Co-Occurrence of High-Risk Cytogenetic Abnormalities as a Predictive Marker for Multiple Myeloma
The presence of 2 or more high-risk cytogenetic abnormalities (HRCAs) among patients with newly diagnosed (NDMM) and relapsed/refractory (R/ R) multiple myeloma (MM) was associated with worse survival outcomes, according to study results published in Journal of Clinical Oncology.
Accurate and consistent identification of high-risk disease remains a clinical priority as disparities in survival outcomes remain varied among patients with MM. Researchers aimed to evaluate the prognostic impact of co-occurring HRCAs across disease stages and therapies in a systematic review. The primary outcomes were hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS).
At analysis, 24 trials were included with 13,926 patients of which 7,724 reported having co-occurring HRCAs. Of patients with HRCA co-occurrence, 4,106 patients had transplant-eligible (TE) NDMM, 1,816 had transplant-ineligible newly diagnosed MM (TNE) NDMM, and 1,802 had R/R MM. Among all patients, the median age was 66.5 years (interquartile range, 59 to 72) and were mostly male (56.5%).
Patients with co-occurring HRCAs HR for PFS (2.28; 95% confidence interval [CI], 2.05 to 2.54) and OS (2.94; 95% CI, 2.49 to 3.47), compared to patients with 1 HRCA (PFS HR, 1.51; 95% CI, 1.38 to 1.65; OS HR, 1.69; 95% CI, 1.52 to 1.88). These findings remained consistent in trials initiated since 2015 (PFS HR, 2.39; 95% CI, 1.96 to 2.91; OS HR, 3.10; 95% CI, 2.10 to 4.60).
In the subgroup analysis, prognostic effect size was highest in patients with TE NDMM (PFS HR, 2.53; 95% CI, 2.26 to 2.84; OS HR, 4.17; 95% CI, 3.34 to 5.22), compared to both TNE NDMM (PFS HR, 1.97; 95% CI, 1.55 to 2.50; OS HR, 2.31; 95% CI, 1.92 to 2.78) and R/R MM (PFS HR, 2.05; 95% CI, 1.66 to 2.54; OS HR, 2.21; 95% CI, 1.83 to 2.67).
“In conclusion, co-occurrence of cytogenetic abnormalities is associated with poor prognosis in patients with MM,” the researchers concluded.
“This association is consistent in key patient subgroups and across widely accessible treatment modalities, across TE NDMM and RRMM, supporting improved access to testing and reporting of risk marker co-occurrence across patient groups,” they added.
Source:
Kaiser MF, Sonneveld P, Cairns DA, et al. Cooccurrence of cytogenetic abnormalities and high-risk disease in newly diagnosed and relapsed/refractory multiple myeloma. Journal of Clinical Oncology. Published online February 18, 2025. doi: 10.1200/jco-24-01253
