Maintenance Therapy for Multiple Myeloma After an Autologous Transplant: What Have We Learned?

Abstract

1 ISSN 2045-1393 10.2217/IJH.13.70 © 2014 Future Medicine Ltd Int. J. Hematol. Oncol. (2014) 3(1), 1–3 Current treatment for newly diagnosed multiple myeloma (MM) can be divided into different phases: induction, highdose chemotherapy and autologous hematopoietic stem cell transplantation (autoHSCT), consolidation and maintenance. The use of auto-HSCT, immunomodulatory agents (IMiDs) and proteasome inhibitors (PIs) in the treatment of MM have greatly improved the progression-free survival (PFS) and overall survival (OS) of these patients in the last 10–15 years [1]. Even with recent progress in therapy, almost all MM patients eventually relapse. To overcome this problem, approaches such as post-auto-HSCT consolidation and maintenance are being explored to prolong the duration of remission and delay disease progression [2–4]. Maintenance therapy for MM is primarily used to prolong the remission duration and, hence, survival after induction therapy and/or auto-HSCT [5–7]. An ideal maintenance drug should be easy to administer, safe and well tolerated over prolonged periods, and improve OS. In this editorial, we will review the evolution and current status of maintenance therapy after auto-HSCT, and offer recommendations based on the available data. Prior to the availability of IMiDs and PIs, interferon and corticosteroids were used as maintenance therapy, mainly after induction, with modest benefit [8,9]. Their use was limited by significant toxicity and a high rate of discontinuation in the case of interferon [8]. After IMiDs and PIs became available, thalidomide, lenalidomide and bortezomib have been used for maintenance after an auto-HSCT. Thalidomide, with or without corticosteroids, has been used in post-autoHSCT maintenance in at least six randomized clinical trials thus far [4,10–14]. With the exception of the Canadian trial [4], the other five trials demonstrated an improvement in PFS; however, only two studies, IFM 99 [10] and the Australian study [12], demonstrated an improvement in OS. A meta-ana lysis of these trials by the International Myeloma Working Group (IMWG) confirmed an improvement in PFS (hazard ratio [HR]: 0.65), but concluded that the trials were too heterogeneous to confirm an OS benefit [7]. These trials differed in induction therapy, thalidomide dose and duration, and concurrent use of corticosteroids. In the IFM trial [10], benefit of thalidomide maintenance was restricted to patients with less than a very good partial response and