Background:

DLBCL is the most prevalent aggressive form of B-cell lymphoma. Modern molecular profiling subdivides DLBCL into biological distinct subtypes, and the combination of staging, immunohistochemistry (IHC), and cytogenetic studies further stratifies patients (pts) into standard vs. high-risk categories. A high international prognostic index (IPI) score, concomitant increased expression of BCL2 and CMYC by IHC (Double expressor lymphoma [DEL]), the presence of balanced translocation involving the C-MYC proto-oncogene alone (C-MYC re-arrange DLBCL/High grade B-cell lymphoma) or in combination with the BCL-2 proto-oncogene (Double hit lymphoma [DHL]) are associated with a more aggressive clinical behavior and poor outcomes. Until recently, high-risk DLBCL pts were treated with R+DA EPOCH. The POLARIX clinical trial established the superiority of Pola + R-CHP over rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R+CHOP) in newly diagnosed advance stage DLBCL. It is unclear if Pola + R-CHP can substitute R+DA EPOCH is DLBCL with high-risk features.

Objective

To this end, we compared the clinical outcomes of newly diagnosed DLBCL with high-risk features treated with either R+ DA EPOCH or Pola + R-CHP at our institute.

Methods

We conducted a single-center, retrospective study comparing the anti-tumor activity of R+DA EPOCH vs. Pola + R-CHP in high-risk features DLBCL pts treated at our Institution over the last 2 decades. Patient demographics, clinical, pathological (cell of origin [COO], DEL status, c-MYC translocation status, etc.), and treatment characteristic were extracted. The Pola + R-CHP pts were matched to R+DA-EPOCH pts in a 1:2 ratio using a propensity score derived from the following variables: Age at diagnosis, Sex, Double Expressor status, Double Hit status, COO, Stage, and IPI score. Differences in clinical endpoints such as overall repose (ORR), complete remission (CR), and partial remission (PR) rates or frequency of grade 3-4 toxicities (coded as per CTCAE v5.0) were compared by Fisher T-test during and at the end of treatment. Differences in progression free survival (PFS) and overall survival (OS) between treatment groups were compared by log-rank test.

Results

A total of 261 pts were identified(Pola + R-CHP = 24 and R+DA-EPOCH N=237). Sixty-nine high-risk DLBCL were included in the propensity score analysis, 23 received Pola + R-CHP and 46 R+DA EPOCH. Baseline demographic characteristics were similar between cohorts (i.e. median age and gender distribution). High-IPI score (>3) was observed in 44% and 54% of the pts treated with Pola + R-CHP and R+ DA EPOCH respectively. Per Han's algorithm, 61% of Pola + R-CHP pts and 57% of R-DA EPOCH pts had a non-Germinal center B-cell (non-GCB) phenotype. DEL and DHL distribution was similar between pts treated with Pola + R-CHP (30%/4.3%) or R+DA EPOCH (28%/6.5%). ORR, CR (89% vs. 78%, P=0.73), and PR rates were similar between Pola + R-CHP and R+DA EPOCH treated pts. At 24 months, PFS rates was 93.8 % (CI 82.6–100) in pts treated with Pola + R-CHP vs. 56.4 % (CI 43.3–73.4) for those treated with R+DA EPOCH (P=0.013). In addition, the OS rate was 100% for Pola + R-CHP treated pts in contrast to 63 % (50–79.4) for treated with R+DA EPOCH (P=0.01). The incidence of grade 3 or higher hematological toxicities was lower in Pola + R-CHP than R+DA EPOCH treated pts: grade ≥ 3 febrile neutropenia 0 % versus 30 % (P=0.003), thrombocytopenia 0 % versus 57 % (P<0.001), and anemia requiring transfusion 17 % versus 63 % (P< 0.001). Non-hematologic events were also less frequent in Pola + R-CHP vs. R+DA EPOCH treated pts: neuropathy 0 % vs 39 % (p < 0.001) and venous thrombo-embolism 4% vs. 24 % (P= 0.050). Cardiac toxicity and ICU admission rates were rare (< 5%) in both arms.

Conclusions

This analysis is, to our knowledge, the first known comparison between rigorous matched balanced cohorts of Pola + R-CHP and R+DA EPOCH treated high-risk DLBCL. Our data suggest a comparable response rate between both regimens. Of interest, our analysis demonstrates a superior 2-years PFS/OS and markedly lower hematological toxicities favoring Pola + R-CHP over R+DA EPOCH in this group of high-risk DLBCL pts. Our findings support further real-world data analysis comparing Pola R+CHP vs. R+DA EPOCH in other academic institutions and the use of Pola R+CHP in high-risk DLBCL pts, especially DEL.

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2025
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