Breaking diagnostic and therapeutic barriers in intravascular large B-cell lymphoma: A 13-year real-world study from China.

[BACKGROUND] Intravascular large B-cell lymphoma (IVLBCL) is an ultra-orphan disease (incidence 0.095/million/year) with dismal prognosis due to delayed diagnosis and limited therapeutic options. We aimed to evaluate a novel diagnostic algorithm and the efficacy of zanubrutinib-containing therapy in a real-world Chinese cohort.

[METHODS] This single-center retrospective study enrolled 54 IVLBCL patients (2010–2022). Diagnostic approaches evolved from PET/CT-guided biopsy to a combination of serum interleukin-10 (IL-10, cut-off 95.65 pg/mL), random skin biopsy (RSB), and circulating tumor DNA (ctDNA) profiling. Treatment regimens shifted from R-CHOP to methotrexate-based therapy (MTX), then to zanubrutinib plus R-CHOP (ZR-CHOP).

[RESULTS] The cohort exhibited distinct features: 35.2% Asian-variant IVLBCL, 50% CNS involvement, and 22.9% PET/CT negativity. IL-10 combined with RSB enabled the diagnosis of 11 PET/CT-negative patients who would have otherwise remained undiagnosed. ctDNA revealed (11/17, 65%) and (7/17, 41%) variants. ZR-CHOP ( = 22) achieved significantly superior 2-year progression-free survival (PFS) compared to R-CHOP alone ( = 6) (90% vs. 30%; hazard ratio [HR] 0.031,  < 0.0001) and demonstrated 100% central nervous system (CNS) relapse-free survival. The efficacy of ZR-CHOP was comparable to that of methotrexate (MTX)-based therapy ( = 20; 2-year PFS 85%), despite a shorter median follow-up (20.1 vs. 38.0 months).

[CONCLUSIONS] In this largest Asian IVLBCL cohort to date, IL-10 + RSB + ctDNA significantly improved diagnostic accuracy. Zanubrutinib demonstrated promising efficacy, particularly in CNS involvement, offering a pragmatic solution for this orphan disease.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s13023-026-04226-4.