ZR-CHOP Shows Promise in Treatment-Naïve DLBCL

Lymphomas: © David A Litman - stock.adobe.com

The combination of zanubrutinib (Brukinsa), rituximab (Rituxan), cyclophosphamide, hydroxydaunomycin, vincristine sulfate (Oncovin), and prednisone (ZR-CHOP) was observed to be safe and effective in the treatment of patients with treatment-naïve non-germinal center B-cell (GCB) diffuse large B-cell lymphoma (DLBCL) with extranodal involvement, according to findings published in Frontiers in Immunology.¹

With a median follow-up of 16.7 months (range, 1.7-28.2 months), the 1-year progression-free survival (PFS) was 80.8%, and 1-year overall survival was 88.5% with ZR-CHOP. The expected PFS for 2 years is 74.0%, and OS is 88.5%. The overall response rate (ORR) was 91.3%, with a complete response (CR) rate of 82.61%, and partial response rate of, 8.70%). The median duration of response (DoR) was 13.5 months (range, 3.2-25.1 months).

“Although the overall sample size may not be enough, we still observe a good benefit trend in these patients,” study authors wrote.

The prospective, single-arm, single-center, phase 2 clinical trial (NCT04835870) investigated the efficacy and safety of zanubrutinib combined with R-CHOP in patients with newly diagnosed non-GCB DLBCL with extra nodal involvement.² The primary end point was PFS in the intent-to-treat population based on Lugano 2014 criteria. The secondary end points were ORR, CR, and DoR based on Lugano 2014 criteria, as well as safety and tolerability.

The study had an enrollment of 26 patients between October 2020 and March 2022, and 23 patients could be evaluated for efficacy. Two patients died from causes outside of disease progression; 1 patient died suddenly, and another died from a hereditary cerebral hemorrhage. One patient withdrew from the study voluntarily after 2 treatment cycles. Patients were aged between 31 and 83 years, and the median age was 62 years.¹

For safety, hematological adverse events (AEs) with severity grade 3 or higher included neutropenia (n = 13, 50%), thrombocytopenia (n = 6, 23.1%), and anemia (n = 2, 7.7%). Five patients (19.2%) experienced a pulmonary infection grade 3 or higher. Three patients (11.5%) experienced bleeding, and 2 patients (7.7%) experienced cardiovascular events. Cardiovascular events were resolved with treatment. Dose reduction occurred in 14 (53.8%) patients, and AEs were the most common reason.

Patients received R-CHOP intravenously and zanubrutinib orally in 21-day cycles for 6 cycles. Patients then received 2 subsequent cycles of rituximab and zanubrutinib maintenance treatment.

Lymphoma cells: © Dr_Microbe - stock.adobe.com

Patients were eligible for the trial if they were over 18 years old with treatment-naïve non-GCB DLBCL with extranodal involvement and an ECOG performance status of 2 or lower. Patients also needed a left ventricular ejection fraction 50% or higher, a creatinine clearance rate of 30 mL/min or higher, levels of alanine transaminase and aspartate transaminase 3 times the normal range or higher, absolute neutrophil count of 1.0 x 109/L cells or higher, platelet count of 50 x 109/L or higher, and hemoglobin of 8.0 g/dL or higher.

“This study provides evidence that ZR-CHOP regimen could enable more high-risk patients to achieve better efficacy at the end of the first-line treatment and may make it possible for some patients to get long-time remission in the first-line treatment,” study authors concluded.

In addition to these data, a 2022 study of evaluating the use of ZR-CHOP in the treatment 44 patients with double-expression DLBCL found that the regimen achieved a high response rate with tolerable toxicity.³

Ongoing studies are investigating the use of ZR-CHOP in subgroups of DLBCL, including in patients with gene abnormalities (NCT05290337) and high risk factors (NCT05887726).

REFERENCES:

1. Geng H, Jia S, Zhang Y, et al. (2023) Efficacy and safety of zanubrutinib plus R-CHOP in treatment of non-GCB DLBCL with extranodal involvement. Front Immunol. 2023;14:1219167. Published 2023 Aug 21. doi:10.3389/fimmu.2023.1219167

2. Zanubrutinib plus R-CHOP for patients with newly diagnosed untreated non-GCB DLBCL. ClinicalTrials.gov. Updated September 16, 2022. Accessed October 27, 2023. https://tinyurl.com/y6pw2zdb

3. He Q, Xie L, Zhao R, et al. Zanubrutinib plus RCHOP (ZR-CHOP) regimen achieves high complete response rate in the treatment of newly-diagnosed double-expression diffuse large B-cell lymphoma. Hemasphere. 2022;6(Suppl ):1087-1088. Published 2022 Jun 23. doi:10.1097/01.HS9.0000847668.08542.45