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KOS 2007: Individualizing Treatment in the Area of Multiple Novel Agents
By Jesús San Miguel, MD
Jesús San Miguel, MD
Hospital Clinico Universitario
Universidad de Salamanca
Salamanca, Spain
06.29.07

Hospital Clinico Universitario
Universidad de Salamanca
Salamanca, Spain

Note: The IMF did not receive permission to publish either the slides or the audio from this presentation, so we bring you a summary written by our medical writer, Lynne Lederman, PhD.

Like lymphoma, myeloma is probably not a single entity. Dr. San Miguel doesn’t believe that low risk disease exists, and prefers categorizing it as standard or high risk. He approaches treatment by first stratifying patients by age and whether or not they are transplant candidates. He also believes there is a role for maintenance therapy. He proposes bortezomib Adriamycin dexamethasone or lenalidomide dexamethasone for induction and MEL200 for transplant candidates with standard risk, followed by thalidomide or lenalidomide with or without prednisone or dexamethasone for maintenance (studies are needed). For early relapse (within a year) non-cross resistant agents followed by reduced intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) may be considered. Relapse within one to three years (intermediate) post-SCT can be treated sequentially with novel agents, with RIC allogeneic SCT in patients less than 55 years of age. For later relapse, he recommends re-induction and a second autologous SCT (ASCT).

For high risk transplant candidates, induction with alternative non-cross-reactive therapies and ASCT or RIC allogeneic SCT OR alternating targeted therapies with standard therapy (induction with a novel agent plus ASCT) is recommended; or these patients can be enrolled in clinical trials. For patients with primary refractory disease, myeloablative therapy supported by ASCT can be an option. For non-responding disease, patients with stable disease do as well as those with chemotherapy sensitive myeloma. However, progressive disease is associated with poor outcome and non-cross-reactive therapy with RIC allogeneic SCT is recommended. In the presence of renal insufficiency, VAD requires no dose adjustment, and bortezomib is effective.

For elderly patients who are not transplant candidates, six cycles of a melphalan-prednisone combination (MP with thalidomide, lenalidomide, or bortezomib, respectively) are good options. Dr. San Miguel suggested MP-V for patients with a risk of thromboembolic events or with poor adherence to oral therapy, MP-R for patients with antecedent peripheral neuropathy, MP with either oral IMiD for those far from a hospital, and MP-T as the lowest cost regiment of these combinations. He believes that lenalidomide with low dose dexamethasone may also be an option for elderly patients, even the very elderly (those over 75 years of age), although reducing the dose of the IMiDs or bortezomib may be appropriate. There are no data for maintenance therapy in the elderly. For newly diagnosed elderly patients in relapse, the condition of the patient must be considered in deciding between active therapy, clinical trials, or less active therapy (e.g., oral cyclophosphamide plus low dose prednisone).


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