Outcomes of Bortezomib Maintenance Compared with Lenalidomide Maintenance in Patients with High-Risk Multiple Myeloma and Chronic Kidney Disease Undergoing Autologous Stem Cell Transplant

Background: Patients with high-risk multiple myeloma (HRMM) are associated with poorer outcomes following autologous stem cell transplant (ASCT). Lenalidomide is currently the standard of care for maintenance therapy following ASCT as it has been associated with improved progression-free survival (PFS) and overall survival (OS). Recent studies have explored utilizing other agents for maintenance therapy including proteasome inhibitors – bortezomib. In the HOVON trial (EudraCT no. 2004‐000944‐26), inclusion of bortezomib in maintenance therapy was associated with improved survival outcomes in patients with HRMM. However, in a recent study (Bumma et al, 2023), researchers found no superior outcomes in HRMM patients who received bortezomib compared to patients who received lenalidomide alone. A few reports have linked lenalidomide to renal dysfunction, whereas bortezomib has not been as strongly associated with nephrotoxicity. With this in mind, we sought to further elucidate whether there was a difference in survival outcomes between bortezomib and lenalidomide maintenance therapy in HRMM post-ASCT in regard to patients’ chronic kidney disease (CKD) status.

Methods: We sought out patients with HRMM who were undergoing ASCT within 12 months of diagnosis from January 2013 to December 2018 after receiving triplet induction in the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Overall, we identified 164 patients with HRMM that fit our subpopulation of interest of patients with CKD stage 3-5 who received lenalidomide or bortezomib maintenance therapy. HRMM was defined as patients with cytogenetic features including at least one of the following: t(4:14), t(14:16), t(14:20), deletion at 17p, and abnormality at 1q, Hazard ratios (HR) were calculated comparing patients’ non-relapse mortality (NRM), relapse, progression-free survival (PFS), and overall survival (OS) for patients with HRM who received bortezomib as maintenance therapy compared to lenalidomide.

Results: There were 126 patients in the lenalidomide group and 38 patients in the bortezomib group. Various baseline characteristics between the two groups were compared. The only characteristic in which the groups significantly differed was sex; the bortezomib group was 34.8% female, while the lenalidomide group was 42.1% female. Notably, there was no significant difference between the makeup of high-risk cytogenetic abnormalities between the two groups. Patients with bortezomib maintenance therapy demonstrated worse outcome in terms of 1-year relapse with adjusted odds ratio (OR) of 0.33 (95% CI 0.13, 0.84; p-value 0.020). However, this difference was not seen when looking at 2-year relapse. The lenalidomide group also demonstrated improvement in OS when compared to the bortezomib group. Patients with CKD Stage 3-5 who received lenalidomide maintenance therapy showed improvement in OS at both 1- and 2-year intervals with survival of 98.4% at 1-year and 91.9% at 2-year, compared to 94.7% and 78.4% at 1 and 2 years respectively in the bortezomib group. This improvement in OS with the lenalidomide group was significant with HR of 0.34 (95% CI 0.12, 0.94; p-value 0.037)

Conclusions: Lenalidomide maintenance therapy demonstrated superior outcomes when compared to the bortezomib maintenance therapy with HRMM and CKD Stage 3-5. These findings contrast with recent studies showing improved survival outcomes in patients with HRMM who received bortezomib maintenance therapy. These results corroborate the continued use of lenalidomide for maintenance therapy even in patients with baseline kidney disease. There is a need for prospective randomized clinical trials regarding post-transplant maintenance therapy for HRMM.