TY - JOUR
T1 - Clinical Outcomes and Evolution of Clonal Hematopoiesis in Patients with Newly Diagnosed Multiple Myeloma
AU - Mouhieddine, Tarek H.
AU - Nzerem, Chidimma
AU - Redd, Robert
AU - Dunford, Andrew
AU - Leventhal, Matthew
AU - Sklavenitis-Pistofidis, Romanos
AU - Tahri, Sabrin
AU - El-Khoury, Habib
AU - Steensma, David P.
AU - Ebert, Benjamin L.
AU - Soiffer, Robert J.
AU - Keats, Jonathan J.
AU - Mehr, Shaadi
AU - Auclair, Daniel
AU - Ghobrial, Irene M.
AU - Sperling, Adam S.
AU - Stewart, Chip
AU - Getz, Gad
N1 - Publisher Copyright:
© 2023 The Authors.
PY - 2023/12
Y1 - 2023/12
N2 - Clonal hematopoiesis (CH) at time of autologous stem cell transplant (ASCT) has been shown to be associated with decreased overall survival (OS) and progression-free survival (PFS) in patients withmultiplemyeloma not receiving immunomodulatory drugs (IMiD).However, the significance of CH in newly diagnosed patients, including transplant ineligible patients, and its effect on clonal evolution during multiple myeloma therapy in the era of novel agents, has not been well studied. Using our new algorithm to differentiate tumor and germline mutations from CH, we detected CH in approximately 10%of 986 patients with multiple myeloma fromtheClinical Outcomes inMMto Personal Assessment of Genetic Profile (CoMMpass) cohort (40/529 transplanted and 59/457 non-transplanted patients). CH was associated with increased age, risk of recurrent bacterial infections and cardiovascular disease. CH at time of multiple myeloma diagnosis was not associated with inferior OS or PFS regardless of undergoing ASCT, and all patients benefited from IMiD-based therapies, irrespective of the presence of CH. Serial sampling of 52 patients revealed the emergence of CH over a median of 3 years of treatment, increasing its prevalence to 25%, mostly with DNMT3A mutations.
AB - Clonal hematopoiesis (CH) at time of autologous stem cell transplant (ASCT) has been shown to be associated with decreased overall survival (OS) and progression-free survival (PFS) in patients withmultiplemyeloma not receiving immunomodulatory drugs (IMiD).However, the significance of CH in newly diagnosed patients, including transplant ineligible patients, and its effect on clonal evolution during multiple myeloma therapy in the era of novel agents, has not been well studied. Using our new algorithm to differentiate tumor and germline mutations from CH, we detected CH in approximately 10%of 986 patients with multiple myeloma fromtheClinical Outcomes inMMto Personal Assessment of Genetic Profile (CoMMpass) cohort (40/529 transplanted and 59/457 non-transplanted patients). CH was associated with increased age, risk of recurrent bacterial infections and cardiovascular disease. CH at time of multiple myeloma diagnosis was not associated with inferior OS or PFS regardless of undergoing ASCT, and all patients benefited from IMiD-based therapies, irrespective of the presence of CH. Serial sampling of 52 patients revealed the emergence of CH over a median of 3 years of treatment, increasing its prevalence to 25%, mostly with DNMT3A mutations.
UR - http://www.scopus.com/inward/record.url?scp=85195184602&partnerID=8YFLogxK
U2 - 10.1158/2767-9764.CRC-23-0093
DO - 10.1158/2767-9764.CRC-23-0093
M3 - Article
AN - SCOPUS:85195184602
SN - 2767-9764
VL - 3
SP - 2560
EP - 2571
JO - Cancer Research Communications
JF - Cancer Research Communications
IS - 12
ER -