Background: Varnimcabtagene autoleucel, a CD19 directed CAR-T cell therapy with a 4-1BB co-stimulatory domain and a non-FMC63 based murine scFv (A3B1 binder), has demonstrated remarkable responses in relapsed/refractory B cell malignancies (RR BCM) in the IMAGINE study. Reinfusion of var-cel is an option to improve functional persistence for CD19+ relapsed disease. This abstract describes the clinical outcomes following reinfusion of var-cel in patients (pts) who relapsed after first infusion. Methods: Patients (pts) aged 3 to 45 years (B-ALL) and ≥ 18 years (B-NHL) with RR BCM were eligible for IMAGINE study if they had measurable disease, as assessed by lymphoid blasts (B-ALL) or metabolic tumour bulk (B-NHL), received ≥1 prior regimen, refractory to the last line of treatment with good performance status (ECOG 0 to 1). The primary target dose was 1x10 6/kg CAR+ cells (B-ALL) and 5x10 6/kg CAR+ cells (B-NHL) (overall range 0.1x10 6 to 5x10 6) and was infused over 3 days (10%/30%/60% fractions). Primary objectives were overall response rate (ORR: CR + CRi in B-ALL and CR + PR in B-NHL) at day +90 after first infusion, and safety. Response was assessed as per NCCN (B-ALL) and IWG (B-NHL) criteria. Adverse events (AEs) were graded using CTCAE v5.0. CRS and ICANS were graded according to ASTCT criteria. Criteria for reinfusion was: 1) achieved response with subsequent disease progression and presence of CD19 positive malignant cells; 2) available second dose for retreatment from initial apheresis and manufacturing run; and 3) after primary endpoint at D+90. This abstract evaluates the outcomes at D+28 after var-cel reinfusion. Results: At data cut-off, 25 pts were enrolled (median age 31 yrs, range 3 - 66) with RR BCM (n=13 B-ALL; n=12 B-NHL). 24 pts received var-cel (1 withdrawal) with majority of infusions on Days 0, +3, +7. ORR was 91.7% at D+28 and 80.9% at D+90. Median progression free survival (PFS, range 12-NR), duration of response (DOR, range 0-NR) and overall survival (OS) were not reached (range 12-NR). Nine pts had relapsed disease (37.5%) with median PFS of 178 days (range 28-319). Of these 9 pts, 7 had CD19+ relapse (77.8%) and 2 (with B-ALL) had CD19- relapse. Four of these pts received second infusion at full dose (same as primary infusion) fractionated over 3 days (10%, 30%, 60%). For these 4 pts, duration of B cell aplasia after primary infusion was 90 days to NR (range); var-cel was detectable in 1 pt (n=1/4) at relapse; and median PFS was 166 days (range 90-275). Tumour burden at relapse was: Ph+ B-ALL (n=1) with 22% blasts (p210 BCR ABL transcript 36.7%); B-NHL (n=3) with TMTV range 7.5 to 277 ml and SPD range 660.5 to 8686 mm 2 (Table 1). PDL1 exhaustion marker was expressed in one B-NHL pt only. Salvage regimen in B-NHL pts was involved field radiotherapy (n=2); 1 B-NHL pt was reinfused without salvage treatment. B-ALL pt received Dasatinib, Inotuzumab and CNS prophylaxis. Preparative conditioning regimen for these 4 patients were: Fludarabine-Cyclophosphamide (n=1), with Rituximab (n=2) and Rituximab with Nivolumab (n=1). Post reinfusion, var-cel was not detected in 1 pt (B-ALL) however B cell aplasia was persistent. In B-NHL pts, Cmax range was 7222 to 31846 CAR+ copies / ug genomicDNA; Tmax was D+2 after reinfusion and duration of var-cel persistence was range 2 days to NR (Figure 1). Post reinfusion, no CRS (0%) or ICANS (0%) was reported. Hematotoxicity was the most common AE (100%) with neutropenia (G3+ 100%); anemia (G3+ 66.7%); and thrombocytopenia (G3+ 33.3%;). Hypogammaglobulinemia (IgG <4g/L) was seen in 2 pts (50%, new onset 1 pt). Time to first response after reinfusion was 28 days. The D+28 ORR for evaluable pts (n=2) was 100%. Median PFS after reinfusion is NR. Post reinfusion 1 pt (Ph+ B-ALL) died of disease progression at 313 days (50 days after reinfusion). The evaluable B-NHL pts are in remission. Conclusions: Reinfusion of varnimcabtagene autoleucel (IMN-003A) is feasible, safe and well tolerated. Preparative conditioning regimen for reinfusion needs personalization guided by CAR persistence, disease biology (CD20, PDL1 expression) and haematological reserve. After reinfusion, prolonged B cell aplasia was observed with 100% ORR at D+28 in evaluable pts. Var-cel was detected post reinfusion in B-NHL patients with sustained responses. Reinfusion may be considered in preference for some pts. The ideal preparative regimen and pt characteristics to guide reinfusion outcomes remains an area of research.