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AbstractPrognostic assessment in chronic lymphocytic leukemia (CLL) is essential for delivery of timely, personalized therapy. TP53 status, karyotype, IGHV mutational status, minimal residual disease (MRD), gene mutations and markers of cell proliferation were important prognostic tools in the era of chemo-immunotherapy (CIT). With BCL2 inhibitors (BCL2i), outcome is still impacted by IGHV status, TP53 status, complex karyotype, and achievement of undetectable MRD. On the other hand, BTK inhibitors (BTKi) are agnostic to IGHV status, rarely cause MRD negative remissions and are less clearly impacted by TP53 status. Although based on less mature data, outcomes with BCL2i/BTKi combinations are likely influenced by TP53 and IGHV status. Responses to non-covalent BTKI (ncBTKI) are impacted by the mechanism of resistance to previous covalent BTKi. Finally, responses to chimeric antigen receptor T cell therapy (CAR-T) appear independent of TP53 status, but dependent on overall T- cell fitness. [ABSTRACT FROM AUTHOR]

Background: Double‐expressor lymphoma (DEL) has a poorer prognosis than other subtypes of diffuse large B‐cell lymphoma (DLBCL). This study is a multicenter, prospective, single‐arm, phase 2 clinical study initiated by investigators to evaluate the efficacy and safety of combined zanubrutinib with R‐CHOP, which includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone for patients with DEL (stage II or more), as well as to explore factors related to efficacy preliminarily. Methods: From November 2020 to July 2022, 48 newly diagnosed patients were enrolled. All patients received twice‐daily oral zanubrutinib (160 mg) for 6 months and standardized R‐CHOP regimen for six to eight cycles. Results: The objective response rate (ORR) was 89.6%, with a complete response rate (CRR) of 83.3%. The median follow‐up was 29.3 months. The median progression‐free survival (PFS) and overall survival (OS) were not reached. The PFS and OS were 81.25% and 93.75% at 2 years, respectively. Grade ≥3 adverse events (AEs) were reported in 23 of 48 (47.9%) patients. Next‐generation sequencing (NGS) results of 33 patients showed that TP53, MYD88, and PIM1 were the most common mutated gene. Multivariate analysis revealed that BCL‐6 gene rearrangement was an adverse prognostic factor for both PFS (hazard ratio [HR], 0.247; 95% confidence article [CI], 0.068–0.9; p =.034) and OS (HR, 0.057; 95% CI, 0.006–0.591; p =.016), whereas the number of extranodal involvements also significantly influenced OS (HR, 15.12; 95% CI, 1.07–213.65; p =.044). Conclusions: Zanubrutinib in combination with R‐CHOP is an effective option for DEL patients, and the toxicity of zanubrutinib is entirely acceptable for patients. [ABSTRACT FROM AUTHOR]