| Abstract: |
Double-hit (DHL) and double expressor (DEL) DLBCL have poor prognosis with standard therapy but CART may overcome this poor prognostic impact. In this multicenter retrospective study, we sought to confirm this observation by evaluating survival outcomes among patients with relapsed/refractory DHL and DEL treated with CART and evaluate outcomes of relapse post-CART. A total of 408 adult patients with relapsed/refractory DLBCL from 13 academic centers were included based on the availability of DHL and DEL. All 408 patients were included in the DHL (n = 80) vs non-DHL (n = 328) analysis, while 333 patients were included in the analysis of DHL (n = 80) vs DEL (n = 74) vs non (n = 179). On MVA, there were no differences for PFS for DHL vs non-DHL (HR 0.8, 95%CI 0.5–1.3, p = 0.35) or DHL vs DEL vs other (three-way p value, p = 0.5). Response rates and toxicities were similar among groups. Patients with DEL had the highest relapse rates post-CART, while DHL had the worst overall survival after CART relapse. In sum, our data support the notion that CART cell therapy can overcome the poor prognostic impact of DHL and DEL DLBCL in the relapsed/refractory setting. Additionally, patients with DHL that relapse after CART have a very poor prognosis. © The Author(s) 2025. |
| Keywords: |
immunohistochemistry; adult; cancer survival; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; retrospective studies; young adult; human cell; major clinical study; overall survival; lenalidomide; clinical trial; mortality; cancer recurrence; cancer combination chemotherapy; recurrence risk; follow up; protein bcl 2; progression free survival; cohort analysis; retrospective study; cause of death; germinal center; immunology; tumor burden; multicenter study; lactate dehydrogenase; protein bcl 6; lymphoma, large b-cell, diffuse; follicular lymphoma; disease exacerbation; therapy; adoptive immunotherapy; immunotherapy, adoptive; cd19 antigen; antigens, cd19; autologous hematopoietic stem cell transplantation; adverse event; clinical outcome; infusion rate; second-line treatment; cytokine release syndrome; diffuse large b cell lymphoma; refractory cancer; ibrutinib; very elderly; humans; prognosis; human; male; female; article; transformed follicular lymphoma; tisagenlecleucel t; double-expressor lymphoma; double-hit lymphoma; knowledge gap; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; lisocabtagene maraleucel; tafasitamab; cd19 molecule, human; bridging therapy; tisa cel; liso cel
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