Background: Chromosome 1q21 copy number gain (1q21+) has been identified as an independent adverse prognostic factor in newly diagnosed multiple myeloma (NDMM). However, current international and domestic guidelines do not recommend solitary 1q21+ (gain or amplification) as a sole criterion for defining high-risk (HR) disease. This study aimed to evaluate the prognostic value of chromosome 1q21 gain/ amplification (1q21+) and other cytogenetic abnormalities in Chinese patients with NDMM.

Methods: We retrospectively analyzed NDMM patients treated between July 2013 and June 2022. Patients were stratified based on interphase FISH results into groups: no 1q21+, isolated 1q21+, 1q21+ with non-high-risk cytogenetic abnormalities (NHRCA), and 1q21+ with high-risk cytogenetic abnormalities (HRCA).

Positivity cut-offs were defined as follows: ≥20% of cells for deletions and ≥10% of cells for translocations involving chromosome 14. Treatment response was assessed per IMWG criteria. Progression-free survival (PFS) was defined as the time from treatment initiation to disease progression, death, or end of follow-up, whichever occurred first. Overall survival (OS) was defined as the time from treatment initiation to death or end of follow-up, whichever occurred first.

Results: A total of 658 patients were included (388 male; median age 63 years, range 31-88). 301 patients had 1q21+ (isolated: n=106; with NHRCA: n=92; with HRCA: n=103). With a follow-up cutoff of June 30, 2025 (median follow-up 47.9 months), the median progression-free survival (PFS) for the entire cohort was 37.2 months. Median PFS was 49.5 months for no 1q21+, 33.7 months for isolated 1q21+, 38.0 months for 1q21+ with NHRCA, and 18.2 months for 1q21+ with HRCA. Patients without 1q21+ had significantly superior PFS compared to all other groups combined (P<0.001), except when compared to the 1q21+ with NHRCA group (P=0.423); patients with 1q21+ and HRCA had significantly worse PFS than all other groups (P<0.001). The median overall survival (OS) for the entire cohort was 75.7 months. Median OS was 100.8 months for no 1q21+, 69.9 months for isolated 1q21+, 78.8 months for 1q21+ with NHRCA, and 39.8 months for 1q21+ with HRCA. Patients without 1q21+ had significantly superior OS compared to all other groups combined (P<0.01), except when compared to the 1q21+ with NHRCA group (P=0.427); patients with 1q21+ and HRCA had significantly worse OS than all other groups (P<0.01).

Conclusion: 1q21 gain is a significant adverse prognostic factor in Chinese NDMM patients. Isolated 1q21+ significantly shortens PFS, while co-existence with HRCA drastically worsens survival outcomes (median OS <40 months). The impact of concomitant NHRCA on survival in patients with 1q21+ remains unclear and warrants further investigation. We recommend incorporating 1q21+ into risk stratification systems.

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2025
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