Dean, Erin A.;
Kimmel, Gregory J.;
Frank, Matthew J.;
Bukhari, Ali;
Hossain, Nasheed M.;
Jain, Michael D.;
Dahiya, Saurabh;
Miklos, David B.;
Altrock, Philipp M.;
Locke, Frederick L.
Circulating tumor DNA adds specificity to PET after axicabtagene ciloleucel in large B-cell lymphoma
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Media type:
E-Article
Title:
Circulating tumor DNA adds specificity to PET after axicabtagene ciloleucel in large B-cell lymphoma
Contributor:
Dean, Erin A.;
Kimmel, Gregory J.;
Frank, Matthew J.;
Bukhari, Ali;
Hossain, Nasheed M.;
Jain, Michael D.;
Dahiya, Saurabh;
Miklos, David B.;
Altrock, Philipp M.;
Locke, Frederick L.
imprint:
American Society of Hematology, 2023
Published in:Blood Advances
Language:
English
DOI:
10.1182/bloodadvances.2022009426
ISSN:
2473-9529;
2473-9537
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title>
<jats:p>We examined the meaning of metabolically active lesions on 1-month restaging nuclear imaging of patients with relapsed/refractory large B-cell lymphoma receiving axicabtagene ciloleucel (axi-cel) by assessing the relationship between total metabolic tumor volume (MTV) on positron emission tomography (PET) scans and circulating tumor DNA (ctDNA) in the plasma. In this prospective multicenter sample collection study, MTV was retrospectively calculated via commercial software at baseline, 1, and 3 months after chimeric antigen receptor (CAR) T-cell therapy; ctDNA was available before and after axi-cel administration. Spearman correlation coefficient (rs) was used to study the relationship between the variables, and a mathematical model was constructed to describe tumor dynamics 1 month after CAR T-cell therapy. The median time between baseline scan and axi-cel infusion was 33 days (range, 1-137 days) for all 57 patients. For 41 of the patients with imaging within 33 days of axi-cel or imaging before that time but no bridging therapy, the correlation at baseline became stronger (rs, 0.61; P &lt; .0001) compared with all patients (rs, 0.38; P = .004). Excluding patients in complete remission with no measurable residual disease, ctDNA and MTV at 1 month did not correlate (rs, 0.28; P = .11) but correlated at 3 months (rs, 0.79; P = .0007). Modeling of tumor dynamics, which incorporated ctDNA and inflammation as part of MTV, recapitulated the outcomes of patients with positive radiologic 1-month scans. Our results suggested that nonprogressing hypermetabolic lesions on 1-month PET represent ongoing treatment responses, and their composition may be elucidated by concurrently examining the ctDNA.</jats:p>