Analysis of Clinical Characteristics and High-Risk Factors of Patients with Extramedullary Relapse Multiple Myeloma

Background: Extramedullary relapse of multiple myeloma (MM) is often resistant to existing treatments, and has an extremely poor prognosis, but our understanding of extramedullary relapse is still limited. This study intends to deepen our understanding of this type of disease and find high-risk factors for extramedullary relapse through a retrospective analysis.

Methods: This study retrospectively analyzed the clinical data of 471 newly diagnosed MM (NDMM) patients treated in our center from May 2013 to June 2020. The incidence of extramedullary involvement, clinical characteristics, impact on the prognosis of patients at relapse, as well as the risk factors for extramedullary relapse in NDMM patients were analyzed.

Results: Among the 471 NDMM patients, a total of 267 patients had disease relapse or progression during follow-up, including 64 (24.0%) patients with extramedullary relapse, among which 22 (8.2%) patients with extramedullary-bone related (EMB) relapse and 42 (15.7%) patients with extramedullary extraosseous (EME) relapse. Survival analysis suggested that compared with patients with relapse but without extramedullary involvement, patients with extramedullary relapse had significantly worse overall survival (OS) (30.8 months vs. 53.6 months, P=0.012), and further multivariate analysis confirmed that extramedullary relapse (HR=1.95, P=0.002) was independent prognostic predictors affecting OS in relapsed patients. Compared with patients without extramedullary relapse during follow-up, patients with extramedullary relapse were more common in IgD subtypes, elevated lactate dehydrogenase (LDH) levels at diagnosis, diagnosis with extramedullary involvement, enlarged spleen at diagnosis and patients did not achieve partial remission (PR) or above after treatment. Multivariate analysis confirmed that elevated LDH (OR=2.44, P=0.005), hypercalcemia (OR=1.83, P=0.044), extramedullary involvement (OR=4.07, P<0.001) and enlarged spleen (OR=2.46, P=0.004) at the time of MM diagnosis were independent risk factors for extramedullary relapse in NDMM patients. The 3-year of extramedullary relapse rates for NDMM patients with 0-1, 2-3 or 4 factors was 20%, 45.1% and 100%, respectively.

Conclusion: This study suggested that among patients treated with bortezomib-based regimens, the extramedullary relapse rate was about 24%, with EME relapse being more common, suggesting extremely poor survival. Elevated LDH, hypercalcemia, extramedullary involvement and enlarged spleen at the time of MM diagnosis were independent risk factor for extramedullary relapse in NDMM patients.

No relevant conflicts of interest to declare.