**1. Introduction**

Multiple myeloma (MM) is a hematooncological disease, and in recent years, overall survival of patients has been significantly increased. Improvement of treatment results is connected not only to the introduction of autologous transplantation of hematopoietic cells into the treatment strategy for younger patients in the 90s but also to the introduction of new beneficial drugs into clinics; in the first decade of this century, bortezomib, thalidomide and lenalidomide were introduced in [1]. These new drugs have repeatedly proven their high treatment efficacy in clinics in all age groups of patients, in primotherapy as well as refractory disease. There are also newer drugs currently under investigation, such as new proteasome inhibitors (carfilzo‐ mib, MLN9708 and other peroral proteasome inhibitors) and other immunomodulatory drugs (pomalidomide) with the aim to improve or maintain treatment effects and decrease unfav‐ orable effects in [2]. Using drugs from both these groups together with glucocorticoids and alkylating cytostatics had a major impact on prolonging survival of our patients as previously published. On the other hand, it is clear that use of only one of the new efficient drugs in combination with glucocorticoids and alkylating cytostatics does not lead to a cure in [3-7]. Optimization of dosage in combination with other drugs and the length of treatment have been clarified for thalidomide and bortezomib. Current dosage levels are different from recorded dosages in registration studies which in certain cases led to common or higher level of side effects than is acceptable; these side effects are reduced after optimization. Side effects, especially the long-term ones, may fundamentally influence the quality of life of patients after successful treatment. Nowadays, optimization of thalidomide and bortezomib treatments is almost completed and lenalidomide optimization is currently being processed in [5]. It is logical to think that optimization of efficient drugs is a never ending process that waits for each new efficient drug, for example carfilzomib and pomalidomide in the near future. A

© 2013 Hajek; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

variety of new drugs are being tested in clinical studies at phases I/II. In MM treatment, modern target therapies are being tested, such as monoclonal antibodies, kinase inhibitors or inhibitors of other target molecules connected to one of the signaling pathways important for malignant cells. Although treatment results of this group of drugs failed to reach expectations, we feel that they will produce very promising results in the future. Current treatment strategies will lead to a cure – a topic which is being discussed very seriously. In this chapter, the current state of affairs as well as the potentials of pharmacotherapy in MM will be discussed.

**b.** There is a variety of subtypes of multiple myeloma as this disease is very heterogenous. Thus, MM patients have various prognoses. All currently available classifications (based on ISS, cytogenetics, gene expression profiling, etc.) allow for classification of patients into groups with high, low or sometimes also intermediate risk for long-term survival. Unfortunately, no classification is specific enough to allow for prediction of treatment

Strategies for the Treatment of Multiple Myeloma in 2013: Moving Toward the Cure

http://dx.doi.org/10.5772/55366

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**c.** Based on the subclonal theory as well as new proofs, it seems probable that there are more clones of plasmocytes present at the time of diagnosis in one patient. Various subclones exist in a dynamic equilibrium, competing for limited resources with alternating domi‐ nance of various subclones at different time points. These clones have various character‐ istics including treatment sensitivity, and their ratio is significantly influenced by the treatment given to patients. It seems that new subclones may originate even during treatment and/or course of the disease in [12,13]. This finding has completely changed our view of efficacy of simple combination treatments with one novel agent. On the other hand, it is in complete harmony with important successes in the treatment including the cure in patients treated with intensive sequences of treatment protocols consisting of most efficient drugs. Drug combinations are essential to overcome resistance and the impact of

**d.** Treatment resistance to a specific drug does not have to be absolute. From the above mentioned subclonal theory, it is obvious that disease resistance to a certain drug in first progression does not have to be resistant to the same drug in the fourth progression. Then, the subclone sensitive to the drug may or may not be prevalent over resistant subclones. In case there are no other treatment options available, it is suitable to test sensitivity to

When deciding on a treatment, it is necessary to plan a complex treatment – not only anticancer treatment but also supportive treatment; it is important to think about relapse at the time of initial treatment, which drugs to use so that initial treatment does not block further steps in the future. Autologous transplantation is a basic part of treatment wherever possible. Today, treatment strategies use optimal choices of treatment lines, in an individual that should cover

Current treatment strategies for newly diagnosed patients are always aiming to reach deepest complete remission - molecular or immunophenotypic in [15,16]. In the first decade of this century, therapeutic regimens with one novel agent as backbone together with glucocorticoids and alkylating cytostatics were used as high standard based on randomized trials (Tab. 1).

success and prognosis for each individual patient in [9-11].

intra-clonal heterogeneity in [14].

**3. Treatment strategy and treatment line**

**4. Newly diagnosed multiple myeloma**

5-7 disease activities within 10 years of treatment if necessary.

previously used drugs.

## **2. Basic scientific data influencing current treatment strategies**

Our current treatment strategies originate from a variety of research data that may be shortly described as follows:

**a.** Every MM is preceded by a precancerosis called monoclonal gammopathy of undeter‐ mined significance (MGUS) in [8]. Individual stages starting from the occurrence of first clonal plasmocyte to MGUS, MM, refractory MM up to plasmocellular leukemia are concurrent; in one individual, they may be described as disease progression changing in time. Many internal and external factors influence the phase when the initial plasmocyte will develop into hematological malignancy requiring therapy (Fig.1).

MGUS, monoclonal gammopathy of undetermined significance

**Figure 1.** Natural history of multiple myeloma

