Furstenau, Moritz 
ORCID: 0000-0002-6593-0140, Weiss, Jonathan, Giza, Adam, Franzen, Fabian, Robrecht, Sandra, Fink, Anna-Maria, Fischer, Kirsten, Schneider, Christof, Tausch, Eugen, Stilgenbauer, Stephan, Ritgen, Matthias, Schilhabel, Anke, Brueggemann, Monika, Eichhorst, Barbara, Hallek, Michael and Cramer, Paula ORCID: 0000-0003-4046-9922
(2022).
Circulating Tumor DNA-Based MRD Assessment in Patients with CLL Treated with Obinutuzumab, Acalabrutinib, and Venetoclax.
Clin. Cancer Res., 28 (19).
S. 4203 - 4212.
PHILADELPHIA:
AMER ASSOC CANCER RESEARCH.
ISSN 1557-3265
Abstract
Purpose: With the advent of highly efficacious time-limited combination treatments of targeted agents in chronic lympho-cytic leukemia (CLL), minimal residual disease (MRD) assess-ment has gained importance as a measure for therapeutic success and as a surrogate for progression-free survival. The currently most widely used method is multicolor flow cytometry, which detects circulating CLL cells in the peripheral blood. However, it seems to be less sensitive for the detection of MRD in the lymph node compartment. Patients and Methods: To evaluate whether a cell-free approach can overcome this limitation, we performed serial assess-ments of circulating tumor DNA (ctDNA) in patients with CLL treated with obinutuzumab, acalabrutinib, and veneto-clax in the phase II CLL2-BAAG trial. Patient-specific vari-ability, diversity, joining (VDJ) rearrangements as well as somatic driver mutations were tracked before, during and after treatment by digital droplet PCR in blood plasma. Furthermore, these were systematically compared to matched flow cytometry data.Results: In the 381 sample pairs, ctDNA and flow cytometry yielded highly concordant results. However, clone-specific ctDNA was detected in 44 of 152 samples (29%) that were assessed as undetectable MRD (uMRD) by flow cytometry (defined as less than one CLL cell in 10,000 normal leukocytes). 29 ctDNA-negative samples showed detectable MRD >10-4 by flow cytometry. Also, somatic driver mutations were detected with a similar sensitivity compared with patient-specific VDJ rearrangements in plasma. In patients with predominantly nodal residual disease, ctDNA com-pared favorably with 4-color flow cytometry and seemed to more accurately reflect the entire disease burden across compartments. Conclusions: On the basis of these findings, ctDNA-based MRD assessment appears to be a promising method to comple-ment cell-based MRD approaches like flow cytometry that focus on circulating CLL cells in the peripheral blood.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-677201 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.1158/1078-0432.CCR-22-0433 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Clin. Cancer Res. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 28 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Number: | 19 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Page Range: | S. 4203 - 4212 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date: | 2022 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | AMER ASSOC CANCER RESEARCH | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | PHILADELPHIA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 1557-3265 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/67720 |
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