TY - JOUR
T1 - Implications of MYC rearrangements in newly diagnosed multiple myeloma
AU - Abdallah, Nadine
AU - Baughn, Linda B.
AU - Vincent Rajkumar, S.
AU - Kapoor, Prashant
AU - Gertz, Morie A.
AU - Dispenzieri, Angela
AU - Lacy, Martha Q.
AU - Hayman, Suzanne R.
AU - Buadi, Francis K.
AU - Dingli, David
AU - Go, Ronald S.
AU - Hwa, Yi L.
AU - Fonder, Amie
AU - Hobbs, Miriam
AU - Lin, Yi
AU - Leung, Nelson
AU - Kourelis, Taxiarchis
AU - Warsame, Rahma
AU - Siddiqui, Mustaqeem
AU - Lust, John
AU - Kyle, Robert A.
AU - Ketterling, Rhett
AU - Bergsagel, Leif
AU - Greipp, Patricia
AU - Kumar, Shaji K.
N1 - Funding Information:
A. Dispenzieri reports personal fees from Janssen, and grants from Celgene, Takeda, Pfizer, and grants from Alnylma outside the submitted work. D. Dingli reports other from Juno and Karyopharm; and personal fees from Alexion, Apellis, GSK, Janssen, Milleneum/Takeda, and Rigel outside the submitted work. Y. Lin reports other from Janssen, BMS/Celgene/JUNO, Novartis, Kite/Gilead, Bluebird Bio, Takeda, Sorrento, Legend, and other from Gamida Cells outside the submitted work. N. Leung reports other from Takeda and AbbVie outside the submitted work. S.K. Kumar reports grants from NIH during the conduct of the study; grants and other from Celgene, Takeda, Janssen, BMS, KITE, Merck, Abbvie, Medimmune, Novartis, Roche-Genentech, Amgen, Tenebio, Carsgen; other from Celgene, Takeda, Janssen, Abbvie, Genentech, Amgen; and personal fees from Oncopeptides, Genecentrix, Cellectar, Beigene outside the submitted work. No potential conflicts of interests were disclosed by the other authors.
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/12
Y1 - 2020/12
N2 - Purpose: Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma. Experimental Design: This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1). Results: A rearrangement involving MYC was found in 8% of patients and was associated with elevated b2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)based or PI þ IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P < 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P ¼ 0.007). Conclusions: MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.
AB - Purpose: Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma, but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in patients with newly diagnosed multiple myeloma. Experimental Design: This is a retrospective study including 1,342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, who had cytogenetic testing by FISH at diagnosis, including MYC testing using the break apart FISH probe (8q24.1). Results: A rearrangement involving MYC was found in 8% of patients and was associated with elevated b2-microglobulin, ≥50% bone marrow plasma cells, IgA multiple myeloma, and the cooccurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)based or PI þ IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared with patients without MYC rearrangement (5.3 vs. 8.0 years, P < 0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5; P ¼ 0.007). Conclusions: MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in patients with newly diagnosed multiple myeloma.
UR - http://www.scopus.com/inward/record.url?scp=85100987431&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100987431&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-2283
DO - 10.1158/1078-0432.CCR-20-2283
M3 - Article
C2 - 33008815
AN - SCOPUS:85100987431
SN - 1078-0432
VL - 26
SP - 6581
EP - 6588
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -