Real-World Experience with Polatuzumab-R-Based Regimens in Previously Untreated Large B-Cell Lymphoma: A Study by the Croatian Cooperative Group for Hematologic Diseases (KROHEM)
Materials and Methods/Case Presentation/Objective:
We conducted a retrospective, multicenter study across 16 Croatian centers, including patients treated between November 1, 2024, and November 1, 2025. To reflect routine clinical practice, inclusion was independent of age, International Prognostic Index (IPI) score, or ECOG performance status. Data were analyzed for overall response rate (ORR), complete remission (CR), progression-free survival (PFS), overall survival (OS), and toxicity profiles.
Results/Description/Main Outcome Measure(s):
A total of 201 patients (106 males, 95 females) were included, with a median age of 69 years (range 19-88). The cohort represented a high-risk population: 68.1% (n=137) had Stage IV disease, 64.7% (n=130) had an IPI score of 3-5, and 38.3% (n=77) had a poor performance status (ECOG ≥ 2), including 29 patients with ECOG 3-4. Regarding histological subtypes, patients were classified as non-germinal center B-cell like (non-GCB, n=81), germinal center B-cell like (GCB, n=72), DLBCL NOS (n=27) high-grade B-cell lymphoma (n=12), and other subtypes (transformed FL n=3, PMBL n=6). Regarding treatment, 134 (66.7%) patients received standard Pola-R-CHP, while 67 (33.3%) received adapted regimens, including Pola-R-mini-CHP (n=24), Pola-R-CHEP (n=18), Pola-R-DA-EPOCH(n=12), and Pola-R-CEP (n=12). CNS prophylaxis was administered to 25 patients(23 high dose MTX), and 8 received consolidative radiotherapy.
After a median follow-up of 7 months, the overall survival (OS) rate was 83.1% and the event-free survival (EFS) rate was 77.1%. Among the total cohort, 163 patients were evaluable for response, while 38 patients are still early in their treatment course and awaiting their first post-therapeutic evaluation. Among these 163 evaluable patients, the overall response rate (ORR) was 90.8% (148/163), with a complete remission (CR) rate of 65% (106/163) and partial remission (PR) rate of 26%( 42/163)
Prognostic analysis showed that the IPI score provided strong stratification (p < 0.001); low-risk patients (IPI 0-1) reached 100% OS and EFS, the low-intermediate group (IPI 2) achieved 92.3% OS and 90.4% EFS, and the high-intermediate group (IPI 3) reached 94.1% OS and 84.3% EFS, while high-risk patients (IPI 4-5) had significantly lower outcomes (OS 66.3%; EFS 58.8%). Age impacted OS (p=0.046) but not EFS, and ECOG status remained the strongest predictor (p < 0.001).
Regarding safety, grade 3 or higher adverse events (AEs) occurred in 40.5% (n=81) of patients. The most frequent grade 3/4 hematological toxicities were neutropenia (33%), anemia (15.5%), and thrombocytopenia (12.5%). Febrile neutropenia was reported in 15.5% of cases, with a 1.5% fatal outcome rate. Non-hematological grade 3 or higher toxicities included infections (11%) and peripheral neuropathy (6%). Hospitalization due to AEs was required for 17.5% of patients, while 7% required polatuzumab dose reduction. One patient developed secondary AML.
Conclusion(s).:
We report one of the largest multi center real-world experiences to date, confirming that Pola-R-based therapy is highly effective in a broad unselected patient population, including high-risk and "unfit" subgroups typically excluded from clinical trials. Our study supports the effectiveness and safety of these regimens in daily clinical practice, demonstrating their feasibility even in elderly patients requiring treatment adaptations.
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