NEW YORK – Analyzing circulating tumor DNA could help predict which newly diagnosed lymphoma patients might benefit from adding Roche's bispecific antibody Columvi (glofitamab) to a first-line chemotherapy regimen, according to data from a Phase II trial presented at the American Society of Hematology's annual meeting on Monday.

纽约——根据周一美国血液学会年会上公布的一项II期临床试验数据，分析循环肿瘤DNA有助于预测哪些新诊断的淋巴瘤患者可能会从罗氏双特异性抗体Columvi（glofitamab）加入一线化疗方案中受益。

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Lorenzo Falchi, a lymphoma oncologist at Memorial Sloan Kettering, presented results from the study, in which patients with large B-cell lymphoma (LBCL) defined as high-risk based on circulating tumor DNA (ctDNA) testing, received Columvi in addition to the commonly prescribed first-line chemotherapy-containing regimen R-CHOP.

纪念斯隆·凯特林（Memorial Sloan Kettering）的淋巴瘤肿瘤学家洛伦佐·法尔基（Lorenzo Falchi）介绍了这项研究的结果，根据循环肿瘤DNA（ctDNA）检测，大B细胞淋巴瘤（LBCL）患者被定义为高风险，除了常用的含有R-CHOP方案的一线化疗外，还接受了Columvi治疗。

As Falchi explained in his presentation, R-CHOP, comprising Biogen and Genentech's monoclonal antibody Rituxan (rituximab) and cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone, can be curative on its own or at least lead to long-term remissions in two-thirds of newly diagnosed LBCL patients.

正如Falchi在他的演讲中所解释的那样，R-CHOP包括Biogen和Genentech的单克隆抗体利妥昔单抗（利妥昔单抗）和环磷酰胺，羟基柔红霉素，oncovin和泼尼松，可以单独治愈，或者至少导致三分之二的新诊断LBCL患者的长期缓解。

But identifying the one-third who won't benefit from R-CHOP alone has been challenging for oncologists. .

但是，对于肿瘤学家来说，确定三分之一不能单独从R-CHOP中受益的人一直是一个挑战。

'There is an unmet need in this space, and ctDNA testing could be an accurate, noninvasive tool to monitor the dynamics of tumor response and potentially identify high-risk patients who will have a suboptimal response to chemotherapy and a worse outcome,' Falchi said. 'With this background in mind, we thought [Columvi] could be a potential tool to overcome some of these adverse prognostic factors.'.

Falchi说：“这一领域的需求尚未得到满足，ctDNA检测可能是一种准确、无创的工具，可以监测肿瘤反应的动态，并有可能识别对化疗反应不佳且预后较差的高危患者。”考虑到这一背景，我们认为[哥伦比亚]可能是克服这些不良预后因素的潜在工具。”。

Columvi, which is a CD20- and CD3-directed bispecific antibody, is designed to engage and redirect T cells to attack and kill cancerous B cells. As a monotherapy, its benefit has been established in heavily pretreated lymphoma patients, and earlier this year, it netted accelerated approval from the US Food and Drug Administration as treatment for third- or later-line lymphoma patients.

Columvi是一种CD20和CD3定向的双特异性抗体，旨在吸引和重定向T细胞以攻击和杀死癌B细胞。作为一种单一疗法，它的益处已经在经过严重预处理的淋巴瘤患者中确立，今年早些时候，它获得了美国食品和药物管理局的加速批准，用于治疗三线或更高级别的淋巴瘤患者。

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In the study presented at the meeting, Falchi and colleagues enrolled patients with CD20-positive LBCL. Using Avenio Oncology's next-generation sequencing assay for non-Hodgkin lymphoma, they analyzed patients' ctDNA at baseline, then again at the end of their first and second cycles of R-CHOP. They determined that patients were at high risk of relapse when they had less than a 100-fold reduction in ctDNA at the end of the first cycle.

在会议上提出的研究中，Falchi及其同事招募了CD20阳性LBCL患者。他们使用Avenio Oncology针对非霍奇金淋巴瘤的下一代测序分析方法，在基线时分析患者的ctDNA，然后在第一个和第二个R-CHOP周期结束时再次分析。他们确定，当患者在第一个周期结束时ctDNA减少不到100倍时，患者复发的风险很高。

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For these high-risk patients, Falchi and colleagues added Columvi to the treatment regimen beginning with the third R-CHOP cycle.

对于这些高危患者，Falchi及其同事从第三个R-CHOP周期开始将Columvi添加到治疗方案中。

Out of 115 patients, 29 had high-risk LBCL according to the prespecified criteria and 70 had low-risk disease. Sixteen patients from this group could not have their ctDNA tested due to various reasons such as a missing germline sample or workflow problems. Most of these problems limiting ctDNA analysis have since been addressed — for instance, by requiring additional peripheral blood mononuclear cells — and Falchi expressed confidence that similar problems wouldn't occur if the study were repeated today. .

在115例患者中，根据预先设定的标准，29例患有高危LBCL，70例患有低危疾病。由于各种原因，例如缺少种系样本或工作流程问题，该组的16名患者无法进行ctDNA检测。限制ctDNA分析的大多数问题已经得到解决-例如，通过需要额外的外周血单核细胞-Falchi表示相信，如果今天重复这项研究，类似的问题不会发生。。

Investigators then tracked how many of the 29 high-risk LBLC patients responded once Columvi was added to R-CHOP. Although researchers are still following patients, Falchi reported 'encouraging' early data that 95 percent of patients had an objective response to Columvi plus R-CHOP and 60 percent had a complete metabolic response, which increased to 85 percent of patients by the end of treatment.

然后，研究人员追踪了29名高危LBLC患者中有多少人在Columvi加入R-CHOP后有反应。尽管研究人员仍在跟踪患者，但Falchi报告的早期数据“令人鼓舞”，即95%的患者对Columvi加R-CHOP有客观反应，60%的患者有完全代谢反应，到治疗结束时，这一比例增加到85%。

Despite the limited follow-up, the responses were durable, according to Falchi. .

Falchi说，尽管后续行动有限，但反应是持久的。

In terms of Columvi and R-CHOP's safety and tolerability, around three-quarters of patients experienced adverse events related to Columvi, but just nine patients experienced grade 3 or 4 toxicities and none of the patients died on the study. Other than cytokine release syndrome, which affected one-fifth of Columvi-treated patients and were mostly low grade, Falchi said that the combination treatment's toxicity profile was similar to standard R-CHOP..

就Columvi和R-CHOP的安全性和耐受性而言，大约四分之三的患者经历了与Columvi相关的不良事件，但只有9名患者经历了3或4级毒性，并且没有患者在研究中死亡。Falchi说，除了影响五分之一接受Columvi治疗的患者且大多为低度的细胞因子释放综合征外，联合治疗的毒性特征与标准R-CHOP相似。。

'In this early, limited experience, coming from an international Phase II study, we proved that ctDNA assessment is feasible on an on-treatment basis for patients with frontline, diffuse B-cell lymphoma,' Falchi said. The high response rates observed, he noted, 'compared favorably' to a population of patients with high-risk ctDNA who'd been treated with R-CHOP alone in an earlier Roche study dubbed POLARIX.

Falchi说：“在一项国际II期研究的早期有限经验中，我们证明了ctDNA评估在一线弥漫性B细胞淋巴瘤患者的治疗基础上是可行的。”。他指出，观察到的高反应率与罗氏早期一项称为POLARIX的研究中单独使用R-CHOP治疗的高危ctDNA患者相比“有利”。

In that study, he noted, patients had a complete response rate of 68 percent. .

他指出，在这项研究中，患者的完全缓解率为68%。

Based in part on these encouraging data, he said that Roche is comparing the activity of first-line Columvi plus R-CHOP against R-CHOP in large B-cell lymphoma patients in a Phase III randomized trial.

部分基于这些令人鼓舞的数据，他说，罗氏正在一项III期随机试验中比较大型B细胞淋巴瘤患者一线Columvi加R-CHOP与R-CHOP的活性。