Polatuzumab Vedotin, zanubrutinib and rituximab (Pola-ZR) achieved rapid and deep response in untreated frail and elderly DLBCL.

First-line treatment balancing efficacy and safety is urgently needed for frail and elderly diffuse large B-cell lymphoma (DLBCL) patients. We designed a triplet chemo-light regimen, Pola-ZR, in previously untreated frail and elderly DLBCL patients to assess the efficacy and safety in a prospective DLBCL cohort (NCT06203652). Polatuzumab vedotin was given 1.8 mg/KG intravenously on day 1, zanubrutinib 160 mg twice a day orally from day 1 to day 21, and rituximab 375 mg/m² intravenously on day 1. Twenty-one days were a cycle. If assessed complete response (CR) after 6 cycles, patients would receive zanubrutinib alone for another 6 cycles. PET/CT or contrast-enhanced CT scan was scheduled every 3 cycles. The primary end point was overall response rate (ORR) after 6 cycles. Twenty-four patients were enrolled from 01 Apr 2023 to 20 Dec 2023. Median age was 73. Sixteen (66.7%) patients had an international prognostic index score of 3 to 5. After a median follow-up of 10.2 months, the CR rate and ORR after 6 cycles was 83% and 83%. Non-responders had high total metabolic tumour volume. Lung infection was the major safety concern. PJP prophylaxis was recommended. Pola-ZR regimen showed rapid and deep response with manageable safety profiles in both GCB and non-GCB subtypes.