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

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.

The risk and survival of multiple myeloma as the second primary malignancy in a single Chinese center

“…The introduction of new drugs, including proteasome inhibitors and immunomodulators, has significantly improved the prognosis of patients with MM. Since the survival of patients with MM, in general, is increasing ( 35 , 36 ), SPM accounts for an increasing proportion of the overall cancer burden ( 37 ). The exact underlying biological mechanism remains unclear and may be related to genetic susceptibility, non-genetic related factors (such as age), and treatment-related factors.…”