PO.CL12.01 · 临床研究

采用共识基因组分期(Consensus Genomic Staging)对CoMMpass研究中的多发性骨髓瘤进行风险分层，可识别出高非洲遗传血统与低非洲遗传血统患者之间的差异

Multiple myeloma risk classification of CoMMpass using Consensus Genomic Staging identifies differences between patients with high and low African genetic ancestry

编号 3887 展板 20 时间 4/20 02:00–05:00 区域 Section 46 主讲 Steven Foltz, BS;MS;PhD

分会场 Molecular Classification and Tumor Biology in Cancer

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作者与单位 Authors & Affiliations

Steven M. Foltz¹, Chaitanya R. Acharya¹, Alexander Gout¹, Yuxin Jin², David E. Avigan³, Ravi Vij⁴, Shaji Kunnathu Kumar⁵, Sagar Lonial⁶, Hearn Cho¹, Katie Wozniak¹, Jonathan J. Keats⁷, Craig Cole⁸, John D. Carpten⁹, George J. Mulligan¹

¹Multiple Myeloma Research Foundation, Norwalk, CT,²Beckman Research Institute of The City of Hope, Duarte, CA,³Beth Israel Deaconess Medical Center, Boston, MA,⁴Washington University School of Medicine, St. Louis, MO,⁵Mayo Clinic, Rochester, MN,⁶Emory Winship Cancer Institute, Atlanta, GA,⁷TGen (The Translational Genomics Research Institute), Phoenix, AZ,⁸Karmanos Cancer Institute, Detroit, MI,⁹City of Hope, Duarte, CA

摘要 Abstract

中文摘要

背景：多发性骨髓瘤是成人中第二常见的血液系统恶性肿瘤，尽管近期取得进展，但仍无法治愈。IMWG/IMS近期发布了更新的风险标准——共识基因组分期(Consensus Genomic Staging, CGS)，将基因组事件与临床指标相结合以识别高危患者(Avet-Loiseau等，JCO 2025)。我们将CGS风险标准应用于多发性骨髓瘤研究基金会CoMMpass研究(NCT01454297)的基线样本，该研究是一项前瞻性、纵向观察性研究，于2011-2017年间纳入了超过1100名受试者。方法：我们按照CGS标准评估患者风险。标准1：del(17p)，克隆比例阈值>20%，和/或TP53突变。标准2：IgH易位，包括t(4;14)、t(14;16)或t(14;20)，同时伴有1q+和/或del(1p32)。标准3：单等位基因del(1p32)伴1q+，或双等位基因del(1p32)。标准4：β2微球蛋白≥5.5 mg/L且肌酐正常。符合一项或多项标准的患者被归类为高危。为检验风险是否与遗传血统相关，我们将患者分为高非洲遗传血统组和低非洲遗传血统组。遗传血统采用ADMIXTURE并与1000 Genomes进行比较来测定。结果：我们评估了877例CoMMpass患者的CGS风险状态，发现69.2%(573/828)为标准风险(SR)，30.8%(255/828)为高危(HR)。HR患者的无进展生存期(中位PFS 26.3个月对42.5个月；log-rank检验，p < 0.0001)和总生存期(中位OS 63.9个月对中位未达到；p < 0.0001)均较差。10.6%(91/858)的患者符合标准1，10.7%(93/873)符合标准2，5.6%(49/877)符合标准3，8.7%(73/835)符合标准4。我们发现14.2%(123/867)的患者具有高非洲样遗传血统(AFR-high)，85.8%(744/867)具有低非洲样遗传血统(AFR-low)。我们观察到AFR-high组中的HR患者(20%，23/115)显著少于AFR-low组(32.4%，231/712)(Fisher精确检验，p = 0.0065)。AFR-high组在所有标准上符合HR标准的比例均较低，但仅在标准3上差异具有显著性(p值 = 0.03)。AFR-high患者较高的肌酐水平可能影响了其满足标准4中肌酐正常的要求。结论：HR患者占CoMMpass受试者的30.8%，其PFS和OS较SR患者显著更差。根据CGS标准，AFR-high患者符合HR标准的比例低于AFR-low患者。采用CGS标准确定患者入组资格的临床试验可能难以纳入具有代表性的患者群体，包括AFR-high患者。应仔细考量筛查和入组标准，以减轻潜在的入组差异。

查看英文原文 English abstract

Background: Multiple myeloma is the second most common adult blood cancer and remains incurable, despite recent advances. The IMWG/IMS recently published updated risk criteria, Consensus Genomic Staging (CGS), combining genomic events with clinical measures to identify high-risk patients (Avet-Loiseau, et al. JCO 2025). We applied CGS risk criteria to baseline samples from the Multiple Myeloma Research Foundation CoMMpass Study (NCT01454297), a prospective, longitudinal observational study that enrolled more than1100 participants between 2011-2017. Methods: We assessed patient risk following CGS criteria. Criteria 1: del(17p), with a cutoff of >20% clonal fraction, and/or TP53 mutation. Criteria 2: an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32). Criteria 3: monoallelic del(1p32) along with 1q+ or biallelic del(1p32). Criteria 4: beta-2 microglobulin >= 5.5 mg/L with normal creatinine. Patients meeting one or more criteria were classified as High Risk. To test if risk showed association with genetic ancestry, we grouped patients into those with high African genetic ancestry and those with low African genetic ancestry. Genetic ancestry was measured using ADMIXTURE in comparison to 1000 Genomes. Results: We evaluated the CGS risk status of 877 CoMMpass patients, finding 69.2% (573/828) to be Standard Risk (SR) and 30.8% (255/828) to be High Risk (HR). HR patients showed worse progression-free survival (median PFS 26.3 months vs. 42.5 months; log rank test, p < 0.0001) and overall survival (median OS 63.9 months vs. median not reached; p < 0.0001). 10.6% (91/858) of patients met Criteria 1, 10.7% (93/873) met Criteria 2, 5.6% (49/877) met Criteria 3, and 8.7% (73/835) met Criteria 4. We found 14.2% (123/867) of patients to have high African-like genetic ancestry (AFR-high) and 85.8% (744/867) to have low African-like genetic ancestry (AFR-low). We observed significantly fewer HR patients within the AFR-high group (20%, 23/115) than in the AFR-low group (32.4%, 231/712) (Fisher's exact test, p = 0.0065). The AFR-high group met HR criteria at a lower rate across all criteria, but only with Criteria 3 was the difference significant (p-value = 0.03). Higher levels of creatinine in AFR-high patients may have impacted meeting the normal creatinine requirement of Criteria 4. Conclusions: HR patients comprise 30.8% of CoMMpass subjects and show significantly worse PFS and OS than SR patients. AFR-high patients met HR criteria at a lower rate than AFR-low patients according to the CGS criteria. Clinical trials that utilize CGS criteria to determine patient eligibility may be challenged to enroll a representative patient population, including AFR-high patients. Screening and eligibility criteria should be carefully considered to mitigate potential enrollment disparities.

利益披露 Disclosure

S. M. Foltz, None.. C. R. Acharya, None.. A. Gout, None.. Y. Jin, None.. D. E. Avigan, None.. R. Vij, None.. S. K. Kumar, None.. S. Lonial, None.. H. Cho, None.. K. Wozniak, None.. J. J. Keats, None.. C. Cole, None.. J. D. Carpten, None.. G. J. Mulligan, None.

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