Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing. Clinical cancer research : an official journal of the American Association for Cancer Research

Mattia D'Agostino, Gian Maria Zaccaria, Bachisio Ziccheddu, Even H. Rustad, Elisa Genuardi, Andrea Capra, Stefania Oliva, Daniel Auclair, Jennifer Yesil, Paola Colucci, Jonathan J. Keats, Manuela Gambella, Sara Bringhen, Alessandra Larocca, Mario Boccadoro, Niccolò Bolli, Francesco Maura, Francesca Gay

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Duration of first remission is important for the survival of patients with multiple myeloma. EXPERIMENTAL DESIGN: 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). RESULTS: 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%, P < 0.001) and more frequently acquired double refractoriness to immunomodulatory drugs (IMiD) and proteasome inhibitors (PI; 21% vs. 8%, P < 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; P < 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 TP53 mutation (OR, 3.78, P < 0.001), high lactate dehydrogenase levels (OR, 3.15, P = 0.006), λ-chain translocation (OR, 2.25, P = 0.033), and IGLL5 mutation (OR, 2.15, P = 0.007). Carfilzomib-based induction (OR, 0.15, P = 0.014), autologous stem-cell transplantation (OR, 0.27, P < 0.001), and continuous therapy with PIs and IMiDs (OR, 0.34, P = 0.024) mitigated the risk of early PD. CONCLUSIONS: 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.
Original languageEnglish
Pages (from-to)4832-4841
Number of pages10
JournalClinical Cancer Research
Volume26
Issue number18
DOIs
Publication statusPublished - 2020

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