IMiD Sequencing in Relapsed Myeloma with Keith Stewart, MB, ChB Case 1 - Episode 2

The Value of Maintenance Therapy in Multiple Myeloma

Keith Stewart, MB, ChB:A number of randomized trials have shown that maintenance therapy is of value, with respect to progression-free survival, for a majority of our patients. Specifically, a meta-analysis recently described that overall survival could also be improved if all of those studies were grouped together. Thus, in the United States at least, use of lenalidomide in a posttransplant setting has become quite common, although there remains some controversy due to cost and due to potential side effects.

In this case, this lady had high-risk myeloma, justifying even more the use of maintenance therapy, which, in this case, was lenalidomide alone, but in retrospect could have perhaps contained other agents. For example, the use of bortezomib is sometimes recommended for high-risk patients, often given subcutaneously every 2 weeks as first described by the Dutch in one of their large randomized trials. The long-term use of a proteasome inhibitor, particularly bortezomib in this case, has been demonstrated to overcome some of the high-risk features such as we saw in this young woman.

A patient like this is at relatively high risk for early relapse, so we would recommend follow-up at least every month, 2 months, or if she was very stable, every 3 months. But generally speaking, because of the risk of relapse, because the patient is still on therapy, I would probably see this patient myself every 2 months. This patient has developed a biochemical relapse, but is still working with good performance status and no signs of end organ damage. Traditionally, one would be safe following this patient for some period of time until there was some signs of impending problems. However, more recently, our approach has been to intervene earlier. This is because we have many new drugs available which are actually, if anything, more effective than the drugs this patient received as her initial therapy. So, my own bias is to treat early and not wait for problems to emerge.

There are multiple options for treatment for this woman who’s experienced a biochemical relapse, but with good performance status and normal renal function. The one drug we might want to change is lenalidomide, since she’s already progressing on that drug and escalating the dose is not often that effective. We have multiple new choices. Last year, there were four new drugs approved by the Federal Drug Administration in the United States. They include carfilzomib, a proteasome inhibitor; ixazomib, an oral proteasome inhibitor; elotuzumab, a monoclonal antibody; and recently, we have seen that the drug daratumumab is powerful and effective in these patients.

In this particular case, I think we should still be aggressive with her care. She has high-risk disease. She is progressing relatively quickly despite maintenance after autologous stem cell transplant. In this situation, I would personally turn to our most potent and most effective drugs, which is the proteasome inhibitor carfilzomib, which is the most rapidly acting and produces the deepest response. And I would escalate her immune modulatory therapy from lenalidomide to the drug pomalidomide.

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.