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

Hoi Ki Karen Tang, Chi Yeung Fung, Gareth J. Morgan, Shaji Kumar, Lisa Siu, Ho Wan Alvin Ip, Sze Fai Yip, Ka Ngai Harry Lau, Chi Kuen Lau, Harold Lee, Kwan Hung Leung, Bonnie Kho, Howard Wong, Cheong Ngai, Yu Yan Hwang, Joycelyn Sim, Yok Lam Kwong, Chor Sang Chim

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
JournalTherapeutic Advances in Hematology
StatePublished - Mar 2022


  • chromosomal aberrations
  • fluorescence in situ hybridization
  • gain 1q
  • multiple myeloma
  • risk stratification

ASJC Scopus subject areas

  • Hematology


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