ctDNA is a Possible Prognostic Tool for Predicting DLBCL Outcomes

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

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

“The conclusion was that [ctDNA use] can be implemented and can predict the outcome [in patients with DLBCL],” said ESMO discussant Irit Avivi, MD, director of the Division of Hematology at Tel Aviv Sourasky Medical Center. “This might be a tool to follow the patients [with DLBCL] after treatment in most of the patients, but not in all of them, at least not with this 59-gene panel, [but] there are panels which include more genes.”

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

“ctDNA is really becoming a very important tool in our practice during research, but I believe that in 1 to 3 years, it’s going to be used routinely,” Avivi commented.

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

A total of 172 patients with newly diagnosed DLBCL who underwent genetic testing with a 59-gene next-generation sequencing (NGS) panel were included in the study.

Prior to treatment, ctDNA was detected in 74.4% of patients.

The most frequent gene mutations observed were PCLO in 33.6% of patients and PIM1 in 32.8%. Mutations in KMT2D, CREBBP, BCL2, TP53, KLHL6, and MYC genes were much more common in germinal center B-cell (GCB) disease (P = .012; P = .011; P = .036; P = .020; and P = .0056), whereas CD79B was more common in non-GCB patients (P = .023). Avivi noted that research has shown that CD79B has been associated with extranodal disease and non-GCB subtype.

ctDNA VAF prior to treatment was found to correlate with International Prognostic Index (IPI) and Ann Arbor disease stage.

“The VAF was found to be in correlation with the IPI and the stage, which is also not surprising. If you have higher VAF levels, your outcome is going to be worse, and IPI is also a very strong predictor for worse outcomes,” Avivi said. “We know that in patients with solid tumors, higher VAF burden is associated usually with a worse outcome, which is also true for DLBCL.”

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

“I’m asking myself, is it really valuable nowadays because everything was in correlation with very simple clinical prognostic factors,” Avivi concluded. “Is [there] going to be more value in predicting patient’s outcome? I don’t know.”

Reference

Guan T, Zhang M, Su L. Retrospective analysis of clinical value of ctDNA in newly diagnosed diffuse large B-cell lymphoma. Ann Oncol. 2022;33(suppl 7):S808-S869. doi:10.1016/annonc/annonc1089