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.

Beksac, Meral;Eikema, Diderik-Jan;Koster, Linda;Hulin, Cyrille;McLornan, Donal P;et.al.
(2024) Bone Marrow Transplantation — Vol. 59, n° 4, p. 526-533 (2024)

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  • Beksac, Meralorcid-logo
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  • Eikema, Diderik-Jan
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  • Koster, Linda
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  • Hulin, Cyrille
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  • Poire, Xavierorcid-logoUCLouvain
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  • McLornan, Donal Porcid-logo
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Abstract
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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Beksac, M., Eikema, D.-J., Koster, L., Hulin, C., Poire, X., Hamladji, R.-M., Gromek, T., Bazarbachi, A., Ozkurt, Z. N., Pabst, T., Ben Othman, T., Finke, J., Pirogova, O., Wu, D., Hayat, A., Hilgendorf, I., Tholouli, E., de Wreede, L. C., Schönland, S., et al. (2024). 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. Bone Marrow Transplantation, 59(4), 526-533. https://doi.org/10.1038/s41409-023-02160-8 (Original work published 2024)