Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
adult, Clinical Practice (Health Services and Quality), Lymphomas, elderly, B Cell lymphoma, Combination therapy, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies, Adverse Events, Study Population, Human
Methods: Previously untreated DLBCL patients aged over 70 years old, or aged between 60 to 69 with ECOG score 2 to 4 were enrolled in this study. All patients received a triplet regimen of ZPR. Twenty-one days was a cycle. Zanubrutinib was given 160mg twice a day orally from day 1 to day 21. Rituximab was given 375mg/m2 intravenously on day 1. Polatuzumab vedotin was administered at a dosage of 1.8mg per kilogram intravenously on day 1. Patients would receive 6 cycles of ZPR regimen if assessed partial response (PR) or complete response (CR) after 3 cycles. If assessed CR after 6 cycles of ZPR, patients would receive zanubrutinib 160mg twice a day alone for another 6 cycles. Whole body 18F-FDG PET/CT scan or contrast-enhanced CT scan of cervical, thoracic, abdominal and pelvic parts was scheduled every 3 cycles. Treatment response was assessed by 2014 Lugano response criteria. Adverse events were graded by CTCAE 5.0. The primary endpoint is overall response rate (ORR) after 6 cycles of ZPR. The secondary endpoints are CR rate after 6 cycles of ZPR, and 2-year progression-free survival (PFS). Other endpoint is safety (Figure 1).
Results: Twelve patients were enrolled in our study until Jul 24, 2023. Median age was 75 (range: 67-87). Six patients were female and six patients were male. Nine (75%) patients were classified non-GCB type according to cell of origin by Hans algorithm. Nine (75%) patients were assessed stage Ⅲ to Ⅳ by Ann Arbor staging system. Nine (75%) patients had an international prognostic index (IPI) score of 2 or more. One (11%) patient had double-hit risk factor in 9 patients with gene rearrangement results. Six (75%) patients had MYD88 L265P mutation in 8 patients with sequencing results. After a median follow up of 2.1 months, four patients had PET/CT assessment results after 3 cycles of ZPR, and four (100%) of them achieved CR. The ORR after 3 cycles of ZPR regimen was 100% (Figure 2). Grade 3 to 4 adverse events occurred in two patients, that one patient had grade 3 aspartate aminotransferase increase and alanine aminotransferase increase, and the other patient had grade 3 pneumonitis. Grade 1 to 2 adverse events included neutrophil count decrease (16%), dizziness (8%), and epistaxis (8%). All patients recovered from adverse events under best supportive care. There was no discontinuation of ZPR regimen due to severe adverse events.
Conclusion: Based on these results in our study, ZPR regimen showed rapid and deep response in previously untreated frail and elderly DLBCL patients with manageable safety profiles. We registered and initiated a phase 2b trial (NCT05940064) to further evaluate the efficacy and safety of ZPR regimen as first-line treatment for this population. Ongoing treatment and follow up of these twelve patients will also be further updated.
Disclosures: No relevant conflicts of interest to declare.
OffLabel Disclosure: zanubrutinib in first-line treatment of diffuse large B-cell lymphoma
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