Researchers found that patients who responded to treatment had a larger decline in ctDNA after 1 cycle of therapy (or 3 weeks) than patients who did not respond. The correlation was independent of line or type of therapy. Patients who achieved EMR or MMR had better EFS than patients who did not, a trend seen in both validation sets. However, EMR and MMR were associated with overall survival only in validation set 1.

The ctDNA dynamics after treatment initiation were “much more predictive” than pretreatment ctDNA levels, co-senior author Ash Alizadeh, MD, PhD, associate professor of medicine at Stanford University, told Cancer Therapy Advisor.


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A multivariate analysis showed that ctDNA dynamics were independent of other prognostic factors, including International Prognostic Index and interim positron emission tomography/computed tomography (PET/CT) scan. Also, when ctDNA dynamics were combined with interim PET/CT scans, prognostic ability strengthened: Patients who achieved a promising molecular response and PET/CT scan had further improved outcomes. “Both ctDNA and [PET/CT] scans have some information, but when you put them together, you get to be a little bit smarter [than if you were] using each one in isolation,” concluded Dr Alizadeh.

Studies are currently underway to determine whether ctDNA is also prognostic for patients receiving chimeric antigen receptor T-cell therapy, such as tisagenlecleucel, which gained US Food and Drug Administration approval for relapsed/refractory DLBCL in May 2018.

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The researchers of the current study are also planning a clinical trial to evaluate the clinical utility of the study results, but exactly what questions the trial will be designed to answer has not yet been determined. “As with any clinical study that involves many centers, there are lots of opinions about how that should shake out,” said Dr Alizadeh. “We’re trying to work through that right now.”

Disclosures: Dr Alizadeh disclosed financial relationships with CiberMed, Forty Seven, Janssen Oncology, Celgene, Roche/Genentech, and Gilead Sciences. He also reported patent filings on ctDNA detection assigned to Stanford University.

Reference

  1. Kurtz DM, Scherer F, Jin MC, et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma [published online August 20, 2018]. J Clin Oncol. doi: 10.1200/JCO.2018.78.5246