The Interim Analysis from a Prospective Single-Center Phase 2 Study of Zanubrutinib Plus R-CHOP in Treat-Naïve Intravascular Large B Cell Lymphoma

Background: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease for which there is no available standard treatment. Zanubrutinib is a selective Bruton Tyrosine kinase(BTK) inhibitor and has shown activity in several B cell lymphomas. We aimed to ascertain the safety and activity of zanubrutinib plus R-CHOP (rituximab, cyclophosphamide, epirubicin, vindesine, and prednisolone) for patients with previously untreated IVLBCL

Methods: This is a prospective, single-arm, phase 2 trial at Peking Union Medical College Hospital in China. Eligible patients had untreated histologically confirmed IVLBCL, were aged>18 years, had adequate bone marrow and organ function, had no active infections or bleeding. Patients received 8 cycles of zanubrutinib (160mg bid orally) plus R-CHOP (rituximab 375 mg/m² intravenously on day 1; cyclophosphamide 750 mg/m², epirubicin 70 mg/m², and vindesine 4mg intravenously on day 1 and prednisolone 100 mg orally on days 1-5) every 3 weeks. The primary endpoint was 2-year progression-free survival. Secondary end points included safety profile. The trial is registered at ClinicalTrials.gov (NCT 04899570) and is still recruiting.

Results: By 15 ^th July,2021, 9 patients were enrolled into the study, 5 patients had finished 8 cycles treatment and 4 were still under treatment. All 9 patients were Ann Arbor IVB stage (median age 58, 5 males), and in intermediate-high/high risk group (IPI 3-5). 8 patients had the interim and/or end of treatment evaluation and in the efficacy population. All of them achieved response (overall response rate 100%), and the 5 patients who finished treatment achieved complete remission. 5 patients who had central nerves system involvement all got significant improvement in symptoms and MRI scans. Median follow-up was 10.0 months (range 1-18), no relapsing occurred and 1 patient died of septic shock 3 months after the completion of treatment. Every patient was enrolled into the safety population. The most common adverse effect (AE) were hematological toxicities, including Grade 3-4 neutropenia (6/9), Grade 3 anemia (2/9) and Grade 3-4 thrombocytopenia (2/9); all the hematological AE were mainly occurred in the first cycle. Any grade non-hematological toxicities included: fatigue(6/9)，infection(6/9)，infusion action(5/9)，anorexia(5/9), vomiting(5/9)，hypertention(1/9). There was no dose modification due to AE.

Conclusion: Zanubrutinib plus R-CHOP demonstrated promising efficacy as front-line regimen in IVLBCL, even in the CNS involvement patients. This regimen is well tolerated and it warrants future investigation in larger scale population and long-term follow-up.