Doublets, Triplets, and More: Emerging Therapies for Multiple Myeloma

By Peter W. Marks, MD, PhD

Multiple myeloma treatment has advanced rapidly over the past several years. The introduction of new active agents has, in short order, transformed the management of affected individuals. Among these new myeloma drugs are the immune modulators thalidomide and lenalidomide and the proteasome inhibitor bortezomib. But we do not yet know the best methods for combining these agents with older therapies, such as melphalan and corticosteroids.

At yesterday’s Plenary Session, Dr. Maria-Victoria Mateos from the Hospital Universitario de Salamanca in Spain presented results on behalf of the Spanish Myeloma Group from a prospective, randomized trial in older patients with newly diagnosed multiple myeloma.  This study compared induction treatment with bortezomib, melphalan, and prednisone (VMP) to bortezomib, thalidomide (100 mg/day), and prednisone (VTP). This was followed by maintenance treatment with either bortezomib and thalidomide (VT) or bortezomib and prednisone (VP).

A total of 260 patients were enrolled. Individuals who completed six cycles of induction were then randomized to maintenance with VT or VP for up to three years. The doses and schedules employed for maintenance included bortezomib 1.3 mg/m2 administered on days 1, 4, 8, and 11 every three months, in combination with either continuous thalidomide 50 mg daily (VT) or prednisone 50 mg every other day (VP).

One of the notable findings was that the group treated with VMP induction followed by VT maintenance had statistically significant better progression-free survival than those treated with VTP followed by VP. Similar responses were noted in standard and high-risk groups, indicating that both of these therapeutic regimens can overcome traditional indicators of poor prognosis.

With respect to adverse events, VMP induction therapy was associated with a higher incidence of neutropenia and a higher incidence of infections than VTP. In contrast, VTP therapy was associated with a higher incidence of peripheral neuropathy than VMP as well as a higher incidence of serious cardiac events, although the absolute number of such events was small.

Dr. Mateos noted that perhaps the most important finding was that the poor prognosis of high-risk elderly patients could be overcome with either treatment regimen. This is good news on the myeloma front, and there is certain to be more news as the meeting progresses.

Dr. Marks indicated no relevant conflicts of interest.

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