Multiple myeloma: Therapy and new treatments #ASH09

There have been significant scientific advances in the field of blood cancers, and leading experts continue to gain a better understanding of how certain diseases progress in order to discover new treatment options and provide patients with the best care. Research presented today at the 51st Annual Meeting of the American Society of Hematology explores optimal induction therapies for managing multiple myeloma, the importance of advance care planning for improved quality of life, and a potential new first-line therapy for patients with non-Hodgkin lymphoma.

"Studies such as these are designed to improve the quality of evaluation, diagnosis, and treatment of various blood cancers,” said moderator of the press conference Richard A. Van Etten, MD, PhD, Director of Tufts Medical Center Cancer Center in Boston. “The results of these studies not only give hematologists a better understanding of disease progression, but also direct them to the measures that are safer and more effective in treating their patients."

Multiple myeloma is a type of blood cancer that affects white blood cells known as plasma cells and is common among the elderly. In the United States, the incidence of this disease is increasing at an alarming rate with 13,000-15,000 new cases diagnosed each year. Over the last few years the treatment of elderly patients older than 65 years with multiple myeloma has changed, mainly due to the introduction of novel agents such as thalidomide, bortezomib, and lenalidomide. According to results from the Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone (VISTA) trial, the combination of bortezomib, melphalan, and prednisone is significantly superior to melphalan and prednisone alone, which has been the current standard of care for multiple myeloma patients who cannot receive a stem cell transplant. However, research has not yet confirmed whether an alkylating agent (chemical compound) or an immunomodulatory therapy (drug that suppresses or stimulates the body’s immune response) is the optimal partner for bortezomib. Researchers from the Spanish Myeloma Group designed a study to better determine if melphalan or thalidomide should be used as part of induction therapy (the initial treatment given to patients) in combination with bortezomib. The study showed that elderly patients were able to receive less aggressive treatment regimens of induction therapy by supplementing them with a maintenance treatment.

In order to evaluate whether the induction therapy regimen could be further optimized by decreasing toxicity while maintaining efficacy, the intensity of both treatment regimens was reduced as compared with the VISTA regimen, but supplemented with maintenance therapy. In this study, 260 patients with a median age of 75 years were randomized to receive a modified induction schedule of six cycles of bortezomib, melphalan, and prednisone (VMP) or bortezomib, thalidomide, and prednisone (VTP) as induction therapy followed by maintenance therapy with bortezomib and thalidomide (VT) or bortezomib and prednisone (VP) for up to three years.

Study results indicate that modified induction schedules for both VMP and VTP were highly effective with similar overall response rates (80 percent for VMP and 81 percent for VTP), which were determined using the European Group for Blood and Marrow Transplantation (EBMT) criteria, and complete remission rates (20 percent for VMP and 27 percent for VTP), but there was a clear difference in the toxicity profile of each group. In the VMP regimen there was a higher incidence of neutropenia (abnormally low count of white blood cells) and infections, but VTP resulted in the development of cardiac toxicity. The frequency of grade 3-4 peripheral neuropathy (PN) was 5 percent in the VMP group. Maintenance therapy with either VT or VP also markedly improved the quality of patient responses with a good safety profile, increasing complete response from 23 percent up to 42 percent, with no significant differences in response rates between the VT and VP treatment arms. In addition, both maintenance regimens resulted in an acceptable toxicity profile.

"Melphalan with prednisone has been the gold standard for the treatment of elderly multiple myeloma patients for the past 40 years, but novel combination therapies have emerged as superior options,” said lead author Maria-Victoria Mateos, MD, PhD, Attending Physician, Hematology Department at the Hospital Universitario de Salamanca in Spain. “In this study, we demonstrate that the combination of a reduced dosage for induction therapy followed by maintenance therapy may be a novel approach for treating this patient population."