PB2097: ZANUBRUTINIB PLUS RITUXIMAB FOR THE TREATMENT OF ELDERLY UNFIT PATIENTS WITH PREVIOUSLY UNTREATED DIFFUSE LARGE-B CELL LYMPHOMA

Abstract

Background: Diffuse Large B-cell lymphoma (DLBCL) is common in the elderly patients, Some elderly patients can not tolerate the standard dose of R-CHOP due to age, poor physical condition, and severe complications. The overall response rate of elderly unfit DLBCL patients who received a reduced dose R-CHOP regimen was only 60%. It is extremely important to explore new therapeutic options. Zanubrutinib is a Bruton tyrosine kinase (BTK) inhibitor which was still in an exploratory phase in patients with DLBCL.The efficacy of Zanubrutinib plus Rituximab in elderly unfit Patients with DLBCL is still unknown. Aims: This study was conducted to investigate the efficacy and safety of Zanubrutinib plus Rituximab in elderly unfit Patients With Previously Untreated Diffuse large-B cell Lymphoma in China. Methods: In the present study, a prospective, single-arm,single-center study was conducted (CHiCTR-2000039342). patients who fulfil the inclusion criteria were enrolled. Inclusion criteria: patients aged ≥65 years, pathologically confirmed DLBCL,and assessed unfit by Comprehensive Geriatric Assessment(IACA). Unfit patients defined as follows: i.e. IADL score ≤7, or age >75 years, or CCI score ≥3, or serum albumin <3.4 g/ml. Patients enrolled were planed to treat with Zanubrutinib combined with rituximab (Zanubrutinib 160 mg orally twice daily and rituximab 375 mg/m2 day1 iv, every 28 days, ZR regimen), for a total of eight courses. After induction therapy, maintenance treatment with Zanubrutinib 160mg orally twice daily was given until disease progression or unacceptable toxicity. Efficacy was evaluated by PET/CT or enhanced Computed Tomography scan every two months, treatment-related adverse effects were evaluated in every one month. This study was approved by the Ethics Committee of Beijing Hospital, National Center of Gerontology, Beijing, China. Results: From July 2020 to December 2021, a total of eight elderly unfit DLBCL patients were enrolled. one patient was 72 years old with IADL score of 6, CCI score of 4. the other seven patients were aged over 80 years. the most common comorbidities were cardiovascular disease, hypertension, diabetes.The female to male ratio was 6:2. four patients were classified as GCB pathological subtype, six patients were diagnosed with stage III-IV. At a median follow up of 8 months (2-19months). two patients achieved complete response(CR), and remained in CR at months 8. four patients achieved partial response(PR), with one patient disease progression(PFS 8 months), one patient achieved stable disease (SD) after 2 cycles and have disease progression after 4cycles, with a progression-free survival (PFS) of 4 months. one patient was refractory to treatment and withdrew after 2 cycles. One patients died due to disease progression, with overall survival(OS) of 11 months, ZR regimen was well-tolerated, with grade 2 urinary tract infections in 4/7 patients, grade 2 respiratory infections in 2/7, grade 1 Petechial hemorrhages in 3/7, grade 2 skin rash in 2/7, and grade 2 deep vein thrombosis in 1/7. No grade 4 or higher adverse events were observed. Seven patients had a dose reduction due to toxicity. The regular doses of Zanubrutinib can be tolerated was 160 mg qdA1-80mg qdP1. Two patients had discontinued Zanubrutinib due to adverse events for one to three weeks. Image:Summary/Conclusion: Zanubrutinib in combination with Rituximab may be a well-tolerated and effective regimen in elderly unfit DLBCL patients. Dose reduction may be required for some patients to improve tolerability. A large sample size clinical trial is needed to further validate this conclusion in the future.