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. 2022 Apr 18:13:20406207221082043.
doi: 10.1177/20406207221082043. eCollection 2022.

The impact of bortezomib-based induction in newly diagnosed multiple myeloma with chromosome 1q21 gain

Hoi Ki Karen Tang  1 , Chi Yeung Fung  1 , Gareth J Morgan  2 , Shaji Kumar  3 , Lisa Siu  4 , Ho Wan Alvin Ip  5 , Sze Fai Yip  6 , Ka Ngai Harry Lau  7 , Chi Kuen Lau  8 , Harold Lee  9 , Kwan Hung Leung  10 , Bonnie Kho  11 , Howard Wong  11 , Cheong Ngai  1 , Yu Yan Hwang  1 , Joycelyn Sim  1 , Yok Lam Kwong  1 , Chor Sang Chim  12
Affiliations

The impact of bortezomib-based induction in newly diagnosed multiple myeloma with chromosome 1q21 gain

Hoi Ki Karen Tang et al. Ther Adv Hematol. .

Abstract

Introduction: Bortezomib has been reported to favourably impact the outcomes of t(4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown.

Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t(14;16), t(4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells.

Results: +1q identified in 167 (66.8%) and associated with t(4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t(4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069).

Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.

Keywords: chromosomal aberrations; fluorescence in situ hybridization; gain 1q; multiple myeloma; risk stratification.

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Conflict of interest statement

Conflict of interest statement: The authors declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
OS and EFS among MM patients with +1q (red) and without +1q (blue).
Figure 2.
Figure 2.
Post-relapse/progression survival among +1q (red) and without +1q (blue).
Figure 3.
Figure 3.
OS and EFS comparing without +1q (blue), amp 1q (green), and gain 1q (red).
Figure 4.
Figure 4.
OS according to +1q and ASCT status (without +1q and ASCT: blue, +1q and ASCT: red, and +1q and no ASCT: green).
Figure 5.
Figure 5.
OS according to risk score 0 (blue), 1–2 (red) and 3–4 (green).
See this image and copyright information in PMC

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