Bonometti

  • Elena Benzoni

  • Manuela Zappa

  • Sonia Fabris

  • Marzia Barbieri

  • Stefania Pioggia

  • Claudia Leoni

  • Antony Ricchiuti

  • Matteo G. D. Porta

  • Mariarita Sciumè

  • Francesco Passamonti

  • Nicola S. Fracchiolla

  • Niccolò Bolli

  • October 13, 2026

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Objective:

To examine molecular and immune features associated with response to hypomethylating agent–venetoclax (HMA-Ven) therapy, focusing on early treatment timepoints.

Approach:
  • Retrospective cohort: Clinical outcomes were assessed in 132 patients with AML treated with HMA-Ven; genomic profiling was available for 99 patients.
  • Single-cell analysis: Bone marrow samples from 10 patients with newly diagnosed de novo AML were profiled at diagnosis and after cycle one using single-cell RNA sequencing and T-cell receptor sequencing.
  • Response groups: Patients were classified as responders (CR/CRi), early relapse after an initial response, or refractory; early relapse and refractory cases were combined for non-responder comparisons.
Key Findings:
  • The cohort included newly diagnosed and relapsed/refractory AML; 65 patients received HMA-Ven as first-line therapy and 67 received it in later treatment lines.
  • Among 99 genomically profiled patients, the most frequent mutations were TET2 (29%), DNMT3A (27%), NPM1 (22%), and ASXL1 (20%). TP53, FLT3, IDH2, and NRAS mutations each occurred in 17%.
  • Median follow-up at the survival-analysis update was 17.06 months.
Interpretation:

The study used complementary cohort-level genomic profiling and early-treatment single-cell analyses to investigate factors associated with HMA-Ven response. The supplied context does not report the single-cell results or the survival comparison outcome.

Limitations:
  • Single-cell transcriptomic profiling was performed in only 10 patients, all with newly diagnosed de novo AML.
  • Genomic profiling was available for 99 of 132 patients.
  • The retrospective cohort included patients treated in both first-line and later-line settings.

Original Source(s)

Immune and cellular determinants of response to HMA-venetoclax regimens in acute myeloid leukemia

  • by Alfredo Marchetti, Francesca Lazzaroni, Matteo Claudio Da Via', Marta Lionetti, Giulia Maggioni, Alessia Campagna, Denise Ventura, Giorgio A. Croci, Alessio Marella, Akihiro Maeda, Antonio Matera, Emanuele Calvi, Margherita Scopetti, Filippo Viviani, Nicolò Rampi, Davide Bonometti, Elena Benzoni, Manuela Zappa, Sonia Fabris, Marzia Barbieri, Stefania Pioggia, Claudia Leoni, Antony Ricchiuti, Matteo G. D. Porta, Mariarita Sciumè, Francesco Passamonti, Nicola S. Fracchiolla, Niccolò Bolli

  • October 13, 2026

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