Clinical Outcome of Extramedullary Multiple Myeloma in the Era of Novel Agents: Insights From a Multicenter Study

ABSTRACT This study aimed to discuss the clinical outcomes of extramedullary multiple myeloma in the era of novel agents, based on the largest dataset regarding extramedullary multiple myeloma in China. This study included 597 patients without extramedullary disease (EMD) (non‐EMD), 324 with extramedullary bone‐related disease (EMB) and 138 with de novo extramedullary extraosseous disease (EME). There were no significant differences in overall survival (OS, p = 0.638) or progression‐free survival (PFS, p = 0.195) between non‐EMD and EMB patients. However, de novo EME patients exhibited significantly worse OS ( p < 0.01) and PFS ( p < 0.01) compared to both EMB and non‐EMD groups. Among non‐EMD and EMB patients, those with ≥ 2 high‐risk cytogenetic abnormalities (HRA) experienced extremely poor prognoses, categorizing them as ultra‐high‐risk multiple myeloma. Similarly, de novo EME patients with ≥ 1 HRA demonstrated very poor outcomes and should also be considered ultra‐high risk. Notably, single transplantation was shown to mitigate the adverse prognosis of de novo EME patients. Furthermore, the daratumumab bortezomib lenalidomide dexamethasone (DVRD) quadruplet regimen showed potential as effective frontline therapies for de novo EME patients, offering hope for improved treatment outcomes in this challenging subgroup. These findings suggest that de novo EME represents an extremely poor prognosis and should be treated as a distinct entity within the multiple myeloma population. Furthermore, the results indicate that EMB may need to be excluded from the current EMD definition to better delineate these subgroups and guide therapeutic strategies.