European Perspective on Multiple Myeloma Treatment Strategies in 2014

Abstract

The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions,the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in asmallbut growing numberof patients.Inaddition, nowadaysit is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator forselectingtherapy. Inyounger, fit patients,a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option.Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and adecisionregardingpost-ASCTtherapyshould onlybemadeafter detailed discussion of the pros and cons with the individual patient. Two-and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. The Oncologist 2014;19:829-844 Implications for Practice: Ongoing advances in the management of multiple myeloma have resulted in substantial improvements in outcomes for patients. It is necessary to critically evaluate trial results to assess how new findings should be incorporated into treatment strategies. The manuscript aims to provide recommendations for routine clinical practice that can be broadly applied based on the discussions among European experts and a review of evidence from clinical studies.

Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores

“…21 Other studies have confirmed the relevance of assessing frailty, quality of life and physical activity. 18,32,34,35 The assessment of organ function, such as renal and lung impairment, has shown to influence survival rates, treatment toxicity and early death. 8,16,36 Moreover, tumor genetics have been reported to relevantly influence the clinical heterogeneity of MM.…”

A question of class: Treatment options for patients with relapsed and/or refractory multiple myeloma

“…With most patients receiving a backbone therapy of an IMiD and dexamethasone or a PI and dexamethasone, the development of disease that is refractory to one or both of these classes is a concern in RRMM. A key question following the development of refractory disease is whether to switch the class of agent from the previous line or to switch to another treatment option within the same class of agent (Ludwig et al, 2014).…”

Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter-based drug-drug interactions

“…Originally developed for the study of proteasome physiology, proteasome inhibitors soon demonstrated significant antineoplastic activity (2) that, starting with bortezomib, was successfully applied in the treatment of multiple myeloma (3). Subsequently, bortezomib has become an almost indispensable part of the gold standard therapy regimen, significantly improving the treatment outcomes of affected patients (4). However, its clinical applicability is considerably impeded by dose-limiting toxicity (5) and by primary or secondary drug-resistance (6,7).…”