EHA 2017: The Nature of Long Remissions

"I still haven't found what I'm looking for." U2

What makes one patient's remission longer than another? Dr.Bruno Paiva of the University of Navarra  quoted U2 and said that even though we are getting closer to learning more on this topic. he is not satisfied that we have enough information today to make definitive statements on the subject. He noted that some of the problem is not just the genetics of the myeloma cell, but the immune system of each individual patient. As an example, MGUS patients have a higher risk of infection than the regular population and smoldering myeloma patients with weak immunity progress to active myeloma at a faster rate. This may be why lenalidomide and dexamethasone helps high risk smoldering myeloma patients - the combo promotes T cells and natural killer cells which fight infection. This is interesting because normally dex suppresses the immune system. So shouldn't it be avoided? Dr. Paiva showed results from the QUIREDEX trial showing that it actually had no detrimental effects to the immune system when combined with the immunomodulators (like lenalidomide). He also mentioned that higher doses of proteasome inhibitors might depress the immune system but lower doses might actually boost it. We just don't know yet. Myeloma causes patients to have an impaired immune system because one antibody grows out of control, crowding out the other antibodies. Long term survival is associated with a unique immune profile. This is partly why the excitement of getting a complete response (CR) to a treatment should be balanced with the results of minimal residual disease testing.  According to Dr. Paiva, having a complete response to treatment is no better than a partial response unless you are minimal disease negative. MRD testing is also helpful if you want to understand how long a patient might go before relapsing (progression free survival). Because MRD testing is important to better understand why patients relapse, the new International Myeloma Working Group 2016 criteria now has four categories:

• Sustained MRD status (how long patients can stay MRD negative)
• Imaging for MRD (do new lesions show up on MRIs or PET-CT scans?)
• Flow cytometry MRD testing (tests taken from bone marrow)
• Sequencing MRD tests (DNA-based MRD tests)

The question for patients is: If I am MRD negative, can I stop treatment? To answer this, further study is needed to combine 1) patient factors 2) myeloma tumor genetics 3) MRD monitoring 4) immune system profiling and 5) big data sets for answers.