Therapeutic Advancements in Multiple Myeloma - Episode 1

Smoldering Multiple Myeloma

Smoldering multiple myeloma is, as you all know, a precursor state for active multiple myeloma, and has recently been redefined. Myeloma now is treated even before the development of hypercalcemia, renal disease, anemia, or bone manifestations. If there's myeloma defining events, so even in the absence of an organ dysfunction, if you have more than 60% plasma cells, or your Kappa lambda ratio is more than 100-fold aberrant, or if you have bone lesions on sensitive imaging, you get treated. As a consequence, those patients who are leftover are now called smoldering myeloma.

And in particular, those patients who are at high risk for progressing from smoldering to active myeloma are those in whom we consider intervening. So what does that mean? Those patients who don't have active myeloma, as I just mentioned, but do have more than 20%, but less than 60% plasma cells, they have a Kappa lambda ratio of greater than 20-fold abnormal or they have more than 2 grams of monoclonal protein. If your patient has 2 or more of those features, they're at high risk to progress from smoldering to active myeloma. Now in Spain, lenalidomide (Revlimid) and dexamethasone and in America, single agent lenalidomide has been utilized in an attempt to delay the progression of smoldering to active myeloma. And in particular, Dr. Lonial and colleagues have recently studied lenalidomide 25 milligrams orally for 21 of 28 days continuously as a single agent to try to delay the progression of individuals with smoldering myeloma to active disease. And in the high-risk group that I just defined, we call it the to 2020 more than two grams of protein more than 20% plasma cells and Kappa lambda ratio, more than 20-fold abnormal, he demonstrated a significant benefit. So that's the subgroup of patients in particular, that can be considered for single agent lenalidomide therapy.

There are multiple clinical trials now ongoing to try to prevent the progression of patients with high-risk smoldering disease to active myeloma. And these include immune therapies such as vaccinations, or monoclonal antibodies, or myeloma therapies that we are using that are being tested for their value earlier. The final point I would make is the standard of care is still not to treat smoldering myeloma and follow those patients every 3 months, with myeloma, blood profiling, and with bone imaging as indicated. If your patient though, has the high-risk features that I've mentioned, you can consider lenalidomide now, or you can consider clinical trials of novel targeted and immune therapies. It's important to realize that when we intervene in patients with smoldering myeloma, these are patients who are asymptomatic. So we really need to think about interventions that don't have an adverse side effect profile. It stands to reason if we can intervene early someday and prevent patients from ever getting active myeloma, this will be an opportunity for curative therapy.