Circulating Tumor DNA May Predict Results of CAR T-Cell Therapy in Large B Cell Lymphoma

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Circulating tumor DNA (ctDNA) can be used to predict the outcome of treatment with axicabtagene ciloleucel (axi-cel) in patients with large B-cell lymphoma, according to a study published in the Journal of Clinical Oncology.

The study authors noted that a majority of patients respond to axi-cel, a chimeric anti-CD19 antigen receptor (CAR) T cell therapy, but many of these patients relapse eventually.

In a prospective multicenter study, researchers investigated the prognostic value of cDNA 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 allow follow-up of the tumor clonotype.

One of the main endpoints of the study was to determine whether ctDNA-based assessments at onset of lymphodepletion (pre-LD) could predict progression-free survival (PFS) with follow-up of at least 6 months.

The results showed that patients with pre-LD cDNA concentrations of less than 10 lymphoma genomes per mL (LG / mL) or 10-100 LG / mL had significantly better PFS and overall survival (OS) than patients. patients with pre-LD cDNA concentrations greater than 100 LG / ml.

The researchers also found that patients with higher pre-treatment cDNA concentrations were not only more likely to experience disease progression. They were also more likely to have grade 2 or greater cytokine release syndrome and grade 2 or greater immune effector cell neurotoxicity syndrome.

Another key endpoint of the trial was whether the cDNA-based minimal residual disease (MRD) assessments at day 28 could predict PFS.

Median PFS was 3 months in MRD positive patients (any detectable ctDNA) on day 28 and was not achieved in MRD negative patients on day 28 (P <.0001 median os was months and not reached respectively>P = .0080).

Among patients with a partial radiographic response or stable disease on day 28, relapse was observed in 1 of 10 patients who had undetectable cDNA and in 15 of 17 patients who had detectable cDNA (P = .0001).

Almost all of the patients who relapsed (29 of 30) had detectable ctDNA at or before the radiographic relapse. Patients with a sustained 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 relapses,” wrote the study authors.

“[T]To our knowledge, this is the first study to comprehensively assess cDNA dynamics prospectively in patients receiving CAR therapy. CDNA-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 reported 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 detection of relapses after axicabtagene ciloleucel infusion in large B-cell lymphoma: results from a prospective multi-institutional trial. J Clin Oncol. Published online June 16, 2021. doi: 10.1200 / JCO.21.00377

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