Pola-R-CHP

R-CHOP has been compared with Pola-R-CHP. Polatuzumab is an antibody-drug conjugate composed of an anti-CD79B monoclonal antibody attached to vedotin (monomethyl auristatin E), a microtubule inhibitor.

Evidence (Pola-R-CHP):

The follow-up interval was too short to establish whether the 6% improvement in the PFS rate will plateau or improve after 2 years, and there is no evidence of OS advantage. Nonetheless, updated outcomes with a median follow-up over 3 years showed continued improvement of PFS, prompting the U.S. Food and Drug Administration (FDA) to approve Pola-R-CHP. Pola-R-CHP is the first regimen in over 20 years to be approved by the FDA as a therapy for patients with noncontiguous stage II, stage III, and stage IV disease. The new regimen is more than twice the cost of R-CHOP using acquisition prices in 2022, and polatuzumab may not be available worldwide.

The Pola-R-CHP regimen demonstrated substantial efficacy for patients with DLBCL non–germinal center B-cell (GCB)-origin tumors, predominantly those with the ABC (activated B-cell) subtype.[4] In the POLARIX trial, the HRPFS for Pola-R-CHP versus R-CHOP in patients with ABC-subtype tumors was 0.34 (95% CI, 0.13–0.85), and the HROS for those patients was 0.27 (95% CI, 0.06–1.26). In contrast, no such benefit was observed for patients with GCB-subtype tumors in this trial. For Pola-R-CHP, the HRPFS was 1.18 (95% CI, 0.75–1.84), and the HROS was 1.64 (95% CI, 0.87–3.07). This differential efficacy in favor of the non-GCB or ABC subtype was seen in five prospective phase I and II trials of the Pola-R-CHP regimen in patients with relapsed or refractory disease, with a combined analysis of data showing a level of significance P < .001.[4] Combining the data for a randomized phase II trial studying Pola-R-CHP in patients with relapsed or refractory disease with data from the POLARIX trial in patients with previously untreated disease, the HRdisease relapse/progression/death was 0.25 for patients with ABC-subtype tumors and 0.98 for patients with GCB-subtype tumors (P < .001).[4] The only exception to this observation is the clear benefit of Pola-R-CHP in GCB patients with double-hit variants (MYC gene and BCL2 gene). Given the increased rates of febrile neutropenia in patients who receive Pola-R-CHP and the significant financial toxicity, it is reasonable to consider R-CHOP as a standard regimen for patients with GCB-subtype DLBCL without a double-hit variant. However, assessing the GCB subtype using commercially available immunophenotyping is less accurate than using the molecular genetic signatures used in the POLARIX study. Some patients may miss the PFS benefit of polatuzumab. Some clinicians err on the side of using Pola-R-CHP for GCB subtype when patients have other high-risk features (e.g., CD5 positivity or involvement in two or more extranodal sites).