Upfront Therapeutic Options in Multiple Myeloma

Keith Stewart, MB, ChB:The first case we’re going to discuss today is a 61-year-old female who presents with multiple myeloma, the t(4;6) translocation. This would indicate that there are some high-risk features, based on the genetics of her disease. She’s treated with a combination of lenalidomide, bortezomib, and dexamethasone and attains a partial remission. Subsequently, she goes on to autologous stem cell transplant and lenalidomide maintenance given her high-risk features.

About 18 months’ post transplantation, this relatively young woman comes back with evidence of biochemical progression, a rising monoclonal protein despite therapy with lenalidomide. At this stage, the patient remains relatively asymptomatic with a biochemical relapse only and no change in her blood count.

This young woman received lenalidomide, bortezomib, and dexamethasone therapy as her initial treatment. This has become, essentially, the gold standard of care in the United States. Recent phase III trials have shown that this combination is superior to the use of lenalidomide and dexamethasone alone, at least with respect to progression-free survival and response rate.

This patient obtained a partial remission and went on to receive an autologous stem cell transplant. Recent studies, particularly from France, have continued to demonstrate the value of transplant even in the era of new drugs, such as the ones that this patient received. Specifically, their trial, which was in over 600 patients, demonstrated much better prolonged progression-free survival, in patients who received a transplant compared with those patients who just maintained the same therapy over about a 9-month period.

Case Scenario 1:

July 2011

• The patient is a 61-year-old Caucasian female who was diagnosed with stage II MM. Genetic testing showed her to have t(4:16). At the time she was treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy followed by autologous stem cell transplantation.
• She achieved a partial response with RVD and remained in remission. Based on her high-risk cytogenetics, the patient was placed on lenalidomide maintenance therapy.

August 2016

• Routine follow up shows that her M-protein levels have now risen to 1.4 g/dL and her light chain levels continue to rise.
• Although she has developed mild anemia and her creatinine level is slightly elevated to 1.3 mg/dL, she continues to work full-time, has no bone pain, and a has a normal calcium level.