Frontiers in oncology · 2026
Chromosome 1q alterations in transplant-eligible multiple myeloma: clinical impact of copy number and co-occurring high-risk cytogenetic features.
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Strassl Irene, Bindeus Daniel, Burghofer Jonathan, Erdel Martin, Buxhofer-Ausch Veronika, Machherndl-Spandl Sigrid, Saini Olga, Wipplinger Dagmar, Kaynak Emine, Milanov Robert, Rotter Natalia, Hasengruber Petra, Mair Lorenz, Nikoloudis Alexander, Weltermann Ansgar, Rumpold Holger, Clausen Johannes
Аннотация
INTRODUCTION: Chromosome 1q abnormalities are among the most frequent cytogenetic alterations in multiple myeloma (MM), yet their prognostic relevance has been reported inconsistently and varies across current risk stratification models.
METHODS: We conducted a retrospective single-center study to evaluate the clinical impact of 1q abnormalities in 140 patients with newly diagnosed MM undergoing autologous stem cell transplantation (ASCT).
RESULTS: Fluorescence in situ hybridization at diagnosis identified 1q alterations in 40% of patients, including 1q gain (3 copies; 29.3%) and amplification (≥4 copies; 10.7%). Patients with 1q amplification had significantly shorter progression-free survival (PFS) compared to those without 1q abnormalities, whereas 1q gain was not associated with inferior outcomes. Notably, patients with co-occurring high-risk cytogenetic features ("double-hit") had the poorest outcomes, while isolated 1q alterations did not independently impact survival. Despite achieving deeper responses both prior to and at day 100 after ASCT, patients with 1q gain/amplification did not experience improved long-term outcomes, underscoring the limited prognostic value of response assessment at a single time point. In multivariable analyses, established risk factors, including ISS stage III and IMWG high-risk cytogenetics, remained independently associated with PFS and overall survival (OS), whereas 1q abnormalities did not, although the limited number of patients with 1q amplification warrants cautious interpretation. Maintenance therapy was associated with improved PFS but not OS.
CONCLUSION: In conclusion, the prognostic relevance of chromosome 1q alterations in transplant-eligible newly diagnosed MM appears to be primarily driven by copy number burden and co-occurrence with other high-risk lesions rather than by their isolated presence. These findings support the integration of 1q abnormalities into composite risk models to improve risk stratification.
METHODS: We conducted a retrospective single-center study to evaluate the clinical impact of 1q abnormalities in 140 patients with newly diagnosed MM undergoing autologous stem cell transplantation (ASCT).
RESULTS: Fluorescence in situ hybridization at diagnosis identified 1q alterations in 40% of patients, including 1q gain (3 copies; 29.3%) and amplification (≥4 copies; 10.7%). Patients with 1q amplification had significantly shorter progression-free survival (PFS) compared to those without 1q abnormalities, whereas 1q gain was not associated with inferior outcomes. Notably, patients with co-occurring high-risk cytogenetic features ("double-hit") had the poorest outcomes, while isolated 1q alterations did not independently impact survival. Despite achieving deeper responses both prior to and at day 100 after ASCT, patients with 1q gain/amplification did not experience improved long-term outcomes, underscoring the limited prognostic value of response assessment at a single time point. In multivariable analyses, established risk factors, including ISS stage III and IMWG high-risk cytogenetics, remained independently associated with PFS and overall survival (OS), whereas 1q abnormalities did not, although the limited number of patients with 1q amplification warrants cautious interpretation. Maintenance therapy was associated with improved PFS but not OS.
CONCLUSION: In conclusion, the prognostic relevance of chromosome 1q alterations in transplant-eligible newly diagnosed MM appears to be primarily driven by copy number burden and co-occurrence with other high-risk lesions rather than by their isolated presence. These findings support the integration of 1q abnormalities into composite risk models to improve risk stratification.