Bortezomib Based Induction Is Superior to Thalidomide Based Induction in Reducing Early Relapses Following Upfront HDM: an Analysis By the Asian Myeloma Working Group

Background: Multiple myeloma is a heterogeneous disease with certain genetic features associated with worse outcomes. The benefit of Bortezomib for high risk genetic patient subgroups remains unclear in an Asian population. We performed a retrospective analysis to compare bortezomib-based induction versus thalidomide-based induction in Asian patients who were treated with upfront autologous transplant.

Methods: We retrospectively analyzed outcomes of 240 patients who received autologous transplant in two centers in Singapore (n=167) and one center in Korea (n=73) after bortezomib-based (n=120) versus thalidomide-based induction (n=120) between 2006 and 2014. Patients were staged according to International Staging System (ISS), and responses were defined according to International Myeloma Working Group criteria. Early relapse was defined as relapse within 12 months post-transplant. High risk cytogenetics included the presence of 17p13 deletion, t(14;16), or t(4;14) by FISH.

Results: Baseline characteristics (age, gender, ISS, cytogenetics) were not significantly different between groups receiving bortezomib versus thalidomide induction. Bortezomib induction was associated with improved rates of complete response (CR) post-induction (40% vs 25%, p=0.013) and post-transplant (52% vs 48%, p=0.038). Median overall survival (OS) was prolonged with bortezomib (53 months vs 27 months, p=0.027). Multivariate analysis adjusted for baseline characteristics showed bortezomib reduced the risk of early relapse (HR 0.23, 95% CI 0.09-0.57, p=0.001), and improved overall survival (OS) (HR 0.2, 95% CI 041-0.93, p=0.021). Factors independently associated with poorer OS were high risk cytogenetics (HR 1.77, p=0.011), failure to achieve very good partial response (VGPR) or better post-induction (HR 1.70, p=0.005), early relapse (HR 6.20, p<0.001), but not advanced ISS stage or hypodiploidy karyotype. In subgroup analysis, patients with high-risk cytogenetics (n=46) who received bortezomib had improved OS (HR 0.39, CI 0.17 to 0.93, p=0.033), but patients with standard risk cytogenetics did not have significant OS benefit with bortezomib (HR 0.71, p=0.139).

Conclusion: Our results suggest that despite upfront autologous stem cell transplantation, patients benefit from bortezomib versus thalidomide induction. Furthermore, bortezomib may be beneficial in overcoming the adverse prognostic effect of high-risk cytogenetics.