Risk adapted post-transplant maintenance in multiple myeloma

ABSTRACT

Introduction: The survival of multiple myeloma patients is increasing due to new medications, the widespread implementation of autologous stem cell transplantation and better supportive treatments. The controversy surrounding post-transplant treatment is debated due to a lack of large randomized trials comparing the different treatment modalities. The questions for each proposed treatment are whether it improves outcomes, has low cumulative toxicities and is easy to administer.

Areas covered: In this review, we have summarized the current data on maintenance therapy in newly diagnosed MM patients undergoing ASCT, focusing on bortezomib, thalidomide and lenalidomide as well as newer agents

Expert opinion: Maintenance treatment has been shown to deepen and prolong responses and increase PFS and OS. Lenalidomide is approved for maintenance and guidelines recommend its use post ASCT. Ixazomib has recently been reported to improve PFS.

KEYWORDS:

• Maintenance therapy
• multiple myeloma
• risk-adapted
• bortezomib
• thalidomide
• lenalidomide

Article Highlights

• When considering any drug for maintenance treatment, one should take into account the route of administration, potential cumulative toxicities and expected outcome benefits.

• Maintenance treatment in NDMM after ASCT has been proved to prolong PFS and OS and deepen the responses.

• The standard of care for maintenance treatment in NDMM after ASCT is lenalidomide. There is evidence that this might be more suitable for standard risk patients, and bortezomib might be more appropriate for high risk patients.

• Thalidomide maintenance treatment showed improved PFS but its use has been reduced due to its long term toxicities and the shorter OS in high risk patients.

• Open questions include the duration of treatment, the role of combination treatments and the role of the newer agents.

• There are not enough data to justify the use of consolidation therapy after ASCT.

Declaration of interest

M Gertz reports personal fees from Ionis/Akcea, Alnylam, Prothena, Celgene, Janssen, Annexon, Appellis, Amgen, Medscape, Physicians Education Resource, Research to Practice, as well as personal fees for Data Safety Monitoring board from Abbvie and grants and personal fees from Spectrum. M Gertz has received speaker fees from Teva, Johnson and Johnson, Medscape, DAVA oncology. M Gertz serves on advisory boards for Pharmacyclics and for Proclara outside the submitted work. M Gertz receives royalties from Springer Publishing, as well as grant funding from the Amyloidosis Foundation and International Waldenstrom Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest 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 that they serve as an advisor to Fujimoto Pharmaceutical Company Japan. Another reviewer has disclosed that they have receive research support from Amgen, Bristol-Myers Squibb, Celgene, Chugai, Janssen, Sanofi, Mundipharma, Takeda and Novartis and serve on advisory boards at:Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Sanofi and Takeda. They have also received honoraria from: ArtTempi, Bristol-Myers Squibb, Celgene, Chugai, Janssen and Novartis. Another reviewer has disclosed that they have received research study funding from Seattle Genetics, Millennium-Takeda, Sanofi-Genzyme, Merck Sharpe and Dohme Inc. They have also received royalty from Up-To-Date and act as a consultant to Jazz Pharmaceuticals and National Comprehensive Cancer Network. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was partially funded by NCI SPORE MM SPORE 5P50 CA186781-04.