Zanubrutinib Combined with R-CHOP As the First-Line Treatment for Newly Diagnosed Diffuse Large B-Cell Lymphoma with Extranodal Involvement: A Prospective Phase II Trial in China

BACKGROUND

About one-third of Diffuse large B-cell lymphoma (DLBCL) arises primarily from extranodal sites, patients with extranodal involvement indicates poor clinical outcomes.There is an urgent need to find new treatments for DLBCL patients with extranodal involvement.

METHODS

We conducted a single-arm, prospective phase II trial for newly diagnosed DLBCL with extranodal involvement to evaluate the efficacy and safety of the zanubrutinib combined with R-CHOP. Patients received therapies: R-CHOP intravenously Rituximab (375mg/m2 on Day0), Cyclophosphamide (750mg/m2on Day1), Doxorubicin (50mg/m2 on Day1), Vincristine(1.4mg/m2 on Day1), and oral Prednisone(50mg/day Day1-5) with Zanubrutinib (160mg bid Day1-21) regimen.This trail was registered at Chinese Clinical Trial Registry(ChiCTR2100053056).

RESULTS

31 patients received ZR-CHOP regimen treatments at least 2 cycles, 26 patients completed 6 cycles. Patients had a median age of 68 years(38-79). 18 patients (58%) had intermediate and high risk of IPI score, 20 patients (65%) had stage III~IV disease, 22 patients (71%) were Non-GCB types, 19 patients (61%) Ki-67 More than 80%. 7 patients (23%) were double-expression lymphoma，5 patients (16%) with positive CD5 and 4 patients (13%) TP53 more than 80%. The objective response rate(ORR) was 96%(26/27), 12 patients(44%) reached complete remission(CR). 1 patient(3%) died for progression disease(PD) and 4 patients(13%) withdrew the trial. The most common adverse events of hematological toxicity were neutropenia, thrombocytopenia and anemia with 19%，13% and 10% grade 3/4 AEs respectively. The most common non-hematological toxicity were pneumonia, nausea and fatigue with 16%，6% and 3% grade 3/4 AEs .

CONCLUSIONS

Our results showed that Zanubrutinib plus R-CHOP(ZR-CHOP) is a safe and effective scheme for DLBCL patients with extranodal involvement. It indicate that the addition of zanubrutinib to the standard first-line treatment can enable these patients to achieve remission in the early stage of treatment and without significantly increasing toxicity.