EARLY CTDNA CLEARANCE AFTER CAR T‐CELL INFUSION PREDICTS OUTCOME IN PATIENTS WITH LARGE B‐CELL LYMPHOMA : RESULTS FROM ALYCANTE, A PHASE 2 LYSA STUDY

Abstract

Introduction: CAR T-cells have significantly improved the outcome of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). However, more than half of the patients fail to obtain a prolonged remission, resulting in a poor prognosis. Early identification of these patients would allow early intervention to improve their outcome. Circulating tumor DNA (ctDNA) assessment is a promising tool to monitor early response in LBCL, but few data are available regarding ctDNA monitoring after treatment with CAR T-cells. The aim of our study was to monitor ctDNA before and after CAR T-cell infusion and correlate the results with clinical outcome in the ALYCANTE trial. Methods: Patients’ samples were prospectively collected in the ALYCANTE trial, an open-label, phase 2 study (NCT04531046), designed to evaluate the efficacy and safety of axi-cel in 62 patients with R/R LBCL not intended for autologous stem cell transplantation after 1 prior line of therapy. DNA was extracted from 2 to 4 mL of plasma. Libraries were generated from 129 kb captured-DNA custom panel (Agilent, XTHS2). Variant calling and phased variant annotation were performed using Unique Molecular Identifiers (UMI). Concentrations of ctDNA were expressed as hGE/mL and were measured at leukapheresis, after bridging/before lymphodepletion, at time of CAR T-cell infusion (D0) and at day 14 (D14), month 1 (M1), 3, 6, 9, and 12 after infusion. These results were correlated with clinical outcome. Results: With a median of 85 variants (range 1–707), a mutational profile could be identified from ctDNA in 88% (55/62) of patients at time of leukapheresis (n = 54) or after bridging (n = 1). The median ctDNA load was 77 hGE/mL (range 0–6803) at leukapheresis and 39 hGE/mL (range 2–17,354) after bridging therapy. Only 2/55 (4%) patients experienced ctDNA clearance after bridging. To date, we report the clinicobiological correlations for the first 40 patients included in the ALYCANTE trial. Early ctDNA evaluation was performed in 38/40 (95%) patients: at D14 and M1 (n = 34), at D14 only (n = 2), or at M1 only (n = 2). For patients with D14 and M1 evaluation, the results were concordant in 32/34 (94%) patients, either both positive (n = 19) or both negative (n = 13). A negative ctDNA at D14 (n = 14/36, 38.9%) or at M1 (n = 16/36, 44.4%) was associated with a complete metabolic response at 3 months in 93% (p = 0.03) and 94% (p = 0.009) of cases, respectively. After a median follow-up of 10 months, the median progression-free survival was not reached in patients with negative ctDNA at D14 and M1 versus 7.6 months and 5.8 months for patients with positive ctDNA at D14 and M1, respectively (Figure 1). Encore Abstract—previously submitted to EHA 2023 The research was funded by: Kite-Gilead, as a prespecified exploratory analysis Keywords: cellular therapies, liquid biopsy, minimal residual disease Conflicts of interests pertinent to the abstract M. Delfau-Larue Other remuneration: Education, symposia: TAKEDA, AMGEN, ROCHE, GILEAD, ABBVIE G. Cartron Consultant or advisory role: Advisory Board: Ownards Therapeutics, MAbQi. Consultancy: Roche, BMS, Abbvie. Honoraria: Jansen, Gilead, Takeda, Novartis, Milteny. F. Morschhauser Consultant or advisory role: Roche, Gilead, Genmab, Novartis, Abbvie Honoraria: Chugai (scientific lectures) L. Oberic Consultant or advisory role: Roche, Kite Gilead, Incyte Honoraria: Speaking: Roche, Kite Gilead, AstraZeneca, Jansen, BMS E. Bachy Consultant or advisory role: Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer; Honoraria: Kite, a Gilead Company, Bristol Myers Squibb, Novartis, Pfizer, Incyte, ADC Therapeutics Research funding: Amgen, BMS R. Dulery Honoraria: Takeda, Novartis, and Biotest C. Laurent Educational grants: Janssen R. Houot Consultant or advisory role: Kite/Gilead, Novartis, Bristol-Myers Squibb/Celgene, ADC Therapeutics, Incyte and Miltenyi. Honoraria: Kite/Gilead, Novartis, Incyte, Janssen, MSD, Takeda and Roche