The era of lenalidomide maintenance therapy in multiple myeloma: settings for achieving best outcomes

ABSTRACT

Introduction

For patients with multiple myeloma who are eligible for high-dose melphalan therapy and autologous stem cell transplant (ASCT), the strategy of maintenance with low-dose lenalidomide therapy has become the current standard of care. However, this strategy is not curative, and many unanswered questions remain regarding the optimization of lenalidomide-based maintenance therapy.

Areas covered

In this review, we evaluate the current data supporting the use of lenalidomide maintenance, either alone or in combination, following ASCT. We provide an overview of the management of lenalidomide-associated toxicities as well as address the unresolved topics of optimal treatment duration and use of minimal residual disease assessment.

Expert opinion

While single-agent lenalidomide maintenance is a current standard of care, a one-size-fits-all approach to maintenance therapy is not optimal. The rapidly evolving landscape of multiple myeloma therapy in conjunction with ongoing clinical trials should enable a future where an individualized approach based on disease characteristics, response to induction and ASCT (or even non-ASCT consolidation approaches such as CAR T-cell therapy or bispecific antibodies), as well as patient preferences will influence the use of lenalidomide maintenance.

KEYWORDS:

• Autologous stem cell transplant
• lenalidomide
• maintenance
• multiple myeloma

Article highlights

• Four randomized phase 3 trials have demonstrated that lenalidomide maintenance after autologous stem cell transplant (ASCT) significantly prolongs progression. Meta-analyses have demonstrated an improvement in overall survival as well.

• The current recommendation is to continue lenalidomide until disease progression, however toxicities such as cytopenias and diarrhea can lead to early treatment discontinuation. Appropriate supportive care measures are recommended to limit these toxicities.

• Many studies are evaluating lenalidomide-based combination therapies in the post-ASCT maintenance setting, however the optimal combination has not yet been determined.

• The optimal maintenance strategy for patients with high-risk cytogenetics remains to be determined.

• Whether minimal residual disease (MRD) assessment can be used to determine the optimal duration of lenalidomide-based maintenance therapy is currently being evaluated.

Declaration of interest

SA Holstein has served as a consultant for BMS/Celgene, Genentech, GSK, Janssen, Oncopeptides, Sanofi, Secura Bio and Takeda; and has received research funding from Oncopeptides. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed receiving honoraria for lectures from Ono, Takeda, Janssen, Sanofi and Bristol Myers Squibb. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

Funding This paper was not funded.