Does high risk cytogenetics as a sole abnormality influence your treatment decision for smoldering multiple myeloma?

Several studies have looked at the prognostic factor of FISH abnormalities and risk of progression of SMM to active disease (Neben et al., 2013; Rajkumar et al., 2013). Deletion 17p and t(4;14) are associated with the highest risk of progression, with median time to progression of 24 months, as reported by the Mayo group (Rajkumar et al., 2013). This time to progression is similar to the high risk group defined by the 20/2/20 model, where the rate of progression at two years was 47.4% (Lakshman et al., 2018). Interestingly, hyperdiploidy, which is considered favorable in newly-diagnosed multiple myeloma, has a higher risk of progression than a normal FISH pattern (Neben et al., 2013; Rajkumar et al., 2013).  

In the ECOG study, the numbers of patients with known high risk FISH (defined as t(4;14) or deletion 17p) were too small, N = 7, to draw any conclusions. In general, our practice for patients with SMM and high risk FISH is to recommend a clinical trial or to observe very closely (e.g. q3 months). This is the subset of patients I would consider treating based on biochemical progression (e.g. rapidly rising monoclonal protein). Moreover, if the decision is to treat based on an evolving picture, I would treat as if they have symptomatic MM with a standard regimen (as opposed to single agent lenalidomide as done in the ECOG trial).

- Andrew Yee, MD and Noopur Raje, MD