Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing.

Abstract

Duration of first remission is important for the survival of patients with multiple myeloma. From the CoMMpass study (NCT01454297), 926 patients with newly diagnosed multiple myeloma, characterized by next-generation sequencing, were analyzed to evaluate those who experienced early progressive disease (PD; time to progression, TTP ≤18 months). After a median follow-up of 39 months, early PD was detected in 191/926 (20.6%) patients, 228/926 (24.6%) patients had late PD (TTP >18 months), while 507/926 (54.8%) did not have PD at the current follow-up. Compared with patients with late PD, patients with early PD had a lower at least very good partial response rate (47% vs. 82%, <i>P</i> < 0.001) and more frequently acquired double refractoriness to immunomodulatory drugs (IMiD) and proteasome inhibitors (PI; 21% vs. 8%, <i>P</i> < 0.001). Patients with early PD were at higher risk of death compared with patients with late PD and no PD (HR, 3.65; 95% CI, 2.7-4.93; <i>P</i> < 0.001), showing a dismal median overall survival (32.8 months). In a multivariate logistic regression model, independent factors increasing the early PD risk were <i>TP53</i> mutation (OR, 3.78, <i>P</i> < 0.001), high lactate dehydrogenase levels (OR, 3.15, <i>P</i> = 0.006), λ-chain translocation (OR, 2.25, <i>P</i> = 0.033), and <i>IGLL5</i> mutation (OR, 2.15, <i>P</i> = 0.007). Carfilzomib-based induction (OR, 0.15, <i>P</i> = 0.014), autologous stem-cell transplantation (OR, 0.27, <i>P</i> < 0.001), and continuous therapy with PIs and IMiDs (OR, 0.34, <i>P</i> = 0.024) mitigated the risk of early PD. Early PD identifies a high-risk multiple myeloma population. Further research is needed to better identify baseline features predicting early PD and the optimal treatment approaches for patients at risk.