TY - JOUR
T1 - Cytogenetic abnormalities in multiple myeloma
T2 - association with disease characteristics and treatment response
AU - Abdallah, Nadine
AU - Rajkumar, S. Vincent
AU - Greipp, Patricia
AU - Kapoor, Prashant
AU - Gertz, Morie A.
AU - Dispenzieri, Angela
AU - Baughn, Linda B.
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 - Bergsagel, Leif
AU - Ketterling, Rhett
AU - Kumar, Shaji K.
N1 - Funding Information:
P.K. received research funding from Takeda Pharmaceuticals, Celgene, and Amgen. M.A.G. served as a consultant for Millennium Pharmaceuticals and received honoraria from Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Novartis, GlaxoSmithKline, Prothena, Ionis Pharmaceuticals, and Amgen. A.D. received research funding from Celgene, Millennium Pharmaceuticals, Pfizer, and Janssen and received a travel grant from Pfizer. M. Q.L. received research funding from Celgene. D.D serves as a consultant for Alexion, Apellis, Glaxo Smith Kline, Janssen, Millenium/Takeda, Rigel, and received research funding from Juno Therapeutics and Karyopharm Therapeutics. N.L. serves on an advisory board for Takeda Pharmaceuticals. S.K. K. served as a consultant for Celgene, Millennium Pharmaceuticals, Onyx Pharmaceuticals, Janssen, and Bristol-Myers Squibb and received research funding from Celgene, Millennium Pharmaceuticals, Novartis, Onyx Pharmaceuticals, AbbVie, Janssen, and Bristol-Myers Squibb. The remaining authors declare that they have no conflict of interest.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Cytogenetic abnormalities are found in most multiple myeloma (MM) patients. Although their prognostic value has been well studied, there are limited data on the association of primary cytogenetic abnormalities with disease characteristics and treatment response. This study was designed to evaluate these associations. This is a retrospective study including 2027 Mayo Clinic patients diagnosed with MM between February 2004 and February 2018 who had cytogenetic testing by FISH at diagnosis. Translocations t(4;14), t(14;16), t(6;14), and t(14;20) were associated with anemia, beta2microglobulin >5.5 µg/ml and ≥50% bone marrow plasma cells; t(4;14) was associated with higher serum monoclonal protein and plasma cell proliferation. Overall response rate to proteasome inhibitor (PI)-based treatment was higher for IgH translocations compared to trisomies (83% vs. 71%, P = 0.002), but was higher for trisomies with immunomodulatory drug (IMiD)-based treatment (87% vs. 75%, P < 0.001). Time to next treatment was longer with trisomies than IgH translocation with IMiD-based (32.1 vs. 18.4 months, P < 0.001) and PI + IMiD-based (44.0 vs. 27.4 months, P = 0.003) treatments. Outcomes were superior with PI + IMiD combinations in all groups. Our results show that t(4;14), t(14;16), t(6;14), and t(14;20) are associated with high-risk disease characteristics, and IgH translocations and trisomies may be associated with better responses to PIs and IMiDs, respectively.
AB - Cytogenetic abnormalities are found in most multiple myeloma (MM) patients. Although their prognostic value has been well studied, there are limited data on the association of primary cytogenetic abnormalities with disease characteristics and treatment response. This study was designed to evaluate these associations. This is a retrospective study including 2027 Mayo Clinic patients diagnosed with MM between February 2004 and February 2018 who had cytogenetic testing by FISH at diagnosis. Translocations t(4;14), t(14;16), t(6;14), and t(14;20) were associated with anemia, beta2microglobulin >5.5 µg/ml and ≥50% bone marrow plasma cells; t(4;14) was associated with higher serum monoclonal protein and plasma cell proliferation. Overall response rate to proteasome inhibitor (PI)-based treatment was higher for IgH translocations compared to trisomies (83% vs. 71%, P = 0.002), but was higher for trisomies with immunomodulatory drug (IMiD)-based treatment (87% vs. 75%, P < 0.001). Time to next treatment was longer with trisomies than IgH translocation with IMiD-based (32.1 vs. 18.4 months, P < 0.001) and PI + IMiD-based (44.0 vs. 27.4 months, P = 0.003) treatments. Outcomes were superior with PI + IMiD combinations in all groups. Our results show that t(4;14), t(14;16), t(6;14), and t(14;20) are associated with high-risk disease characteristics, and IgH translocations and trisomies may be associated with better responses to PIs and IMiDs, respectively.
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U2 - 10.1038/s41408-020-00348-5
DO - 10.1038/s41408-020-00348-5
M3 - Article
C2 - 32782240
AN - SCOPUS:85089280614
VL - 10
JO - Blood Cancer Journal
JF - Blood Cancer Journal
SN - 2044-5385
IS - 8
M1 - 82
ER -