Early detection of relapse in multiple myeloma patients with high risk genetics using quantitative immunoprecipitation-mass spectrometry (QIP-MS) in blood: an enhanced surveillance platform for the Myeloma XV, RADAR trial.

Background: Multiple Myeloma (MM) is an incurable blood cancer and survival from diagnosis can range from a few months to over 10 years. Patients with genetic high risk (HR) disease are more likely to relapse early and median overall survival in this group is less than 3 years. Predicting which patients will relapse early is challenging and patients require new methods of monitoring their cancer so that relapse can be detected at the earliest possible stage when they are less likely to have developed symptoms such as bone disease, kidney failure and anaemia and more likely to respond to salvage treatment. Aims: As early relapse is a common feature of HR disease we will focus on this group of patients, taking part in the NCRi Myeloma XV RADAR trial to test whether a new monitoring technique called quantitative immunoprecipitation-mass spectrometry (QIP-MS) can improve our ability to predict and identify early relapse. The research questions for this project are: i) can QIP-MS detect low level residual disease in HR MM patients, defining those at high risk of early relapse and ii) can 3 monthly monitoring using QIP-MS detect relapse at least 3 months earlier in 50% of patients who relapse within 24 months of diagnosis according to standard criteria. Standard monitoring for the detection of relapse in RADAR includes monthly serum protein electrophoresis (SPEP), serum immunofixation (IFE) and serum free light chain (sFLC) testing in blood plus bone marrow aspirations at baseline, 3 months and 9 months post autologous stem cell transplant (ASCT). QIP-MS is 30 times more sensitive than the next most sensitive bloods test (sFLC) to detect monoclonal proteins which are a sign of active MM. Methods: We will add 3 monthly QIP-MS testing at baseline, 3,6,9,15,18, 21 months post ASCT to enable detection of low level residual cancer after the transplant and predict relapse sooner than waiting for other less sensitive blood tests to become positive. How the results of this research will be used: Patients with HR MM require better ways to predict and detect early relapse to improve their survival. They also wish to have fewer bone marrows which are inconvenient and painful. We will show that QIP-MS positivity predicts which patients in complete response by standard tests (SPEP/IFE/sFLC) will relapse early, and show that rising QIP-MS positivity reflects resurgent disease which is a feature of early progression and warrants early change of treatment.