# Maintenance Strategies in High-Risk Myeloma: A Multicenter Comparison of Bortezomib–Lenalidomide Versus Lenalidomide Alone: A USMIRC Multicenter Analysis

## TL;DR

This study compares two maintenance therapies for high-risk multiple myeloma after stem cell transplants and finds no significant survival benefit from adding bortezomib to lenalidomide.

## Contribution

A multicenter real-world comparison of VR versus R maintenance in HRMM, highlighting the lack of significant efficacy improvement with the doublet regimen.

## Key findings

- VR maintenance showed numerically longer PFS compared to R alone, but the difference was not statistically significant.
- No treatment-related mortality occurred within 100 days post-transplant in either group.
- The study emphasizes the need for novel maintenance strategies in high-risk multiple myeloma.

## Abstract

Maintenance therapy plays a critical role in prolonging disease control and improving long-term outcomes in patients with high-risk multiple myeloma (HRMM). While lenalidomide maintenance following autologous stem cell transplantation (ASCT) has been shown to improve progression-free survival (PFS) and overall survival (OS) in multiple myeloma, these benefits are attenuated in patients with HRMM. Given that some centers employ doublet maintenance strategies despite the absence of a clearly established standard of care for HRMM, our multicenter analysis addresses an important gap in the current literature by comparing the efficacy and safety of doublet versus single-agent maintenance therapy, specifically bortezomib plus lenalidomide (VR) versus lenalidomide alone (R), in the post-transplant setting.

Background: Lenalidomide maintenance after autologous stem cell transplantation (ASCT) improves progression-free survival (PFS) and overall survival (OS) in multiple myeloma; however, these benefits are attenuated in high-risk multiple myeloma (HRMM). No standard post-transplant maintenance strategy is established for HRMM, and some centers employ doublet maintenance with bortezomib plus lenalidomide (VR). We evaluated outcomes with VR versus lenalidomide alone (R) in HRMM. Methods: We conducted a multicenter retrospective study through the US Myeloma Innovations Research Collaborative (USMIRC), including adults with HRMM who received R or VR maintenance following ASCT between January 2009 and January 2024. HRMM was defined by del(17p), t(4;14), t(14;16), or t(14;20), with or without 1q gain. PFS and OS were estimated using Kaplan–Meier methods. Median follow-up was 91 months. Baseline characteristics, induction regimens, and post-transplant response depth were well balanced between the groups. Median PFS was 51 months (95% CI, 20–NR) with VR and 36 months (95% CI, 31–56) with R (p > 0.05). Median OS was 103 months (95% CI, 90–NR) and 110 months (95% CI, 94–NR), respectively (p > 0.05). VR was associated with numerically longer PFS, although the difference was not statistically significant. No treatment-related mortality occurred within 100 days post-ASCT. Conclusions: In this multicenter real-world analysis of HRMM, VR maintenance did not result in statistically significant improvements in PFS or OS compared with lenalidomide alone. These findings underscore the need for prospective, risk-adapted trials incorporating novel maintenance strategies, including CD38- and BCMA-directed therapies, in high-risk disease.