Therapeutic advances in medical oncology · 2024
Longitudinal genetically detectable minimal residual disease by fluorescence in situ hybridization confers a poor prognosis in myeloma.
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Cui Jian, Yu Tengteng, Lv Rui, Liu Jiahui, Fan Huishou, Yan Wenqiang, Xu Jingyu, Du Chenxing, Deng Shuhui, Sui Weiwei, Ho Matthew, Xu Yan, Anderson Kenneth C, Dong Xifeng, Qiu Lugui, An Gang
Аннотация
BACKGROUND: Deeper depth of response (DpR) after induction therapy, especially gain of negative minimal residual disease (MRD), has been linked to prolonged survival in multiple myeloma (MM). However, flow-MRD examination focuses on the numbers but not on the biological characteristics of residual plasma cells (PCs).
OBJECTIVES: To explore whether the genetic features of residual tumor cells affect the survival time of patients with MM.
DESIGN: A retrospective cohort study.
METHODS: We investigated the clonality of cytogenetic abnormalities (CAs) of the residual PCs using interphase fluorescence in situ hybridization (iFISH) in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Here, a longitudinal cohort of 269 patients with patient-paired diagnostic and post-induction iFISH results was analyzed.
RESULTS: Persistent CAs after induction therapy were detected in about half of the patients (118/269, 43%), and patients with undetectable CAs showed significantly improved survival compared with those with genetically detectable MRD [median progression-free survival (mPFS): 59.7 versus 35.7 months, p < 0.001; median overall survival (mOS): 97.1 versus 68.8 months, p = 0.011]. In addition, different patterns of therapy-induced clonal evolution were observed by comparing the clonal structure of residual PCs with paired baseline samples. Patients who maintained at a high risk during follow-up had the worst survival (mPFS: 30.5 months; mOS: 54.4 months), while those who returned to lower risk or had iFISH- at both time points had the best survival (mPFS: 62.0 months, mOS: not reached).
CONCLUSION: These findings highlighted the prognostic value of genetic testing in residual tumor cells, which may provide a deep understanding of clonal evolution and guide clinical therapeutic strategies.
OBJECTIVES: To explore whether the genetic features of residual tumor cells affect the survival time of patients with MM.
DESIGN: A retrospective cohort study.
METHODS: We investigated the clonality of cytogenetic abnormalities (CAs) of the residual PCs using interphase fluorescence in situ hybridization (iFISH) in the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199). Here, a longitudinal cohort of 269 patients with patient-paired diagnostic and post-induction iFISH results was analyzed.
RESULTS: Persistent CAs after induction therapy were detected in about half of the patients (118/269, 43%), and patients with undetectable CAs showed significantly improved survival compared with those with genetically detectable MRD [median progression-free survival (mPFS): 59.7 versus 35.7 months, p < 0.001; median overall survival (mOS): 97.1 versus 68.8 months, p = 0.011]. In addition, different patterns of therapy-induced clonal evolution were observed by comparing the clonal structure of residual PCs with paired baseline samples. Patients who maintained at a high risk during follow-up had the worst survival (mPFS: 30.5 months; mOS: 54.4 months), while those who returned to lower risk or had iFISH- at both time points had the best survival (mPFS: 62.0 months, mOS: not reached).
CONCLUSION: These findings highlighted the prognostic value of genetic testing in residual tumor cells, which may provide a deep understanding of clonal evolution and guide clinical therapeutic strategies.