Clinical treatment of newly diagnosed multiple myeloma

Abstract

The introduction of the novel agents, thalidomide, bortezomib and lenalidomide as part of the frontline induction both in transplant and non-transplant candidates have markedly improved the anti-myeloma efficacy of the different therapeutic regimens and improved patients’ prognosis. Current treatment goals are aimed to further improve the rate of complete remission, time to progression, progression-free survival and overall survival without increasing toxicity. Besides, different strategies are being developed in the elderly population as this group of patients requires a closer monitoring with individualized, dose-modified regimens to improve tolerability while maintaining their quality of life. This article reviews the current landscape of frontline treatment both in transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma.

Keywords:

• frontline therapy
• multiple myeloma
• newly diagnosed

Financial & competing interests disclosure

This study was supported by the “Instituto de Salud Carlos III” (PI 09/01882 and PI 12/01569 to J.dl. R.). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• For transplant candidates, induction treatment is aimed to increase the rate of complete response. Triplet regimens including a proteasome inhibitor and an immunomodulatory drugs (lenalidomide-bortezomib-dexamethasone, bortezomib-thalidomide-dexamethasone) should be considered as the standard of care for this group of patients.

• Autologous stem cell transplantation is still the most useful post-induction treatment for younger patients. Other consolidation strategies have shown promising results, although the optimum type and duration of consolidation treatment have not been defined.

• Post-transplant maintenance has shown significant impact on event-free survival but without uniform data regarding the impact of this strategy on overall survival (OS). As with consolidation, no definitive data about which could be the best maintenance strategy are available.

• For non-transplant-eligible patients, the goal of therapy should be to achieve and maintain the maximal response while limiting treatment-related toxicity. A careful geriatric assessment is mandatory before choosing the best induction regimen and the most appropriate drugs dosage for this heterogeneous group of patients.

• Bortezomib with MP and continuous lenalidomide and low-dose dexamethasone-based therapy have shown similar results in terms of progression-free survival and OS and both should be considered alternative frontline induction regimens for elderly patients. Lenalidomide and low-dose dexamethasone for a fixed number of cycles (18) and Thalidomide in combination with MP are also comparable in terms of progression-free survival.

• In non-transplant candidates, maintenance treatment with novel agents is emerging as a new strategy to sustain disease control and delay progression. However, longer follow-up is needed to assess which is the best strategy which could be the optimal duration, and the final benefit on OS.

• As with younger patients, future development of second- and third-generation immunomodulatory drugs and proteasome inhibitor, and new drug families such as mAbs and histone deacetylase inhibitors will also enable us to further improve outcomes in this population of patients.