Новая генетическая система стадирования выявляет пациентов с множественной миеломой в группе сверхвысокого риска

The new International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) consensus genomic staging (CGS) system effectively identifies patients with newly diagnosed multiple myeloma (MM) at high risk for poor outcomes despite treatment with contemporary regimens, according to findings published in HemaSphere. “Prognostication systems such as the International Staging System (ISS) and its subsequent revisions, the Revised International Staging System (R‐ISS) and its update (R2‐ISS), have been widely adopted for risk stratification and treatment planning in clinical practice; however, these models were largely derived and validated in cohorts treated with earlier‐generation therapies, which may limit their relevance in the era of novel combinations and immunotherapies,” the study authors explained in their report. “As our knowledge in the biology and genetics of MM expands, new genetic lesions have emerged as significant prognostic factors; moreover, sensitive tools are now widely available (such as NGS) and are routinely used in many hematologic malignancies providing valuable prognosis and predictive information,” the study authors added. The CGS was developed to refine the classification of high-risk disease by placing greater emphasis on genomic and cytogenetic features while retaining limited consideration of biochemical markers. The system was derived primarily from large clinical trial cohorts but had not yet been validated in large, independent patient populations. The investigators evaluated the CGS criteria among consecutive patients with newly diagnosed MM who were treated at a tertiary academic center in Greece between 2010 and 2024. All patients had complete clinical and fluorescence in situ hybridization (FISH)-based cytogenetic data required for CGS classification, although TP53 mutational status was unavailable for most patients. High-risk disease was defined by del(17p), specified combinations of immunoglobulin heavy-chain translocations and chromosome 1 abnormalities, qualifying chromosome 1 abnormalities, or serum β2-microglobulin ≥5.5 mg/L in patients with preserved renal function. The analysis included 1209 patients (56% men; median age, 68 years). At diagnosis, 35% had serum creatinine ≥1.2 mg/dL. Treatment included triplet induction therapy in 85% of patients and anti-CD38–based regimens in 20%, while 29% underwent autologous stem cell transplantation. Overall, 25.2% of patients were classified as having high-risk MM according to the new CGS criteria. At a median follow-up of 5.25 years, the median overall survival (OS) was 44 months among patients with high-risk MM compared with 93 months among those with standard-risk MM (hazard ratio [HR], 1.81; 95% CI, 1.51-2.20; P <.001). The 5-year OS rates were 40% and 61%, respectively. The median progression-free survival (PFS) was also significantly shorter among those with high-risk MM (21.3 vs 36 months; HR, 1.64; 95% CI, 1.40-1.90; P <.001). The current large study in consecutive patients not only validates the utility of the new CGS but also enhances its generalizability in daily clinical practice. The number of high-risk features further differentiated outcomes. A total of 53 patients (4.4% of the overall cohort) had ≥2 high-risk features and comprised an ultra-high-risk group. The median OS was 25 months among these patients compared with 52 months among those with only 1 high-risk feature (P <.001), corresponding to a 90% higher risk of death (HR, 1.90; 95% CI, 1.30-2.80; P =.001). Compared with patients with standard-risk MM, those with ≥2 high-risk features had approximately 3 times the risk of death (HR, 3.10; 95% CI, 2.20-4.20; P <.001). The CGS remained prognostic among patients with and without renal dysfunction and across treatment eras and transplantation status. Among patients who underwent autologous stem cell transplantation, high-risk CGS status was associated with worse OS (HR, 2.40; 95% CI, 1.50-4.00; P =.004), and an adverse association was also observed among patients who did not undergo transplantation (HR, 1.60; 95% CI, 1.40-2.00; P <.001). “In conclusion, the current large study in consecutive patients not only validates the utility of the new CGS but also enhances its generalizability in daily clinical practice,” the investigators concluded in their report. “Our findings demonstrate that the IMS/IMWG consensus CGS effectively complements and extends prior MM staging systems by recognizing both a high- and an ultra-high-risk population, even in the era of novel therapeutics.” Limitations of the study included lack of TP53 mutation data, assessment of chromosome 1p abnormalities using FISH rather than next-generation sequencing, and the single-center study design. The investigators noted that these limitations prevented full adherence to the strict CGS definition. Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. This article originally appeared on Hematology Advisor