Venetoclax-based salvage therapy as 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 BCL2-inhibitor Venetoclax (VEN) in combination with hypomethylating agents (HMA) has been approved for first-line treatment of acute myeloid leukemai (AML) patients ineligible for intensive treatment. Emerging Data suggest that VEN containing treatment strategies may also be effective in relapsed/refractory (R/R) AML, however, comparative studies with conventional treatment strategies for medically fit patients as a bridge-to transplant strategy are limited. Using propensity score matching (PSM) analysis, we compared 37 R/R AML patients, who received VEN-based salvage therapy as bridge to allogeneic hematopoietic cell transplantation (allo-HCT) with 90 patients from the German Study Alliance Leukemia (SAL) AML registry, who were treated with non-VEN-containing salvage therapy according to their treating physician's choice (TPC) including intensive and non-intensive protocols. The overall response rate (ORR=CR+CRi) among all VEN patients was significantly higher compared to the TPC control cohort (62% vs. 42%; p=0.049). Overall, 73% of VEN-treated patients vs. 63% of TPC patients were successfully bridged to allo-HCT (p =0.41). After a median follow-up of 34.3 months for the VEN cohort and 21.0 months for the TPC cohort, the median overall-survival (OS) was 15.8 months (95%-CI, 10.6-NE) and 10.5 months (95%-CI, 6.8-19.6) (p=0.15), respectively. PSM revealed a trend towards improved OS for VEN patients (HR 0.70; 95%-CI, 0.41-1.22; p=0.20). Median event free survival (EFS) was significantly longer in the VEN cohort (8.0 months) compared to the TPC cohort (3.7 months) (p=0.006). In summary, our data suggests 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
JournalBlood advances
Publication statusE-pub ahead of print - 18 Sept 2024
Peer-reviewedYes

Keywords