Multiple Myeloma: Multiplying Therapies

Multiple myeloma must have among the most, if not the most, FDA approvals for any one malignancy. If the four liposomal doxorubicin approvals are counted separately, there are 21 FDA approvals (1). Such a list is remarkable and does not include combinations of these agents. The 5-year survival rates, which have almost doubled over the last decade, are now pegged at 48.5% and will likely be higher with the new agents approved by the FDA in 2015 (Fig. 1). Myeloma thus, represents a study in successful drug development, with paradigms that may be relevant for other malignancies. Over a decade has been spent in the development of targeted therapies for cancer, identifying unique targets and new agents, the foundation of “personalized medicine.” Yet, in myeloma, success has come not from unique targets but from therapies addressing plasma cell biology and from therapies with diverse consequences (i.e., the proteasome inhibitors and the immunomodulatory drugs, or “IMiDs”). We began to think, with imatinib in chronic myelogenous leukemia as the instructive example, that only one drug would be needed if we found the right target. But in myeloma, combinations have been the path to success, which is arguably a more applicable paradigm for other cancers. We have thought that progress against cancer would come from making it a “chronic disease,” but the data discussed in this CCR Focus suggest that the deeper the remission, the better the outcome. If that is true, then the old concept of fractional cell kill is still important in determining outcome, and the more cells we kill, the more likely we are to be successful. Finally, we still think of malignancy as a clonal disease, yet investigators studying myeloma have begun to see diverse simultaneous clones at the time of diagnosis, which is, again, a potential paradigm for other cancers. In this CCR Focus, Guest Editor Kenneth Anderson has brought together a group of experts to bring the progress in myeloma to life. It is perhaps fitting that Dr. Anderson would serve as Guest Editor for the final CCR Focus of 2016. He will soon step down from the position in which he has served, Editor-in-Chief for Clinical Cancer Research, for the last 9 years. During this time, he has led and participated in many of the advances in myeloma described in this CCR Focus. For the wider academic audience of Clinical Cancer Research, Dr. Anderson has been a source of encouragement and inspiration; for CCR Focus, his advocacy has ensured that it achieves its goal of bringing scholarly and accessible articles to interest both the expert and nonexpert reader of Clinical Cancer Research. We wish him well!

Susan E. Bates

Deputy Editor, CCR Focus

Columbia University Medical Center

See all articles in this CCR Focus section, “Multiple Myeloma: Multiplying Therapies.”