Implications and outcomes of MRD-negative multiple myeloma patients with immunofixation positivity.

person Marcella Tschautscher Mayo Clinic, Rochester, MN info_outline Marcella Tschautscher, Dragan Jevremovic, Francis Buadi, Martha Lacy, Morie A. Gertz, Angela Dispenzieri, Prashant Kapoor, David Dingli, Suzanne R. Hayman, John Anthony Lust, Stephen J. Russell, Nelson Leung, Yi Lin, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma M. Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar, Ronald S. Go

Authors person Marcella Tschautscher Mayo Clinic, Rochester, MN info_outline Marcella Tschautscher, Dragan Jevremovic, Francis Buadi, Martha Lacy, Morie A. Gertz, Angela Dispenzieri, Prashant Kapoor, David Dingli, Suzanne R. Hayman, John Anthony Lust, Stephen J. Russell, Nelson Leung, Yi Lin, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma M. Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar, Ronald S. Go Organizations Mayo Clinic, Rochester, MN, Division of Hematopathology, Mayo Clinic, Rochester, MN, Division of Hematology, Mayo Clinic, Rochester, MN, Vyriad and Mayo Clinic, Rochester, MN Abstract Disclosures Research Funding Other Background: Minimal residual disease (MRD) assessment in multiple myeloma (MM) has improved our ability to assess disease activity, resulting in more advanced prognostication. While MRD assessment remains confined to the bone marrow (BM) plasma cell population, serum studies including immunofixation (IFE) are required to complete response evaluation. The significance of those who are MRD neg yet have detectable monoclonal protein through IFE remains unclear. Methods: We retrospectively studied 256 MM patients who had MRD assessment via the Euroflow multiparametric flow cytometry on the BM with concomitant serum IFE testing. Patients who were MRD neg were included in the study. Outcomes included probability of disease progression (PD) at 1 year. The Cox-proportional hazards model was used to compare probability of PD among different groups. Time to progression (TTP) was calculated as the difference from date of MFC analysis to PD in months. Results: Among the entire cohort, 178 (70%) patients were MRD neg and median follow-up from MRD assessment was 6.3 months. Among these patients, 74 (42%) had a positive IFE at the time of MRD analysis. Within the MRD neg /IFE pos group, 31 (42%) patients remained IFE pos after a median follow up of 5.5 mo from initial MRD/IFE testing while 34 patients eventually became IFE neg after a median of 2.8 mo with no subsequent IFE available in 9 patients. The 1 year probability of PD in the MRD neg /IFE neg group was 20% compared to 41% in the MRD neg /IFE pos group (P < 0.01, Wilcoxon test). When comparing subsequent IFE status in those who were MRD neg /IFE pos , those who remained IFE pos had a trend towards shorter TTP compared to patients who later became IFE neg . Conclusions: Persistent monoclonal protein in the face of MRD negativity predicts for a shorter TTP. This likely reflects persistent disease that was not sampled on the BM aspirate in many of these patients compared to those who eventually become IFE neg with a trend towards longer TTP owing to the prolonged half-life and therefore clearance of M protein. This supports the current strategy of assessing for MRD at the time of suspected complete response to reduce the chance of positive MRD tests and thus avoidance of multiple BM exams.