Background Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype, with incidence rising progressively with age. Although R-CHOP remains the standard first-line therapy, significant toxicities frequently limit its tolerability in elderly or frail patients. While polatuzumab vedotin-based regimens have demonstrated favorable efficacy and safety profiles in trials, data on individualized strategies remain limited.

Methods This retrospective study enrolled newly diagnosed DLBCL patients treated at Henan Cancer Hospital between March 2023 and March 2025. Patients aged ≥60 years or with ECOG performance status of 2–4 were included if deemed unfit based on comprehensive geriatric assessment (CGA) or significant comorbidities. Efficacy was evaluated per Lugano 2014 criteria; adverse events (AEs) were graded according to NCI CTCAE v5.0.

Results Fifty-four frail patients with newly diagnosed DLBCL met inclusion criteria. Baseline characteristics included: median age 72 years (range 61–90); Ann Arbor stage III–IV disease (81.5%, 44/54); International Prognostic Index (IPI) score ≥3 (61.0%, 33/54); bulky mass ≥7.5 cm (24.1%, 13/54). Molecular profiling revealed non-germinal center B-cell (non-GCB) subtype in 63.0% (34/54) and double-expressor lymphoma (DEL) in 37.0% (20/54). High-risk features encompassed: Richter transformation from indolent lymphoma (9.3%, 5/54), bone marrow involvement (29.6%, 16/54), CNS/testicular infiltration (7.4%, 4/54), and hemophagocytic lymphohistiocytosis at diagnosis (5.6%, 3/54). Comorbidity burden was substantial, with 79.6% (43/54) having ≥2 chronic illnesses (e.g., diabetes, hypertension, ischemic heart disease, COPD). Treatment allocation: pola-BTKi-rituximab (pola-BTKi-R, chemotherapy-free, n=21), pola-lenalidomide-rituximab (pola-R2, chemotherapy-free, n=11), pola-rituximab-miniCHP (pola-R-miniCHP, chemotherapy-light, n=22).

All patients completed ≥3 treatment cycles with interim response assessment. The overall response rate (ORR) was 90.7% (49/54), with complete response (CR) achieved in 53.7% (29/54). CR rates by regimen were: 61.9% (13/21) for pola-BTKi-R, 54.5% (6/11) for pola-R2, and 45.5% (10/22) for pola-R-miniCHP. Among 32 patients completing ≥6 cycles (end-of-treatment analysis), ORR was 90.6% (29/32) and CR rate increased to 84.4% (27/32). Regimen-specific CR rates were: 91.7% (11/12) for pola-BTKi-R, 85.7% (6/7) for pola-R2, and 76.9% (10/13) for pola-R-miniCHP. With a median follow-up of 10 months, median PFS and overall survival (OS) were not reached.

Among DEL patients (n=20), interim analysis after three cycles revealed an ORR of 90% and CR rate of 55%. In those completing six cycles (n=12), both ORR and CR reached a remarkable rate of 100%.

Of nine patients identified as MCD subtype by next-generation sequencing, all seven receiving pola-BTKi-R achieved an ORR of 100%, including a CR rate of >85% at interim.

Grade 3–5 AEs: neutropenia (20.4%, 11/54; resolved with G-CSF support); pneumonia (16.7%, 9/54)—eight recovered with antibiotics, one death in a diabetic patient with resistant infection. Grade 1–2 AEs comprised thrombocytopenia (11.1%, 6/54), elevated ALT/AST levels (7.4%, 4/54), rash (5.6%, 3/54), and peripheral neuropathy (3.7%, 2/54). No BTKi-specific toxicities such as atrial fibrillation or severe bleeding were observed in the group.

Conclusions Polatuzumab vedotin-based regimens show promising efficacy and manageable toxicity in elderly/unfit DLBCL, with notable benefits in high-risk subgroups—particularly MCD patients receiving pola-BTKi-R. Further validation with larger sample sizes and longer follow-up periods is required.

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2025
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