McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO.
Department of Surgery, Washington University School of Medicine, St Louis, MO.
JCO Precis Oncol. 2021 Jan 14;5. doi: 10.1200/PO.20.00182. eCollection 2021.
Physicians treating hematologic malignancies increasingly order targeted sequencing panels to interrogate recurrently mutated genes. The precise impact of these panels on clinical decision making is not well understood.
Here, we report our institutional experience with a targeted 40-gene panel (MyeloSeq) that is used to generate a report for both genetic variants and variant allele frequencies for the treating physician (the limit of mutation detection is approximately one AML cell in 50).
In total, 346 sequencing reports were generated for 325 patients with suspected hematologic malignancies over an 8-month period (August 2018 to April 2019). To determine the influence of genomic data on clinical care for patients with acute myeloid leukemia (AML), we analyzed 122 consecutive reports from 109 patients diagnosed with AML and surveyed the treating physicians with a standardized questionnaire. The panel was ordered most commonly at diagnosis (61.5%), but was also used to assess response to therapy (22.9%) and to detect suspected relapse (15.6%). The panel was ordered at multiple timepoints during the disease course for 11% of patients. Physicians self-reported that 50 of 114 sequencing reports (44%) influenced clinical care decisions in 44 individual patients. Influences were often nuanced and extended beyond identifying actionable genetic variants with US Food and Drug Administration-approved drugs.
This study provides insights into how physicians are currently using multigene panels capable of detecting relatively rare AML cells. The most influential way to integrate these tools into clinical practice will be to perform prospective clinical trials that assess patient outcomes in response to genomically driven interventions.
治疗血液系统恶性肿瘤的医生越来越多地订购靶向测序面板来检测频繁突变的基因。这些面板对临床决策的确切影响尚不清楚。
在这里,我们报告了我们机构使用靶向 40 基因面板(MyeloSeq)的经验,该面板用于为治疗医生生成一份报告,其中包括遗传变异和变异等位基因频率的报告(检测突变的极限约为每 50 个 AML 细胞中有一个)。
在 2018 年 8 月至 2019 年 4 月的 8 个月期间,共为 325 名疑似血液系统恶性肿瘤患者生成了 346 份测序报告。为了确定基因组数据对急性髓系白血病(AML)患者临床治疗的影响,我们分析了 109 名诊断为 AML 的患者的 122 份连续报告,并对治疗医生进行了标准化问卷调查。该面板最常在诊断时订购(61.5%),但也用于评估治疗反应(22.9%)和检测疑似复发(15.6%)。在 11%的患者中,该面板在疾病过程中的多个时间点被订购。医生们自我报告说,在 114 份测序报告中有 50 份(44%)在 44 名个别患者中影响了临床护理决策。这些影响通常很微妙,并且超出了识别具有美国食品和药物管理局批准药物的可操作遗传变异。
本研究深入了解了医生目前如何使用能够检测到相对罕见的 AML 细胞的多基因面板。将这些工具整合到临床实践中的最有效方法将是进行前瞻性临床试验,评估患者对基于基因组的干预的反应。