Circulating Tumor DNA Assessment of Disease Response in Large B-Cell Lymphoma: Lisocabtagene Maraleucel Versus Autologous Stem Cell Transplantation Standard Therapy
Menée à partir d'échantillons plasmatiques prélevés sur 136 patients atteints d'un lymphome à grandes cellules B et ayant reçu un traitement par lisocabtagène maraleucel ou un traitement standard par greffe autologue de cellules souches, cette étude évalue l'association entre le niveau de maladie résiduelle mesuré à l'aide de l'ADN tumoral circulant et la réponse thérapeutique ou le pronostic
We report correlative circulating tumor DNA (ctDNA) analyses from TRANSFORM (ClinicalTrials.gov identifier: NCT03575351) evaluating lisocabtagene maraleucel (liso-cel) versus standard of care (salvage immunochemotherapy, high-dose chemotherapy, autologous stem cell transplantation [ASCT]) in second-line large B-cell lymphoma (LBCL). ctDNA association with efficacy was investigated at predefined time points (random assignment, day 43, day 64, and day 126 [3 months after liso-cel, approximately 2 months after ASCT]) for 136 patients using ultrasensitive PhasED-Seq. ctDNA clearance (measurable residual disease [MRD]neg) predicted longer event-free survival (EFS) at all time points in both arms, with significantly more liso-cel–treated patients achieving MRDneg. Liso-cel demonstrated superior outcomes versus ASCT, including longer EFS, progression-free survival (PFS), and duration of response among patients in complete response (CR) and MRDneg. ctDNA re-emergence in patients with CR after ASCT confirmed its potential in predicting relapse. MRDneg remained significantly associated with EFS after adjusting for positron emission tomography (PET) response, while interaction testing revealed a significant interaction between PET status and treatment arm for EFS. Liso-cel achieved deeper, more durable molecular clearance by ctDNA, consistent with superior EFS and PFS versus ASCT for second-line LBCL treatment. ctDNA-MRD provided prognostic value beyond PET, supporting its role as a complementary biomarker for treatment response and relapse prediction.
Journal of Clinical Oncology , article en libre accès, 2026