High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma

MMRF CoMMpass Network

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R2=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.

Original languageEnglish (US)
Pages (from-to)e612
JournalBlood Cancer Journal
Volume7
Issue number9
DOIs
StatePublished - Sep 22 2017

Fingerprint

Multiple Myeloma
Disease-Free Survival
Mutation
Missense Mutation
Standard of Care
Survival Analysis
Chromosome Aberrations
Neoplasms
Survival
Therapeutics
Population

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma. / MMRF CoMMpass Network.

In: Blood Cancer Journal, Vol. 7, No. 9, 22.09.2017, p. e612.

Research output: Contribution to journalArticle

@article{5b4d7f54bc0b464f9932a62508c27d97,
title = "High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma",
abstract = "Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R2=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.",
author = "{MMRF CoMMpass Network} and A. Miller and Y. Asmann and L. Cattaneo and E. Braggio and J. Keats and D. Auclair and S. Lonial and Russell, {S. J.} and Stewart, {A. K.}",
year = "2017",
month = "9",
day = "22",
doi = "10.1038/bcj.2017.94",
language = "English (US)",
volume = "7",
pages = "e612",
journal = "Blood Cancer Journal",
issn = "2044-5385",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - High somatic mutation and neoantigen burden are correlated with decreased progression-free survival in multiple myeloma

AU - MMRF CoMMpass Network

AU - Miller, A.

AU - Asmann, Y.

AU - Cattaneo, L.

AU - Braggio, E.

AU - Keats, J.

AU - Auclair, D.

AU - Lonial, S.

AU - Russell, S. J.

AU - Stewart, A. K.

PY - 2017/9/22

Y1 - 2017/9/22

N2 - Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R2=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.

AB - Tumor-specific mutations can result in immunogenic neoantigens, both of which have been correlated with responsiveness to immune checkpoint inhibitors in highly mutagenic cancers. However, early results of single-agent checkpoint inhibitors in multiple myeloma (MM) have been underwhelming. Therefore, we sought to understand the relationship between mutation and neoantigen landscape of MM patients and responsiveness to therapies. Somatic mutation burden, neoantigen load, and response to therapy were determined using interim data from the MMRF CoMMpass study (NCT01454297) on 664 MM patients. In this population, the mean somatic and missense mutation loads were 405.84(s=608.55) and 63.90(s=95.88) mutations per patient, respectively. There was a positive linear relationship between mutation and neoantigen burdens (R2=0.862). The average predicted neoantigen load was 23.52(s=52.14) neoantigens with an average of 9.40(s=26.97) expressed neoantigens. Survival analysis revealed significantly shorter progression-free survival (PFS) in patients with greater than average somatic missense mutation load (N=163, 0.493 vs 0.726 2-year PFS, P=0.0023) and predicted expressed neoantigen load (N=214, 0.555 vs 0.729 2-year PFS, P=0.0028). This pattern is maintained when stratified by disease stage and cytogenetic abnormalities. Therefore, high mutation and neoantigen load are clinically relevant risk factors that negatively impact survival of MM patients under current standards of care.

UR - http://www.scopus.com/inward/record.url?scp=85041467364&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041467364&partnerID=8YFLogxK

U2 - 10.1038/bcj.2017.94

DO - 10.1038/bcj.2017.94

M3 - Article

C2 - 28937974

AN - SCOPUS:85041467364

VL - 7

SP - e612

JO - Blood Cancer Journal

JF - Blood Cancer Journal

SN - 2044-5385

IS - 9

ER -