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Aim: The aim of this study was to analyse the outcomes of patients with large B‐cell lymphoma (LBCL) treated with chimeric antigen receptor T‐cell therapy (CAR‐Tx), with a focus on outcomes after CAR T‐cell failure, and to define the risk factors for rapid progression and further treatment. Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd‐line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022. Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression‐free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty‐three patients (59%) were refractory or relapsed after CAR‐Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow‐up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR‐Tx. Risk factors for not receiving further therapy after CAR‐Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS‐2 (from R/P after CAR‐Tx) was 6.7 months (6‐month 57.9%) for treated patients and 0.4 months (6‐month 4.2%) for untreated patients (p < 0.001). The median PFS‐2 (from R/P after CAR‐Tx) was 3.2 months (6‐month 28.5%) for treated patients. The risk factors for a shorter PFS‐2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS‐2 for treated patients. Conclusion: Our findings allow better stratification of CAR‐Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement). [ABSTRACT FROM AUTHOR]

This contrasts with reports of CD19 expression loss after bispecific anti-CD19 treatment and CD19-directed CAR T-cell treatments [[7]]. CD19 is an important target for novel anti-lymphoma treatments as it is broadly and homogenously expressed across many B-cell malignancies [[1]]. DNA and RNA analyses did not find evidence for CD19 mutations, dominant exon skipping or loss of CD19 mRNA expression, which would be indicative of resistance to further CD19-targeted therapy. [Extracted from the article]

We analyzed 495 MCL patients from the Czech Lymphoma Study Group data registry. With the median follow-up of 4.4 years, 51.7% patients progressed or relapsed and 34.1% died. Five-year overall survival reached 65.3% and five-year progression free survival 44.1% of the patients. Maintenance rituximab (MR) after first line therapy improved overall and progression free survival compared to the patients under observation only (both p <.001). Elevated beta-2-microglobulin (p =.003), presence of systemic symptoms (p =.002), ECOG >0 (p =.003), age (p =.014), and MIPI (p <.001) were associated with MR failure. Patients who did not achieve complete remission have had two-fold higher risk of MR failure (p <.001). Autologous stem cell transplant reduced the risk of MR failure by 69% (p <.001). The MIPI and the beta-2-microglobulin were identified as independent predictors of MR failure (p =.02 and p =.03, respectively). Patients who relapsed/progressed on MR reached shorter OS calculated from the MR start compared to patients without failure (HR = 15.0; p <.001). [ABSTRACT FROM AUTHOR]