IV. Initial treatment of multiple myeloma

The initial treatment of myeloma is rapidly evolving as newer and newer regimens are tested in phase II and III trials [1,2]. Over 20 modern regimens have been reported to be highly effective in a variety of recent trials [3]. Separating ‘promising’ results that should be interpreted as merely hypothesis that need further testing from those that provide clear evidence of clinical benefit requiring a change in practice is challenging. Part of this conundrum is driven by different standards used by experts to adjudicate what constitutes ‘evidence’. Part of this is driven by regulatory pressures and cost. A large part of the variance in interpretation of data and ensuing recommendations is however dictated by competing philosophies on the approach to the treatment of myeloma. In evaluating the available data and to make recommendations for initial therapy of the disease, certain key tenets can be used as universal guiding principles. First, although rational ideas such as the potential benefits of eradicating all myeloma cells are intuitive and attractive, it is prudent to wait for empiric evidence of clinical benefit. Numerous apparently rational strategies in medicine have been shown eventually to produce no benefit, or even harm to patients. Second, it is important to have a clear definition of clinical benefit. In myeloma, clinical benefit is not based on changes in surrogate markers, but rather on proof of prolongation or life or improvement in quality of life. Third, proof requires convincing data from randomized trials, not small uncontrolled studies. Finally, when there is no clear winner on the basis of the above three criteria, the default position should be to choose the least toxic, least expensive option. Although there are empiric data showing clear survival benefit from randomized trials with a few modern regimens such as melphalan, prednisone, thalidomide (MPT) and bortezomib, melphalan, prednisone (VMP), these come from trials in which these regimens were compared with old historical ones such as melphalan, prednisone (MP). Similar results from randomized trials