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Published January 1, 2024 | Version v1
Journal article Open

In the era of Bortezomib-based Induction, intensification of Melphalan-based conditioning with Bortezomib does not improve Survival Outcomes in newly diagnosed Multiple Myeloma: a study from the Chronic Malignancies Working Party of the EBMT

Creators

  • 1. Istinye Univ, Hematol & Stem Cell Transplantat Unit, Ankara Liv Hosp, TR-06880 Ankara, Turkiye
  • 2. EBMT Stat Unit, Leiden, Netherlands
  • 3. EBMT Leiden Study Unit, Leiden, Netherlands
  • 4. CHU Bordeaux, Hop Haut Leveque, Pessac, France
  • 5. Clin Univ St Luc, Brussels, Belgium
  • 6. Ctr Pierre & Marie Curie, Algiers, Algeria
  • 7. Samodzielny Publ, Lublin, Poland
  • 8. Amer Univ Beirut, Bone Marrow Transplantat Program, Med Ctr, Beiruit, Lebanon
  • 9. Gazi Univ, Fac Med, Ankara, Turkiye
  • 10. Univ Hosp Bern, Bern, Switzerland
  • 11. Ctr Natl Greffe Moelle, Tunis, Tunisia
  • 12. Univ Freiburg, Freiburg, Germany
  • 13. Pavlov Univ, RM Gorbacheva Res Inst, St Petersburg, Russia
  • 14. Soochow Univ, Affiliated Hosp 1, Suzhou, Peoples R China
  • 15. Galway Univ Hosp, Blood & Tissue Estab, Galway, Ireland
  • 16. Univ Klinikum Jena, Jena, Germany
  • 17. Manchester Royal Infirm, Manchester, England
  • 18. Leiden Univ, Dept Biomed Data Sci, Med Ctr, Leiden, Netherlands
  • 19. Heidelberg Univ, Med Klin & Poliklin 5, Heidelberg, Germany
  • 20. Hop La Pitie Salpetriere, Hematobiol Dept, Paris, France

Description

Bortezomib (Vel)- Melphalan 200 mg/m2 (Mel200) (Vel-Mel) has been utilised to intensify conditioning in autologous hematopoietic stem cell transplantation (AHCT) for multiple myeloma (MM). This EBMT registry-based study compared Vel-Mel with Mel200 during upfront AHCT. Between 2010 and 2017, MM patients who received Vel-Mel (n = 292) conditioning were compared with 4,096 Mel200 patients in the same 58 centres. Pre-AHCT, compared to Mel200 patients, Vel-Mel patients had similar International Staging System (ISS) scores and cytogenetic risk profiles; a similar proportion had received bortezomib-based induction (85% and 87.3%, respectively) though they were younger with a better performance status. Vel-Mel patients were more likely to achieve CR post-induction (40.6% vs 20.3%, p < 0.001) and by day 100 of AHCT (CR/VGPR: 70.2 % vs. 57.2%, p < 0.001). There was no difference in 3-year PFS (49% vs 46%, p = 0.06) or early post-AHCT mortality. In multivariable analysis, Vel-Mel associated with inferior PFS (HR: 1.69 (1.27-2.25, p < 0.001) and OS (HR:1.46 (1.14-1.86,p = 0.002), similar to negative effects on PFS of advanced ISS (HR:1.56 (1.33-1.83, p < 0.001), high-risk cytogenetics (HR:1.43(1.18-1.74, p < 0.001) and poor post-induction response(<=PR)(HR: 1.43(1.25-1.62, p < 0.001) Overall, despite superior pre- and post-AHCT responses, there was no improvement in PFS or OS following Vel-Mel. This data supports the findings of the smaller prospective IFM study.

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