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. 2020 Aug 11;10(8):82.
doi: 10.1038/s41408-020-00348-5.

Cytogenetic abnormalities in multiple myeloma: association with disease characteristics and treatment response

Nadine Abdallah  1 , S Vincent Rajkumar  1 , Patricia Greipp  2 , Prashant Kapoor  1 , Morie A Gertz  1 , Angela Dispenzieri  1 , Linda B Baughn  2 , Martha Q Lacy  1 , Suzanne R Hayman  1 , Francis K Buadi  1 , David Dingli  1 , Ronald S Go  1 , Yi L Hwa  1 , Amie Fonder  1 , Miriam Hobbs  1 , Yi Lin  1 , Nelson Leung  1   3 , Taxiarchis Kourelis  1 , Rahma Warsame  1 , Mustaqeem Siddiqui  1 , John Lust  1 , Robert A Kyle  1 , Leif Bergsagel  4 , Rhett Ketterling  2 , Shaji K Kumar  5
Affiliations

Cytogenetic abnormalities in multiple myeloma: association with disease characteristics and treatment response

Nadine Abdallah et al. Blood Cancer J. .

Abstract

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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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1. First line treatment.
Drugs and combinations used for first-line treatment in patients included in the study. IMiD immunomodulatory drug, PI proteasome inhibitor.
Fig. 2
Fig. 2. Treatment outcomes for IgH translocation and trisomies groups.
Comparison of a overall response rate, b ≥VGPR rate, and c time to next treatment with PI-based (blue), IMiD-based (red), PI + IMiD-based (green) and other (purple) first-line treatments for patients with IgH translocations (without trisomies), trisomies (without IgH translocations) and patients with both IgH translocations and trisomies. IgH immunoglobulin heavy chain, IMiD immunomodulatory drug, PI proteasome inhibitor, trans translocation, VGPR very good partial response.
Fig. 3
Fig. 3. TTNT by cytogenetic group.
Comparison of the time to next treatment (TTNT) between patients with high-risk IgH translocations (red curve), those with standard-risk IgH translocations (green curve), and those with trisomies without IgH translocation (blue curve) receiving a PI-based, b IMiD-based, c PI + IMiD-based treatment and d other treatments. IgH immunoglobulin heavy chain, IMiD immunomodulatory drug, PI proteasome inhibitor.
See this image and copyright information in PMC

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