Circulating tumor DNA (ctDNA) can be used to predict outcomes of axicabtagene ciloleucel (axi-cel) treatment in patients with large B-cell lymphoma, according to research published in the Journal of Clinical Oncology.
The study authors noted that a majority of patients respond to axi-cel, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, but many of those patients eventually relapse.
In a prospective, multicenter study, researchers investigated the prognostic value of ctDNA monitoring before and after axi-cel treatment.
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The study included 72 patients — 49 with diffuse large B-cell lymphoma, 17 with transformed follicular lymphoma, and 6 with primary mediastinal B-cell lymphoma.
There were 69 patients (96%) who had adequate DNA to permit tracking of tumor clonotype.
One of the study’s key endpoints was to determine if ctDNA-based assessments at the start of lymphodepletion (pre-LD) could predict progression-free survival (PFS) with at least a 6-month follow-up.
Results showed that patients with pre-LD ctDNA concentrations below 10 lymphoma genomes per mL (LG/mL) or 10-100 LG/mL had significantly better PFS and overall survival (OS) than patients with pre-LD ctDNA concentrations above 100 LG/mL.
The researchers also found that patients with higher pretreatment ctDNA concentrations were not only more likely to experience disease progression. They were also more likely to have grade 2 or higher cytokine release syndrome and grade 2 or higher immune effector cell-associated neurotoxicity syndrome.
Another key endpoint of the trial was to determine if ctDNA-based minimal residual disease (MRD) assessments on day 28 could predict PFS.
The median PFS was 3 months in patients who were MRD positive (any detectable ctDNA) on day 28 and was not reached in patients who were MRD negative on day 28 (P <.0001). The median OS was 19 months and not reached, respectively (P =.0080).
Among patients with a radiographic partial response or stable disease on day 28, relapse was observed in 1 of 10 patients who had undetectable ctDNA and in 15 of 17 patients who had detectable ctDNA (P =.0001).
Nearly all patients who relapsed (29 of 30) had detectable ctDNA at or before radiographic relapse. Patients with a durable response to axi-cel had undetectable ctDNA at or before 3 months after axi-cel infusion.
“ctDNA appears to predict progression after CAR-T therapy and should be incorporated as an integral biomarker in future trials of consolidation therapy after CAR-T to prevent relapse,” the study authors wrote.
“[T]o our knowledge, this is the first study to comprehensively evaluate ctDNA dynamics prospectively in patients undergoing CAR therapy. ctDNA-based surveillance of patients with LBCL [large B-cell lymphoma] undergoing axi-cel may be a useful adjunct to radiographic assessments of disease status.”
Disclosures: This research was supported by the National Cancer Institute and others. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Frank MJ, Hossin NM, Bukhari A, et al. Monitoring of circulating tumor DNA improves early relapse detection after axicabtagene ciloleucel infusion in large B-cell lymphoma: results of a prospective multi-institutional trial. J Clin Oncol. Published online June 16, 2021. doi:10.1200/JCO.21.00377
