ctDNA is a potential prognostic tool for predicting DLBCL outcomes

A presentation at ESMO 2022 explains the use of tumor DNA as a tool that can predict the outcome of patients with diffuse B-cell lymphoma.

Circulating tumor DNA (ctDNA) levels can be used as a prognostic factor and tumor-specific biomarker for metastatic large B-cell lymphoma (DLBCL) in China, according to the results of a retrospective analysis presented at the European Society of Medical Oncology (ESMO) 2022 conference.

In addition, in the study, pretreatment ctDNA variant allele frequency (VAF) levels were successfully used to predict response rate, progression-free survival (PFS), and overall survival (OS), which was found to be in line with what was done. It is seen in solid tumors.

“The conclusion was that [ctDNA use] It can be implemented and can predict the outcome [in patients with DLBCL]ESMO spokeswoman Irit Avivi, director of the division of hematology at Tel Aviv Sourasky Medical Center, said. “This could be a tool for patient follow-up [with DLBCL] After treatment in most, but not all patients, at least not with this 59-gene panel, [but] There are panels with more genes.”

Currently in hematological malignancies, ctDNA is mostly used as a marker for minimal residual disease. However, DLBCL is a heterogeneous disease and requires prognostic methods.

“ctDNA has really become a very important tool in our practice during research, but I think within 1 to 3 years, it will be used routinely,” Avivi commented.

The study authors, led by lead author Tao Guan, MD, of the Department of Hematology, Shanxi Provincial Cancer Hospital, Taiyuan, China, sought to determine whether ctDNA could be used to predict outcomes in DLBCL patients, as noted. In solid tumors selected to date. Guan et al also sought to identify mutations typical of DLBCL subtypes.

A total of 172 patients with newly diagnosed DLBCL who underwent genetic testing using a 59-gene Next Generation Sequencing (NGS) panel were included in the study.

Before treatment, ctDNA was detected in 74.4% of patients.

The most common genetic mutations observed were PCLO In 33.6% of patients and PIM1 at 32.8%. mutations in KMT2D, CREBBP, BCL2, TP53, KLHL6, And the MYC The genes were more common in germ cell B (GCB) disease (s = .012; s = .011; s = .036; s = .020; And the s = .0056), while CD79B It was more common in non-GCB patients (s = .023). Avivi pointed out that research has shown this CD79B Associated with extracorporeal disease and non-GCB subtype.

ctDNA VAF before treatment was found to correlate with the international prognostic index (IPI) and stage of Ann Arbor disease.

“VAF has been found to be in association with IPI and stage, which is also not surprising. If you have higher levels of VAF, your outcome will be worse, and IPI is also a very strong predictor of worse outcomes,” said Avivi. “We know that in patients with solid tumors, a high VAF burden is typically associated with a worse outcome, which is also true for DLBCL.”

Increased levels of VAF were associated with increased levels of lactate dehydrogenase (s <.0001), bone marrow injury (s = .0277), massive disease (s = .0047), all of which are poor prognostic factors in DLBCL. Shorter PFS and OS were seen in all patients with VAF levels of ctDNA above 23% compared with those with lower levels of VAF. Correlation with VAF and OS levels was considered significant.

“I ask myself, is it really valuable nowadays because everything is related to very simple clinical predictive factors,” Avivi concluded. “he is [there] Will it be more valuable in predicting patient outcomes? I don’t know.”

reference
Guan T, Zhang M, Su L. Retrospective analysis of the clinical value of ctDNA in newly diagnosed diffuse B-cell lymphoma. Ann Oncol. 2022; 33 (Supplement 7): S808-S869. doi: 10.1016/ununk/ununk 1089

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