Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin and Steroids (PolaRCHP) in Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL): Real-Life Experience in Greece
Authors: Vassilakopoulos Theodoros P. , Arapaki Maria Panagiota , Apostolopoulou Christina , Kaiafa Georgia , Mpanti Anastasia , Giatra Chara , Verrou Evgenia , Ioakeim Maria Anastasia , Triantafyllou Evangelia Fedra , Makris Michael-Evangelos , Anastasiadis Athanasios , Piperidou Alexia , Liaskas Athanasios , Delatola Maria , Koutsi Aikaterini , Xanthopoulos Vasileios , Sachanas Sotirios , Katodrytou Eirini , Bouzani Maria , Siakantaris Marina , Panayiotidis Panayiotis , Angelopoulou Maria , Papageorgiou Sotirios G. 
Published: December 2024

Background: The POLARIX trial demonstrated that Pola-R-CHP provided superior disease control than R-CHOP in previously untreated DLBCL with an international prognostic index (IPI) ≥2 and performance status (PS) ≤2, without however an overall survival difference so far. The difference in progression free survival (PFS) was marked in selected subgroups of patients, mainly defined by cell of origin (COO), age, and IPI. After &gt;15 years of R-CHOP treatment, Pola-R-CHP has provided another strong standard of care (SoC). Although POLARIX was limited to patients up to 80 years old (yo) with IPI ≥2 and PS ≤2, the official indication of Pola-R-CHP is unrestricted within the range of previously untreated DLBCL. Real-life data will be very useful to explore the efficacy of Pola-R-CHP in the entire spectrum of patients with DLBCL.

Aims: We sought to evaluate the efficacy of Pola-R-CHP in a real-life setting across 12 Hellenic centers.

Methods: So far 74 patients with previously untreated DLBCL were registered in our database.Based on the marked superiority of Pola-R-CHP over R-CHOP in patients with non-GCB cell-of-origin and those with IPI ≥3, many centers in Greece preferentially adopted this new SoC in these subgroups, which were overrepresented. Patients &gt;80 yo could still receive Pola-R-miniCHP and gemcitabine replaced doxorubicin in 3 patients with prohibitive cardiac comorbidities. Freedom From Progression (FFP) was defined as the time between treatment initiation and death during treatment, primary refractoriness or relapse. Progression Free Survival (PFS) was defined as FFP plus death of any cause in first complete remission.

Results: The median age of the 74 pts was 72.5 years (range 23-89; 81% &gt;60 yo and 24% &gt;80 yo), 53% were males, 68% hade stage III/IV, 51% had B-symptoms, 45% had PS≥2 [including 18% with PS 3-4 (n=13)], 43% had ≥2 extranodal sites, 82% elevated LDH, 70% had anemia and 80% had a non-GCB COO. IPI was 1,2,3,4 and 5 in 10%, 13%, 35%, 28% and 13% respectively. So far 10 patients have died during treatment (13.5% - toxic deaths, early disease-related complications or progression; 8 with PS 2 and 2 with PS 4)), 15 (20.3%) had primary resistant disease (stable or progressive disease at end-of-treatment evaluation or earlier) and 1 (1.4%) experienced a relapse. The 2-year FFP for the whole cohort was 56% with no difference for patients ≤80 and &gt;80 yo. Impaired PS was an extremely unfavorable prognostic factor with 2-year FFP of 80% vs 19% for PS 0-1 vs ≥2 (p=0.001). Similarly B-symptoms predicted for a lower 2-year FFP (66% vs 45%, p=0.02). No other prognostic factors could be demonstrated in this dataset. Very high IPI (4-5) and noon-GCB COO were associated with numerically but not statistically inferior FFP.

Conclusion: We report the Hellenic experience with Pola-R-CHP in a very unfavorable (rather negatively selected) real-life patient population with untreated DLBCL. Pola-R-miniCHP was feasible and effective in very elderly patients (&gt;80 yo) who were not included in POLARIX. Pola-R-CHP was very effective in patients with PS 0-1 but its efficacy was limited in patients with impaired PS (45% of all patients vs 16% in POLARIX, including 19% PS 3-4 who were ineligible for POLARIX). This was reflected in the increased percentage of early deaths as a result of selection of patients with very unfavorable profile. The Hellenic database is currently further enriched in order to define the patterns of selection of patients for Pola-R-CHP and investigate the outcomes in the real-life in specific patient subgroups.