Hematologic Oncology Update, Issue 1, 2016 (Video Program)Monitoring and management of smoldering myeloma
4:17 minutes.
TRANSCRIPTION:
DR FONSECA: Probably the most important thing with smoldering right now is the definition of what is truly smoldering. In the olden days, being conservative about therapy it was almost a badge of honor for myeloma doctors, because we didn’t want to treat too early. But the question that has been reformulated recently is, are you ever treating too late? So there have been expanded criteria by the International Myeloma Working Group looking at patients who would have a very significant risk of progression within the next 2 years. Those 3 new factors are excessive plasmacytosis over 60%, more than 1 focal lesion in an MRI or excessive skewing, over 100 in your free light chain. Those would be factors that would make us think about need of starting therapy. I think outside of a clinical trial, most patients with smoldering should not be treated. But I think most patients with smoldering should be carefully worked up. And that includes imaging studies and the bone marrow and the genetic testing and all of that, because the risk of progression is so much higher. It’s been documented for smoldering multiple myeloma, 10% per year for the first 5 years, so that’s 50% at 5 years, 3% per year for the next 5 years, so that’s another 15%, so cumulative at 10 years, the risk of progression is 65%. And I think if you’re 60 and you have smoldering multiple myeloma and have a risk of 65% of having progressed to myeloma by the age of 70, we would sure hope that doesn’t happen, because you present again with renal failure. You present again with a fracture or, perhaps even worse, you get vertebral compression fractures that are going to give you lifelong pain. And that is really where the finesse comes for the clinical judgment in managing these patients. DR LOVE: When you do treat, how do you approach choice of treatment? DR FONSECA: My philosophy has been, I never treat smoldering. If I treat, it’s as if I’m treating myeloma. So if there is a person who has now crossed the boundary where I’m concerned about this, then we just start full therapy as if they were myeloma. And there’s 2 important points here that I would like to make for our community colleagues. When you look at the traditional CRAB criteria, there are some criteria that are benign and some that are dangerous. In fact, I just had a publication that I call “The Claws of the CRAB.” So the claws of the crab are bone disease and renal failure, because anemia and hypercalcemia, they can be corrected. They can be fixed. But if you have a patient who develops with renal failure, you can’t always correct that. And when you have someone who has fractures, you can’t always fully correct that, and you have patients who may have lifelong symptoms. So those are the ones you have to be paying attention to. For renal failure, this largely depends on the serum concentration of the free light chain. If the free light chain is under 100 or 150 mg per deciliter or, as is tested in some labs, 1,000 to 1,500 mg per liter, the risk of renal disease is low. So if the patient has low levels, then it’s a little bit easier to follow that patient with regard to the renal toxicity, but it’s important to focus on the bone disease and the impending fractures. And we don’t have, as of yet, very good biomarkers to determine who’s at great risk for bone disease. DR LOVE: So you said in those situations where you’re going to treat somebody with smoldering, you treat them as myeloma. And I don’t know if I pinned you down enough earlier in the interview to figure out what your current up-front therapy is. What is it? DR FONSECA: So based on our mSMART guidelines, we’re choosing VRd right now as standard therapy for most patients. We do propose that for high-risk patients. One could consider carfilzomib/lenalidomide and dexamethasone. And this is for the transplant eligible. I do think there still are quite a few patients that could be treated with the CyBorD regimen. For the nontransplant eligible, we still make the distinction between the low-risk and the high-risk ones, with the low-risk ones being great candidates for lenalidomide and dexamethasone and high risk, for the most part, combinations of len/bortezomib and dexamethasone. |