CD19.CAR T Cells(University Hospital Heidelberg)

We retrospectively evaluated the treatment outcomes of 47 adult patients with TP53‐mutated acute lymphoblastic leukaemia (ALL) treated with either blinatumomab, inotuzumab or/and CD19 CAR T‐cell therapy. The complete remission with or without count recovery (CR/CRi) (negative minimal residual disease (MRD−) rate) following treatment with blinatumomab (n = 46), inotuzumab (n = 26) and CD19 CAR T cells (n = 6) was 58.7% (96.3%), 61.5% (60%) and 66.7% (75%) respectively. The median OS was 13.6 months (95% CI: 9.6–17.2) for all patients, and it was not significantly different based on the individual novel salvage therapy (p = 0.40). The 12‐month leukaemia‐free survival (LFS) for responders to blinatumomab, InO and CAR T cells was 20%, 11% and 0% (p = 0.743) respectively. Patients who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) post‐response had improved 12‐month LFS compared to those who did not (35% vs. 9%, p = 0.014). Among relapsed patients following blinatumomab, 11 (61%) presented with CD19‐negative disease. Hence, targeted and immune‐based therapies are effective in inducing high MRD‐negative remission rates in adults with B‐cell ALL harbouring TP53 mutations. Nonetheless, the durability of remission is short in the absence of allogeneic HCT consolidation and relapse frequently manifested as CD19‐negative disease following blinatumomab.

Richter transformation (RT) is a serious complication of chronic lymphocytic leukaemia (CLL), with poor outcomes. While CAR T‐cells have shown promise in large B‐cell lymphoma, their efficacy in RT remains unclear, and the role of allogeneic stem cell transplant (alloSCT) post‐CAR T‐cells has not been established. This study aimed to assess the clinical response and survival of patients with RT treated with anti‐CD19 CAR T‐cells. This retrospective multicentre study, conducted by the European Research Initiative on CLL (ERIC), included patients with RT who received anti‐CD19 CAR T‐cells between 06/2018 and 01/2024. Progression‐free survival (PFS) and overall survival (OS) were evaluated from CAR T‐cell infusion. Fifty‐four patients with RT were treated with anti‐CD19 CAR T‐cells (academic products, n  = 29; commercial products, n  = 25). The median age was 63 years, with 72% having an ECOG performance status (PS) of 0 to 1. Seven patients (13%) underwent alloSCT following CAR T‐cell infusion, with the indications being consolidation therapy ( n  = 4) and relapse/progression ( n  = 3). The overall response rate was 65%, with 46% achieving complete response (CR) at 1 month and 50% at 3 months. The median PFS was 8.0 months (95% CI: 2.1–13.8) and the median OS was 14.4 months (95% CI: 8.8–19.2). The median PFS was 31.6 months for patients achieving CR at 1 or 3 months post CAR T‐cells. Significant factors associated with mortality included high ECOG PS ( p  < 0.001), high LDH at CAR T infusion ( p  = 0.005), ICANS ( p  = 0.046) and no response at 1 month ( p  = 0.02). Multivariable Cox regression analysis identified treatment response at 1 month ( p  = 0.001) and increasing age ( p  = 0.5) as significant predictors of mortality. This study shows encouraging response rates and manageable toxicity for patients with RT treated with both academic and commercially available CAR T‐cell products.