Baseline mutational patterns and sustained MRD negativity in patients with high-risk smoldering myeloma Journal Article

   

Authors:	Mailankody, S.; Kazandjian, D.; Korde, N.; Roschewski, M.; Manasanch, E.; Bhutani, M.; Tageja, N.; Kwok, M.; Zhang, Y.; Zingone, A.; Lamy, L.; Costello, R.; Morrison, C.; Hultcrantz, M.; Christofferson, A.; Washington, M.; Boateng, M.; Steinberg, S. M.; Stetler-Stevenson, M.; Figg, W. D.; Papaemmanuil, E.; Wilson, W. H.; Keats, J. J.; Landgren, O.
Article Title:	Baseline mutational patterns and sustained MRD negativity in patients with high-risk smoldering myeloma
Abstract:	Early results of a prospective phase 2 clinical trial of carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance in high-risk smoldering myeloma showed promising results that were previously published. Here, we provide novel insights into the genetic landscape of high-risk smoldering myeloma and information on sustained minimal residual disease (MRD) negativity with an expanded cohort of patients. Eighteen patients with high-risk smoldering myeloma were enrolled between 29 May 2012, and 14 January 2014. We included patients with newly diagnosed multiple myeloma enrolled in a parallel trial who received the same therapy (reference group). The overall response rate was 100%. With median potential follow-up of 43.3 months, 10 (63%) remain in MRD negativity, and the estimated 4-year progression-free and overall survival rates are 71% and 100%, respectively. Importantly, we report differences in mutational patterns in patients with high-risk smoldering myeloma and newly diagnosed multiple myeloma, reflected in a lower frequency of mutations in significant myeloma genes (6.6% vs 45%) and NFKB pathway genes (6.6% vs 25%). Treatment with carfilzomib, lenalidomide, and dexamethasone followed by lenalidomide maintenance was associated with a 100% response rate and 63% MRD negativity with a safety profile consistent with previous reports for this regimen. This study had a small numbers of participants, but there seemed to be important differences in the genetic landscape of patients with high-risk smoldering myeloma and those with newly diagnosed multiple myeloma, suggestive of a more treatment-responsive biology in early disease.
Keywords:	bortezomib; progression; heterogeneity; criteria; lenalidomide plus dexamethasone; monoclonal; gammopathy; precedes multiple-myeloma
Journal Title:	Blood Advances
Volume:	1
Issue:	22
ISSN:	2473-9529
Publisher:	American Society of Hematology
Date Published:	2017-10-10
Start Page:	1911
End Page:	1918
Language:	English
ACCESSION:	WOS:000412736200005
DOI:	10.1182/bloodadvances.2017005934
PROVIDER:	wos
PMCID:	PMC5728141
PUBMED:	29296837
Notes:	Article -- Source: Wos

https://synapse.mskcc.org/synapse/works/has_related_data_chk/116703