The Importance of FISH Signal Cut-off Value and Copy Number Variation for 1q21 in Newly Diagnosed Multiple Myeloma: Is it Underestimated?

Background: The cut-off value for gain/amplification of 1q21(1q21+) was 20% according to the recommendations of the European Myeloma Network and there were limited studies concerning less than 20%. Meanwhile, the copy number variation of 1q21+ remains controversial. Our purpose was to evaluate the significance of clone size and copy numbers of 1q21+ in Chinese newly diagnosed multiple myeloma (NDMM).

Patients and methods: We retrospectively analyzed 161 consecutive NDMM patients who were tested for common cytogenetic abnormalities at diagnosis by fluorescence in-situ hybridization and 5% was set for the threshold for 1q21+ by a comparative study.

Results: Ninety-six (59.6%) patients were determined for 1q21+ by fluorescence in-situ hybridization including 38 had ≥4 copies. In clone size analyses, the 2-year progression-free survival (PFS) in <5% group was superior in comparison with 5% to 20% (65.2% vs. 47.0%, P = .041) and >20% group (65.2% vs. 37.5%, P < .001), whereas there was no significant difference between the 2 latter groups. Patients with ≥ 4 copies of 1q21 had inferior 2-year PFS compared to patients with 3 copies (23.3% vs. 50.6%, P = .028) and 2 copies (23.3% vs. 65.2%, P < .001). Bortezomib-based treatment might benefit the PFS for patients with 3 copies but could not improve the adverse effect of ≥ 4 copies. 1q21+ was an independent risk factor for inferior PFS and OS in multivariate analysis (P < .001 and P = .028).

Conclusion: Our results demonstrated that 5% was a reliable cut-off value for 1q21+, and 1q21+ was an adverse prognostic factor in NDMM, especially when ≥ 4 copies were present.