Managing multiple myeloma: the emerging role of novel therapies and adapting combination treatment for higher risk settings

Abstract

Summary Novel therapies have transformed the treatment paradigm for multiple myeloma with significant improvements in survival now seen in both younger and older patients. Nonetheless, the disease is heterogeneous and high‐risk patients in particular continue to have poor outcome. Moreover, the disease remains incurable. Efforts to refine risk stratification and disease characteristics continue with the use of cytogenetics, enhanced imaging techniques and other new technologies, such as genomics. The integration of novel therapies into induction therapy, consolidation and maintenance continues to evolve, and the appropriate use of combination strategies including proteasome inhibition and immunomodulatory treatment is emerging as a platform with application across the disease spectrum. Despite these advances, resistance to novel agents occurs and so the identification of new targets and the recognition of clonal heterogeneity are especially important as improvements to current treatment strategies are developed, with the goal of further improving patient outcome.

Improvement in long-term outcomes with successive Total Therapy trials for multiple myeloma: are patients now being cured?

“…21–23 The myeloma community, at present, is divided between those advocating cure and others advocating disease control. 24 Randomized clinical trials are currently in progress to address this important issue, 25 although median follow-up needs to be in the 10-year range for meaningful conclusions to be derived.…”

European Perspective on Multiple Myeloma Treatment Strategies: Update Following Recent Congresses

“…In addition, the administration of bortezomib before and after ASCT in the HOVON/GMMG-HD4 trial (PAD induction, bortezomib maintenance) resulted in a significantly better outcome for patients with del17p than treatment in the control arm (VAD induction, thalidomide maintenance), suggesting that long-term administration of bortezomib may be beneficial for these patients [52]. The RVD combination is a preferred approach by some investigators [30, 100,105]. For patients with del17p, an upfront alloSCT may be an option if the patient has a donor and is in a good general condition [106].…”

Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Retrospective Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

“…However, studies indicate RIC alloSCT could be of interest in these presumably high-risk subgroups [36,37]. The induction regimens for MM have dramatically changed over the last years, and the combination of new immunomodulators such as proteasome inhibitors and IMiDs could offer to MM patients very high rates of response, including a large proportion of CRs [38,39]. The integration of these novel therapies with the immunotherapeutic platform of allotransplant offers considerable promises in the treatment of MM in the near future but still needs to be evaluated [39,40].…”

“…The induction regimens for MM have dramatically changed over the last years, and the combination of new immunomodulators such as proteasome inhibitors and IMiDs could offer to MM patients very high rates of response, including a large proportion of CRs [38,39]. The integration of these novel therapies with the immunotherapeutic platform of allotransplant offers considerable promises in the treatment of MM in the near future but still needs to be evaluated [39,40]. In our study, bortezomib treatment before alloSCT worsened NRM in a univariate analysis but did not affect survival outcomes in a multivariate analysis; the use of other new agents, such as IMiDs, were not evaluated in this study because of the small representation in the data available.…”