Case Study 1: A Diagnosis of Stage II Multiple Myeloma
Insights From: Rafael Fonseca, MD, Mayo Clinic; Gareth Morgan, MD, PhD, UAMS Myeloma Institute; Thomas G. Martin, MD, UCSF Helen Diller Family Comprehensive Cancer Center
Gareth Morgan, MD, PhD: A 56-year-old male presented to the clinic with the features of multiple myeloma with bone disease, anemia, and a slightly low platelet count. His kidney function was fine. Following staging, he came out as being high ISS-II, and the treatment regimen that was chosen was Revlimid (lenalidomide), Velcade (bortezomib), and dexamethasone. He had a good response to this, and after 5 cycles he underwent stem-cell harvest. It was a good harvest. And then, he subsequently underwent a 200 mg/m2 melphalan autologous stem-cell transplant, which he tolerated well, and went into a complete clinical remission, which was maintained for some years.
Rafael Fonseca, MD: The patient presented to us in this case is really receiving optimal therapy, and I think the majority of centers now have moved to a triplet-based induction regimen, particularly with a combination of bortezomib, lenalidomide, and dexamethasone. There could be a variation in this particular case that I think will be relevant, and that is that this person has a translocation between chromosomes 14 and 16. The t(14;16) remains one of the most challenging subtypes of myeloma for treatment. While I see some patients who have done very well with t(14;16), there are many cases that are quite challenging. According to some of the guidelines, including the ones we have at the Mayo Clinic, a patient like this could be considered for induction therapy based on carfilzomib, so something like carfilzomib, lenalidomide, and dexamethasone. However, I think anyone would agree this is a standard induction regimen. I think it’s optimally positioned to produce that first response in a patient anticipating a subsequent stem-cell transplant.
Gareth Morgan, MD, PhD: A patient with t(14;16), which is a subset of myeloma that has more high-risk cases within it, would undoubtedly have led to me using Revlimid maintenance. It would likely have been beneficial because there’s evidence saying it’s active in high-risk and low-risk disease. Personally, I probably would have added a combination of maintenance, either with Velcade or—if we were certain he had high-risk disease—with daratumumab. In combination, that would potentially have been useful.
All of the data that have come out recently for all of the agents—for IMiD drugs, for proteasome inhibitors including carfilzomib, and for monoclonal antibodies—suggest that there’s a therapeutic benefit from longer term exposure. So, it’s no longer de rigueur to just give 6 cycles and stop. It’s important to get people to stay on treatment well out beyond a year, and sometimes out beyond 2 to 3 years. That gives you the best, most durable responses, and the best long-term outcomes.
Thomas G. Martin, MD: In this case, we have a young patient who has high-risk multiple myeloma. They received standard induction therapy and an autologous stem-cell transplant. In fact, at that point in time, it would be common and standard of care for us to put them on maintenance-based therapy.
There is some controversy in terms of high-risk disease. What is the best therapy? There was a recent randomized trial from the United Kingdom that certainly showed a benefit with lenalidomide-based maintenance therapy, but there are other trials that suggest chromosome inhibitors might be a better choice in patients who have high-risk disease. My personal practice is that I usually combine therapy. I combine therapy with either lenalidomide, bortezomib, and dexamethasone as consolidation posttransplant in maintenance at a little lower dose; or carfilzomib, lenalidomide, and dexamethasone as consolidation therapy or maintenance posttherapy. I think that is the most effective strategy for patients who have high-risk disease, like the patient in this case.