Minimal Residual Disease Negativity Does Not Overcome Poor Prognosis in High-Risk Multiple Myeloma: A Single-Center Retrospective Study

• Published in: Clinical lymphoma, myeloma and leukemia myeloma and leukemia, 2020-05, Vol.20 (5), p.e221-e238
• Main Authors: Kunacheewa, Chutima, Lee, Hans C., Patel, Krina, Thomas, Sheeba, Amini, Behrang, Srour, Samer, Bashir, Qaiser, Nieto, Yago, Qazilbash, Muzzaffar H., Weber, Donna M., Feng, Lei, Orlowski, Robert Z., Lin, Pei, Manasanch, Elisabet E.
• Format: Article
• Language: English
• Subjects: Genetic risk; High-risk myeloma; Minimal residual disease; Newly diagnosed myeloma; Prognosis
• ISSN: 2152-2650; 2152-2669
• DOI: 10.1016/j.clml.2020.01.001

Minimal residual disease (MRD) is a standard measurement for response assessment in multiple myeloma (MM). Despite new treatments, high-risk MM patients continue to have poor prognosis. We evaluated the effect of MRD negativity in high-risk versus standard-risk patients. We retrospectively evaluated all consecutive MM patients who underwent routine MRD testing by 1-tube 8-color advanced flow cytometry with 2,000,000 events and sensitivity level 10−5 at our center from 2015 to 2018 after initial therapy. Kaplan-Meier and log-rank test were used to assess survival estimates and differences between study groups. One hundred thirty-six patients with MRD testing after initial therapy or autologous stem-cell transplantation were identified. At a median follow-up of 14 months (range, 1-36 months), progression-free survival and overall survival were significantly worse in high-risk versus standard-risk patients. During the study period, 50% of high-risk group had experienced disease progression (relapse and/or death) versus 20% in the standard-risk group (P = .0006). No patients with standard-risk died, but 4 (14%) in the high-risk group did (P = .0007). Regardless of MRD status, high-risk patients had statistically significant worse progression-free survival than standard-risk patients. At median follow-up, those with disease 10% standard-risk/MRD negative; 20% standard-risk/MRD positive; 40% high-risk/MRD negative; and 45% high-risk/MRD positive had either experienced relapse or died (P = .0041). MRD status did not significantly affect overall survival in either group (P = .0914); however, longer follow-up is needed to assess survival. Genetic abnormalities remain a powerful prognostic indicator for MM, regardless of MRD status. For newly diagnosed MM patients treated with novel triple-drug initial therapy and frontline autologous stem-cell transplantation, MRD-negative status did not mitigate the poor-prognosis outcomes of high-risk MM patients. Patients with multiple myeloma (MM) who experience deep remissions, including minimal residual disease (MRD) negativity, have better clinical outcomes compared to those do not. We aimed to describe the effect of testing for MRD negativity in a cohort of MM patients outside of a clinical trial. For most patients, MRD negativity supports improved clinical outcomes. However, in our cohort of patients with high-risk MM, MRD negativity does not seem to affect the overall poor prognosis.