The evolving role of maintenance therapy following autologous stem cell transplantation in multiple myeloma

ABSTRACT

Introduction: Maintenance therapy after autologous transplantation is a standard of care in newly diagnosed myeloma. However, there is no universal answer to the question of which maintenance strategy should be pursued after ASCT?

Areas covered: We conducted a MEDLINE search using the medical subject headings ‘multiple myeloma’, ‘autologous transplantation’ and ‘maintenance’ to identify available data from clinical trials on the role of different maintenance strategies after autologous transplantation for the newly diagnosed disease.

Expert opinion: A large meta-analysis demonstrated that lenalidomide prolongs progression-free and overall survival after autologous transplantation compared to observation/placebo. Further trials confirmed that lenalidomide maintenance increases rates of high-quality responses and one study demonstrated that lenalidomide maintenance improves outcomes regardless of cytogenetic risk. Although lenalidomide can cause side effects and is associated with an increased risk of second primary malignancies, its benefits outweigh the mentioned risks. The proteasome inhibitors ixazomib and bortezomib may partially overcome the negative effects of high-risk cytogenetics. Future trials will combine different agents and monoclonal antibodies during maintenance and will investigate whether minimal residual disease status can guide maintenance duration.

KEYWORDS:

• Autologous transplantation
• lenalidomide
• maintenance
• multiple myeloma

Article highlights

• Lenalidomide maintenance therapy prolongs PFS and OS after ASCT in NDMM and its benefits outweigh the risk of SPM.

• If tolerated, lenalidomide maintenance should be applied until disease progression at 15 mg/d.

• The proteasome inhibitors bortezomib and ixazomib are alternatives for patients who are unable to tolerate lenalidomide.

• Results from trials combining lenalidomide with monoclonal antibodies for maintenance therapy are still pending and might change the treatment landscape.

• MRD negativity might become a suitable endpoint in the upfront setting of ASCT and maintenance therapy, since it is highly correlated to OS.

Declaration of interest

Philip McCarthy has participated on the Advisory Boards for BMS, Celgene, Janssen, and Sanofi and has provided consultation for Karyopharm. McCarthy’s institute has also received research funding from Celgene. Sara Holstein has served as consultant or advisory board member for Adaptive Biotechnologies, Celgene, Genentech, GSK, Sorrento, and Takeda. Maximilian Merz has served on the advisory board and received travel grants from AMGEN and Takeda, has received research support from Takeda and also received a travel grant from Celgene. Jens Hillengass has received honoraria from Janssen, has served on the advisory board for AMGEN and Janssen and has received research support from Celgene. 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 previously worked with Takeda, Celgene, Janssen, and Ono. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The paper received no funding.