In a prospective study reported in the Journal of Clinical Oncology, Frank et al found that monitoring of circulating tumor DNA (ctDNA) improved detection of early relapse after axicabtagene ciloleucel infusion in patients with relapsed or refractory large B-cell lymphoma.
Study Details
A total of 72 patients were enrolled at Stanford University, Moffitt Cancer Center, and the University of Maryland Medical Center between January 2018 and May 2019 prior to lymphodepleting chemotherapy and standard-of-care axicabtagene ciloleucel treatment. ctDNA sequences were frequently monitored using next-generation sequencing from the time of starting lymphodepleting chemotherapy until disease progression or for up to 1 year after axicabtagene ciloleucel infusion.
In the study, the overall response rate was 84.7%; the complete response rate was 63.9%; the median progression-free survival was 10.3 months; median duration of response was not reached, with 79.5% of responses maintained at 1 year; and median overall survival was not reached, with a 1-year rate of 71.2%.
Noninvasive ctDNA assessments can risk-stratify and predict outcomes of patients undergoing axi-cel for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.— Frank et al
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Key Findings
A tumor clonotype was successfully detected in 69 (96%) of the 72 patients.
Patients with pretreatment ctDNA concentration < 10 LG/mL and 10 to 100 LG/mL had 1-year progression-free survival of 78% and 77% and 1-year overall survival of 90% and 91%; these outcomes were significantly better vs patients with ctDNA between 100 and 1,000 LG/mL and > 1,000 LG/mL, with a median progression-free survival of 3 months in both groups and median overall survival of 19 and 7.4 months, respectively.
Pretreatment ctDNA was significantly lower among patients developing no or grade 1 cytokine-release syndrome vs that among patients developing grade 2 or 3 cytokine-release syndrome with axicabtagene ciloleucel treatment (P = .0485). Pretreatment ctDNA was significantly lower among patients developing no or grade 1 immune effector cell–associated neurotoxicity syndrome (ICANS) vs that among those developing grade 2 to 4 ICANS (P = .0340).
At ctDNA assessment 1 week after axicabtagene ciloleucel infusion, ctDNA was undetectable in 23 (70%) of 33 patients with durable responses (no progression-free survival event with ≥ 6-month follow-up) vs 4 (13%) of 31 patients with disease progression (P < .0001).
For patients with detectable (n = 27) vs undetectable ctDNA (n = 34) at day 28, median progression-free survival was 3 months vs not reached (P < .0001) and median overall survival was 19 months vs not reached (P = .0080).
Among patients with radiographic partial response or stable disease on day 28, 1 (10%) of 10 patients with concurrently undetectable ctDNA experienced relapse compared with 15 (88%) of 17 patients with concurrently detectable ctDNA (P = .0001).
ctDNA was detected at or before radiographic relapse in 29 (94%) of 30 patients with relapse.
All patients with durable response had undetectable ctDNA at ≤ 3 months after axicabtagene ciloleucel infusion.
The investigators concluded, “Noninvasive ctDNA assessments can risk-stratify and predict outcomes of patients undergoing [axicabtagene ciloleucel] for the treatment of large B-cell lymphoma. These results provide a rationale for designing ctDNA-based risk-adaptive chimeric antigen receptor T-cell clinical trials.”
David B. Miklos, MD, PhD, of the Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
