Challenge accepted: Breaking boundaries in therapy

Multiple myeloma is rare, but is one of the most common tumors of bone and bone marrow. Annually, there are about six to eight new cases per 100,000 inhabitants. Almost all patients develop from an asymptomatic premalignant stage. Treatment is divided into initial therapy of asymptomatic or symptomatic myeloma and treatment of relapsed disease.

Research into multiple myeloma (MM) is steadily gaining in importance. It accounts for approximately 1% of all cancers and approximately 10% of hematologic malignancies. The median age of onset is 72 years, which is why it is also declared an age-related disease. The causes have not yet been detected. However, some risk factors have been identified that may increase the risk of cancer (Table 1) . The course of MM is highly variable and the clinical behavior remarkably heterogeneous. Excess production of a monoclonal protein can cause kidney problems, amyloidosis, or peripheral neuropathy. If the bone marrow is infiltrated, fatigue, bone pain, susceptibility to infection and bleeding may be added.

Initial play it safe

The treatment should be adapted individually to the particular need. In recent years, major advances have been made in the therapeutic management of MM. Nevertheless, a cure is not (yet) possible for the majority of those affected. Younger and fit patients usually receive autologous stem cell transplantation after initial diagnosis. All other affected individuals are most commonly treated with a three-drug combination of the proteasome inhibitor bortezomib, the immunomodulator lenalidomide, and the corticosteroid dexamethasone. This can achieve a very good and rapid reduction of tumor mass without affecting stem cell mobilization.

Maintain good status

Despite intensive and well effective therapy concepts, the majority of affected individuals experience a recurrence. Therefore, the benefit of maintenance therapy has been discussed for a long time. For example, bortezomide is available for this purpose, for which a prolongation of progression-free survival has been shown in comparison to thalidomide, as well as for overall survival. High-risk patients in particular seem to benefit from this. Lenalidomide and ixazomib can also be used for maintenance therapy.

Focus on recurrence therapy

While good progress has been made in first-line treatment, mainly through synergistic combinations, the possibilities in later lines are currently still stagnating. The median progression-free survival in relapsed/refractory MM is 3-4 months. To initiate appropriate recurrence therapy, factors considered include age, performance status, comorbidities, type, efficacy, and tolerability of prior treatment, number of prior lines of treatment, available remaining treatment options, interval since last therapy, and type of recurrence. Combinations of the new agents (e.g., bortezomib, lenalidomide, pomalidomide, carfilzomib, ixazomib, thalidomide) with dexamethasone or cytostatics may be selected. Combinations are preferable to monotherapies because they achieve a faster and better quality therapeutic response and usually also result in longer disease control.