Venetoclax-based salvage therapy as a bridge to transplant is feasible and effective in patients with relapsed/refractory AML

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Julia Marie Unglaub - , University Hospital Heidelberg (Author)
  • Richard F Schlenk - , National Center for Tumor Diseases (NCT) Dresden (Author)
  • Jan M Middeke - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Stefan W Krause - , University Hospital at the Friedrich-Alexander University Erlangen-Nürnberg (Author)
  • Sabrina Kraus - , University Hospital of Würzburg (Author)
  • Hermann Einsele - , University Hospital of Würzburg (Author)
  • Michael Kramer - , AvenCell Europe GmbH (Author)
  • Sven Zukunft - , Department of Internal Medicine I, University Hospital Carl Gustav Carus Dresden (Author)
  • Joseph Kauer - , University Hospital Heidelberg (Author)
  • Simon Renders - , German Cancer Research Center (DKFZ) (Author)
  • Elena Katelari - , University Hospital Heidelberg (Author)
  • Christoph Schliemann - , University Hospital Münster (Author)
  • Caroline Pabst - , University Hospital Heidelberg (Author)
  • Thomas Luft - , University Hospital Heidelberg (Author)
  • Peter Dreger - , Heidelberg University  (Author)
  • Christoph Röllig - , Department of Internal Medicine I, TUD Dresden University of Technology (Author)
  • Martin Bornhäuser - , Department of Internal Medicine I, National Center for Tumor Diseases Dresden (NCT/UCC), University Hospital Carl Gustav Carus Dresden (Author)
  • Carsten Müller-Tidow - , University Hospital Heidelberg (Author)
  • Tim Sauer - , University Hospital Heidelberg (Author)

Abstract

The B-cell lymphoma 2 inhibitor venetoclax (VEN) in combination with hypomethylating agents has been approved for first-line treatment of patients with acute myeloid leukemia (AML) ineligible for intensive treatment. VEN-containing treatment strategies may also be effective in relapsed/refractory (R/R) AML; however, comparative studies with conventional therapies for fit patients as a bridge-to-transplant strategy are limited. Using propensity score matching (PSM), we compared 37 patients with R/R AML, who received VEN-based salvage therapy as bridge to allogeneic hematopoietic stem cell transplantation (allo-HCT), with 90 patients from the German Study Alliance Leukemia AML registry, who were treated with non-VEN-containing salvage therapy according to their treating physician's choice (TPC). The overall response rate among VEN patients was higher than the TPC control cohort (62% vs 42%; P = .049). Overall, 73% of VEN-treated patients vs 63% of TPC patients were bridged to allo-HCT (P = .41). After a median follow-up of 34.3 months for the VEN and 21.0 months for the TPC cohort, the median overall survival (OS) were 15.8 months (95% confidence interval [CI], 10.6 to not evaluable) and 10.5 months (95% CI, 6.8-19.6; P = .15), respectively. PSM revealed a trend toward improved OS for VEN patients (hazard ratio, 0.70; 95% CI, 0.41-1.22; P = .20). Median event-free survival was significantly longer in the VEN cohort (8.0 months) than the TPC cohort (3.7 months; P = .006). Our data suggest that VEN-based salvage therapy is a safe and effective bridge to allo-HCT for this difficult-to-treat AML patient population.

Details

Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalBlood advances
Volume9
Issue number2
Publication statusE-pub ahead of print - 18 Sept 2024
Peer-reviewedYes

External IDs

unpaywall 10.1182/bloodadvances.2024013086
Scopus 85216469361
Mendeley 14ac513a-8d0b-3633-b295-ee8e0a9d90e0

Keywords

Keywords

  • Recurrence, Humans, Salvage Therapy/methods, Middle Aged, Antineoplastic Agents/therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute/therapy, Male, Treatment Outcome, Drug Resistance, Neoplasm, Sulfonamides/therapeutic use, Bridged Bicyclo Compounds, Heterocyclic/therapeutic use, Female, Adult, Aged