Association of response endpoints with survival outcomes in multiple myeloma

• Authors: Sagar Lonial, Emory University; KC Anderson, Harvard University
• Journal Title: Leukemia
• Volume: Volume 28, Number 2
• Publisher: Nature Publishing Group: Open Access Hybrid Model Option B | 2014-02, Pages 258-268
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/leu.2013.220
• Subjects: Health Sciences, Oncology
• Keywords: myeloma; depth of response; durability of response; survival; minimal residual disease; multidrug treatment

Abstract

Since the introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, more patients with multiple myeloma are achieving deep, durable responses and disease control, and are living longer. These improvements have afforded more robust analyses of the relationship between response and survival. Generally, these studies have demonstrated that improvements in the quality of response across all stages of treatment are associated with better disease control and longer survival. Thus, achievement of maximal response should be strongly considered, particularly in the frontline setting, but must also be balanced with tolerability, quality of life and patient preferences. In select patients, achievement of a lesser response may be adequate to prolong survival, and attempts to treat these patients to a deeper response may place them at unnecessary risk without significant benefit. Maintenance therapy has been shown to improve the quality of response and disease control and, in some studies, survival. Studies support maintenance therapy for high-risk patients as a standard of care, and there are emerging data supporting maintenance therapy in standard-risk patients to improve progression-free and possibly overall survival. Multidrug regimens combining a proteasome inhibitor and an IMiD have shown exceptional response outcomes with acceptable increases in toxicity in both the frontline and salvage settings, and are becoming a standard treatment approach. Moving forward, the use of immunophenotypic and molecular response criteria will be essential in better understanding the impact of highly active and continuous treatment regimens across myeloma patient populations. Future translational studies will help to develop antimyeloma agents to their fullest potential. The introduction of novel targeted therapies, including the IMiD pomalidomide and the proteasome inhibitors carfilzomib and ixazomib (MLN9708), will provide greater options to individualize treatment and help patients achieve a clinically meaningful response. Keywords: myeloma; depth of response; durability of response; survival; minimal residual disease; multidrug treatment