S255: EFFICACY AND SAFETY OF TISAGENLECLEUCEL IN PEDIATRIC AND YOUNG ADULT PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) MATURE B-CELL NON-HODGKIN LYMPHOMA (NHL): THE PHASE II BIANCA STUDY

Background: Chimeric antigen receptor (CAR)-T cell therapy (tx) targeting CD19 is approved for treatment of adult r/r large B-cell lymphoma (LBCL) and pediatric r/r B-cell acute lymphoblastic leukemia (ALL). Pediatric and young adult pts with r/r mature B-NHL have dismal prognoses, especially those with Burkitt lymphoma (BL), and limited clinical benefit from available tx. Aims: Herein we report primary efficacy and safety outcomes from the global, multicenter, open-label, single-arm Phase II BIANCA trial (NCT03610724). Methods: Pts ≤25 y and ≥6 kg at screening with histologically confirmed CD19+ r/r mature B-NHL after ≥1 prior lines of tx were eligible following successful leukapheresis. Pts received optional bridging chemotherapy and fludarabine/cyclophosphamide or cytarabine/etoposide for lymphodepletion prior to a single intravenous injection of tisagenlecleucel (target dose range, 0.2-5x106/kg bodyweight [pts ≤50 kg] or 0.1-2.5x108 [pts >50 kg] CAR+ viable T cells). The primary endpoint was overall response rate (ORR=complete response [CR]+partial response [PR]) by local investigator assessment in the efficacy analysis set (EAS), which excludes pts with pre-infusion CR. Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, and CAR-T cell kinetics. Results: As of October 10, 2021, 33/34 pts enrolled received tisagenlecleucel (EAS, N=28). Median age was 13 y (range, 3-22 y), 70% were male, 55% had BL, and 45% had LBCL. Pts received a median of 2 prior tx (18% received prior stem cell transplant [SCT]), 85% had stage III/IV disease at initial diagnosis, 15% were primary refractory, 30% were refractory, and 55% had relapsed/progressed at study entry. Median time from enrollment to infusion was 35 d (range, 7-62 d). Median time from tisagenlecleucel infusion to data cutoff was 16 mo (range, 6-30 mo). Bridging chemotherapy was given to 94%. ORR was 32% (95% CI: 15.9-52.4); 7% had a CR. Subgroup analysis suggested that pts with BL had a lower ORR than pts with LBCL (20% vs 46%). Median PFS was 2.5 mo (95% CI: 1.1-2.9); median OS was 11.4 mo (95% CI: 3.4-not estimable); 12-mo estimated PFS and OS were 23% (95% CI: 8.9-40.3) and 47% (95% CI: 26.6-65.0), respectively. Of the 18 BL pts, 7 (39%) are alive post infusion (1 received allogeneic SCT, 1 surgery, 3 other tx, and 2 no other tx). There were no tx-related deaths; most tx-related grade (gr) ≥3 (94%) and serious (52%) adverse events occurred ≤8 w post infusion. A neurologic event (NE) occurred in 27%; 15% had a gr ≥3 NE, and none had gr 5 NE. Cytokine release syndrome (CRS; per Lee 2014 criteria) occurred in 70%, 9% had gr 3 CRS, and there was no gr ≥4 CRS. Median time to CRS onset and duration were 6 d (range, 1-27 d) and 5 d (range, 1-13 d), respectively. Only 1 pt died ≤30 d post infusion, due to disease progression. Geometric mean maximal expansion (Cmax) across all pts was 5730 copies/μg, and median time to Cmax was 12.8 d (range, 2.5-21.9 d) by qPCR. Median CAR-T cell persistence in pts with CR or PR was 182 d (range, 20.9-562 d). Image:Summary/Conclusion: Tisagenlecleucel demonstrated efficacy in pediatric and young adult pts with r/r mature B-NHL and comparable safety to that recorded in adults with DLBCL. The OS is encouraging; however, optimal positioning of tisagenlecleucel in the treatment of pediatric r/r B-NHL requires further exploration, especially for BL, which is highly aggressive and challenging to treat in the relapse setting.

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