Early relapse risk in patients with newly diagnosed multiple myeloma characterized by next-generation sequencing Journal Article

  

Authors:	D'Agostino, M.; Zaccaria, G. M.; Ziccheddu, B.; Rustad, E. H.; Genuardi, E.; Capra, A.; Oliva, S.; Auclair, D.; Yesil, J.; Colucci, P.; Keats, J. J.; Gambella, M.; Bringhen, S.; Larocca, A.; Boccadoro, M.; Bolli, N.; Maura, F.; Gay, F.
Article Title:	Early relapse risk in patients with newly diagnosed multiple myeloma characterized by next-generation sequencing
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 (32.8months). 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), lambda-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.
Keywords:	classification; death; disease; continuous therapy
Journal Title:	Clinical Cancer Research
Volume:	26
Issue:	18
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2020-09-15
Start Page:	4832
End Page:	4841
Language:	English
ACCESSION:	WOS:000572826000015
DOI:	10.1158/1078-0432.Ccr-20-0951
PROVIDER:	wos
PUBMED:	32616499
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/172373