**9. Inhibitors of proteasomes**

**6. Drugs available for intensive treatments**

6 Multiple Myeloma - A Quick Reflection on the Fast Progress

neuropathy and quality of life considerations).

**8. Immunomodulatory drugs (IMiDs)**

subgroup of patients in [28].

in [29,28,30].

It is necessary to note that novel agents, imunomodulatory drugs (thalidomide, lenalidomide, pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib), are key players currently used in therapeutical protocols and/or in the clinical trials. The 'old' drugs, such as alkylating cytostatics and glucocorticoids, still belong to the most effective group of drugs in multiple myeloma. These old drugs are used in most treatment protocols. The therapeutic strategy in newly diagnosed patients is described in details in another chapter (Induction Therapy in Multiple Myeloma). The same drugs could be used in a relapse setting depending on the components of initial therapy, efficacy and toxicity of the initial therapy, patient status and circumstances of relapse (age, performance status, glucose metabolism, aggressive vs nonaggressive relapse, bone marrow reserve, renal function impairment, pre-existing peripheral

**7. Drugs available for the maintenance part of treatment regimen**

Decade after decade, there is a change in opinion about benefits of maintenance therapy. While conventional cytostatics and glucocorticoids were used because of lack of any other option, the era of interferon alpha ended with the introduction of immunomodulatory drugs. It is also true that worldwide, interferon alpha had never been accepted as routine maintenance therapy because of its comparatively high toxicity as well as minimal benefit for the unclassified

Meta-analysis of randomized clinical studies of phase III with thalidomide as maintenance therapy confirms the benefits of use after autologous transplantation. Statistically significant increase of PFS in six studies and overall survival prolongation in three studies were noted. On the other hand, only one third of patients tolerated thalidomide maintenance therapy for more than a year. At this point, when there are less toxic drugs available for maintenance therapy, thalidomide is recommended as a part of short-term intensive consolidation therapies

Lenalidomide was tested in two independent randomized clinical trials of phase III as maintenance treatment after autologous transplantation. Both these trials, CALGB 100104 and IFM 2005-02, demonstrated benefit from lenalidomide compared to placebo, which showed a major decrease in risk of progression by 60% in [21] and an improvement of three-year PFS in the group with lenalidomide (61% vs. 34%) in [20]. Based on new analyses (follow-up of 28 months), there was a statistically significant improvement in overall survival in Len/Dex treated groups of patients in comparison to the placebo treated group of patients, regardless of short follow-ups in [21]. Its role in maintenance therapy is highlighted by improved results In the study GEM/Pethema, patients were induced by VMP (bortezomib, melphalan, predni‐ solon) or VTP (bortezomib, thalidomid, prednisolon) and randomized for maintenance treatment (VT or VP) for 3 years. Maintenance treatment with bortezomib increased IF-CR from 24% to 42% in [32]. Maintenance treatment with bortezomib was better after autologous transplantation in comparison to thalidomide (PFS 28 vs. 35 months; p=0.002), and overall survival benefit was seen not only for the whole group (p = 0.049) but also for high risk patients in [33]. So far, there is not enough information about maintenance therapy with bortezomib although the data are promising. The change in the route of bortezomib administration from intravenous to subcutaneous significantly reduced toxicity, mainly peripheral polyneurop‐ athy in [34]. Thus, long-term use of bortezomib will be more suitable for patients starting at the end of the year 2012. Moreover, novel proteasome inhibitors that undergo clinical trials have limited toxicity and per oral route of administration that further increased their potential for maintenance therapy in [35].
