The Polarix Trial and the Rise of Polatuzumab-RCHP

By Dr. Luke Fletcher

Willamette Valley Cancer Institute & Research Center 

 

Combination chemoimmunotherapy with the chemo regimen R-CHOP (Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) has long stood as the standard of care for diffuse large B-cell lymphoma. Many combinations and drugs have attempted to improve on this without avail until now. Polatuzumab vedotin-piiq, an antibody-drug conjugate in combination with R-CHP (Rituximab, cyclophosphamide, doxorubicin, prednisone), was just approved for adults with untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index (IPI) score of two or greater.^1,2 This was based on the phase 3 POLARIX trial.

 

The phase 3 POLARIX trial compared R-CHOP vs. Pola-RCHP randomized 1:1 to each arm. The primary endpoint was progression-free survival, which was significantly reduced with Pola-RCHP compared to R-CHOP (PFS 76.7% vs. 70.2%, HR, 0.73; P < .02).³  Important considerations were made in the subtypes included in the study, namely DLBCL NOS, HGBCL with MYC and BCL2 and/or BCL6 rearrangements, HGBL NOS, and other low-grade B-cell lymphomas, including T-cell/histiocyte-rich LBCL, Epstein–Barr virus–positive DLBCL, ALK-positive LBCL, and HHV8-positive DLBCL. Side effects were similar between groups.

 

These developments suggest a major change in diffuse large B cell lymphoma treatment. As stated, R-CHOP has been the standard for decades. The implementation will be interesting as there is much discussion of cost concerns that will have to be navigated in certain places. In addition, some have noted the lack of overall survival benefit to date. However, the primary endpoint of PFS was met, and this benefit could be significant in terms of a long-term cure, recommending a major milestone in lymphoma research.

 

References:

 

1. Roche Pharmaceutical. “Polivy (Polatuzumab vedotin-piiq).” U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761121s008lbl.pdf. Revised April 2023. Accessed 21 April 2023.

2. Center for Drug Evaluation and Research. “FDA Approves Polatuzumab Vedotin-Piiq for Previously Untreated Diffuse.” S. Food and Drug Administration, FDA, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-previously-untreated-diffuse-large-b-cell-lymphoma-not. 19 April 2023. Retrieved 21 April 2023.

3. Tilly H, Morschhauser F, Sehn LH, et al. “Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma.” N Engl J Med. 2022 Jan 27, 86(4):351-363. doi: 10.1056/NEJMoa2115304. Epub 2021 Dec 14. PMID: 34904799.