KEY TAKEAWAYS
- The DESCAR-T observational study aimed to evaluate prognostic significance of histological subtypes in pts after anti-CD19-CAR T-cell therapy in pts with TriNHL vs LBCL.
- Reserachers noticed that comparatively higher efficacy was seen with tolerable AEs.
In the pivotal trials like ZUMA-1, JULIET, and TRANSCEND, anti-CD19 chimeric antigen receptor (CAR) T-cell therapies had demonstrated promising outcomes in heterogeneous histological groups as classified by the 5th edition of the WHO classification of haematolymphoid tumors. These groups included diffuse large B-cell lymphomas (DLBCL), high-grade B-cell lymphomas (HGBCL), and transformed indolent non-Hodgkin lymphomas (TriNHL).
Irrespective of the advancements, the specific impact of histological subtypes on treatment outcomes remains unclear, particularly whether TriNHL might exhibit a different prognostic profile compared to large B-cell lymphoma (LBCL).
Optimizing treatment strategies requires understanding these differences and predicting outcomes in patients (pts) undergoing CAR T-cell therapy.
Pierre SYu Zhengtephan and the team aimed to assess the prognostic value of TriNHL vs LBCL in the context of CAR T-cell therapy by using adapted propensity score matching (PSM) analysis.
Researchers studied a large cohort of pts with relapsed/refractory (R/R) aggressive B-cell lymphomas treated with commercial CAR T-cell products from July 1st, 2018, to September 1st, 2023, using data from the French DESCAR-T registry.
Diagnosis confirmation of transformation was conducted by expert pathological review (LYMPHOPATH) based on biopsies performed within 4 months before CAR T-cell infusion. To mitigate biases, they used PSM to create a balanced comparison with a cohort of biopsy-proven in pts with LBCL.
Covariates included age, sex, LDH level, CRP, Eastern Cooperative Oncology Group (ECOG), PS, Ann Arbor stage, prior treatment lines, bridging therapy, bulk at lymphodepletion, center, year of CAR T-cell decision, and CAR T-cell type. Application of 1:1 matching without replacement and optimal matching with a 0.1 propensity score caliper was done. Inverse probability weighting (IPW) was used to validate the findings, ensuring robust analysis of treatment outcomes and prognostic factors in this patient group.
They observed that in 503 pts, 112 had biopsy-proven TriNHL, and 391 had LBCL, with matching variables established before CAR T-cell infusion. All pts received treatment with commercial CAR T cells following at least 2 prior lines of therapy. In the 1:1 matched population (N=170, including 85 pts with TriNHL and 85 with LBCL, the median follow-up was 19.4 months (95% CI, 12.0-25.1) for TriNHL and 18.5 months (95% CI, 13.8-24.8) for LBCL.
The TriNHL group showed a contrastingly longer median progression-free survival (PFS) vs LBCL (18.3 months vs. 3.8 months), with a higher one-year PFS rate of 55.8% (95% CI, 43.6-66.4) vs 31.7% (95% CI, 21.4-42.6) for LBCL (HR = 0.54, 95% CI, 0.36-0.82, P=0.0034). Also, median overall survival (OS) was prolonged in the TriNHL group at 36.6 months, contrasting with 15 months in the LBCL group. The one-year OS rates were 72.1% (95% CI, 59.6-81.4) for TriNHL versus 50.7% (95% CI, 38.2-62.0) for LBCL (P=0.031).
The TriNHL group exhibited superior OS rates and complete response rates (CRR) at 82.4% and 63.5%, in the same order, 63.5% and 50.6% in the LBCL group. These results were consistent when using the inverse probability weighting (IPW) statistical approach.
In terms of adverse events (AEs), cytokine release syndrome (CRS) of any grade occurred in 78.8% of TriNHL pts, with 2.4% experiencing grade 3 or higher, while in the LBCL group, CRS occurred in 83.5% of pts, with 4.7% having grade 3 or higher. Neurotoxicity of any grade occurred in 29.4% of TriNHL pts, with 5.9% having grade 3 or higher, compared to 32.9% and 4.7%, respectively, in the LBCL group.
The study concluded a matched comparison between pts with TriNHL and LBCL, revealing higher efficacy with tolerable toxicity profiles in the former group.
The trial was sponsored by Lymphoma Academic Research Organisation.
Source: https://library.ehaweb.org/eha/2024/eha2024-congress/422345
Clinical Trial: https://wstudyww.clinicaltrials.gov/study/NCT04328298
Stephan P, Blasi R D, Roulin L, (2024). “TRANSCAR: a real-life outcome study of relapsed/refractory transformed indolent non-Hodgkin lymphoma in the context of CAR T-cells a DESCART analysis.” Presented at EHA 2024. (abstr 422345; S241), https://library.ehaweb.org/eha/2024/eha2024-congress/422345
