Put a stop sign to aggressive multiple myeloma

Dr Francesca Gay - Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, Turin, Italy

My presentation is about aggressive disease and aggressive myeloma and it’s based on what are the definitions of aggressiveness in myeloma, which are several. There are some well-known prognostic features that mark the presence of an aggressive disease, such as the high risk cytogenetics, for example, such as the high ISS or the high LDH levels. But there are other features that we commonly don’t include in the baseline staging but that can have a prognostic impact such as, for example, the presence of extramedullary disease at disease presentation. Then there are other factors that we might consider in evaluating the aggressiveness of the disease and that are related to the response to treatment. So, the disease that is, for example, refractory to first-line therapy is an aggressive disease by definition, regardless of the baseline prognostic features that we can have. Another important factor is the duration of remission, for example after first-line, because patients relapsing early, meaning early relapse after a time of referred remission that is lower than expected with a specific therapy is, again, a marker of aggressive disease.

What is the current definition of aggressive disease?

I think there are several definitions because the myeloma field is really under development and there are many biological definitions. So, for example, thinking about the presence of FISH abnormalities, patients with deletion 17p are patients with a higher risk disease, in particular, if they have the mutation of p53. So I don’t think there is one single definition, there are several, and the field is really changing.

What kinds of treatments are currently available?

I think that there is no specific therapy for aggressive disease except that generally we use multi-agent chemotherapy using a combination of drugs with different mechanisms of action. There are several that can be used. Another important thing is to try to keep the pace in treating the disease, one cycle after the other without too long intervals, if they are not strictly necessary, to maintain the disease control, to increase the cytoreduction using autologous transplant and maybe double autologous transplant in patients who are eligible as an example.

What is the potential role of precision medicine?

I think that we still need to work on that, because there are very, very few data that can allow us to use a specific drug in a specific subset of disease like, for example, the use of venetoclax in patients who are translocation (11;14) positive. This is a drug still experimental; this is generally used in later lines of therapy, so this is an example of what can be precision medicine in myeloma; there are others. I think the biology of the disease is so complex that there is, of course, a role for precision medicine but we still have to work on it.

Are there other promising areas you hope to see develop in the future to help treat this disease?

I think that one is the strategy, the best strategy. We need to work on the best strategy according to prognostic features but according to response, implementing the MRD evaluation in clinical trials, to use it prospectively, to see if we can base our treatment decision and our treatment intensity also on the response and in particular on the MRD.