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Early Relapse Risk in Patients with Newly Diagnosed Multiple Myeloma Characterized by Next-generation Sequencing.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Sep 15; Vol. 26 (18), pp. 4832-4841. Date of Electronic Publication: 2020 Jul 02. - Publication Year :
- 2020
-
Abstract
- Purpose: Duration of first remission is important for the survival of patients with multiple myeloma.<br />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).<br />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.<br />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.<br /> (©2020 American Association for Cancer Research.)
- Subjects :
- Aged
Antineoplastic Combined Chemotherapy Protocols pharmacology
Disease Progression
Disease-Free Survival
Drug Resistance, Neoplasm genetics
Female
Follow-Up Studies
High-Throughput Nucleotide Sequencing
Humans
Immunologic Factors pharmacology
Immunologic Factors therapeutic use
Longitudinal Studies
Male
Middle Aged
Multiple Myeloma genetics
Multiple Myeloma mortality
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local prevention & control
Prospective Studies
Proteasome Inhibitors pharmacology
Proteasome Inhibitors therapeutic use
Risk Assessment methods
Time Factors
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Multiple Myeloma drug therapy
Neoplasm Recurrence, Local epidemiology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 26
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 32616499
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-20-0951