According to a prolonged 5-year follow-up of the POLARIX trial, treatment with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) showed durable and significant progression-free survival (PFS) benefit vs R-CHOP among patients with intermediate- or high-risk diffuse large B-cell lymphoma (DLBCL).

These results were presented by Gilles Salles, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 66^th ASH Annual Meeting in San Diego, California.

“Safety profiles remained similar between arms, and no new safety signals were identified,” Salles and coauthors wrote, “These outcomes confirm Pola-R-CHP as a standard of care for patients with previously untreated intermediate- or high-risk DLBCL.”

Transcript:

Hello, my name is Gilles Salles from Memorial Sloan Kettering and I was happy doing the ASH 2024 meeting to report the updated result of the POLARIX study. As you may recall, the study was the randomized study in newly diagnosed patient with DLBCL assessing the role of polatuzumab vedotin in the first-line treatment of this patient. So a double-blind randomized comparison of R-CHOP versus Pola-R-CHP. The result were published in the New England a little bit more than 2 years ago, and this was with 2 years of follow-up.

The primary end point was met with a benefit in time of progression-free survival. It was very important to know if this result were sustainedd, and that's the result we presented this morning with now 5 years of follow-up of this population of more than 800 patients. What we show is that the difference in progression-free survival that was initially observed is sustained and confirmed with the hazard ratio of .77 at 5 years, and the 2 curves are clearly parallel.

This is I think, excellent news for the patient. The same is true for the prolonged disease-free survival. As you may recall, there was no overall survival benefit and the 2 curves were clearly super impossible at 2 years. What we observed at 3 years is there is no statistical difference still in term of overall survival. The hazard ratio was 0.94 at the 2 years update, it's now .85 and there is almost a 3% difference in overall survival, again, non-statistically significant.

We however, looked at the cause of deaths of patient and found that there were more lymphoma-related deaths in our CHOP-treated patient while the causes of deaths that were unrelated to lymphoma were balanced between the 2 study arm. Furthermore, looking at an expanded population of patient both in the global study and in extension study in China, we looked at the trend in term of lymphoma related deaths and we observed that while there was clearly [ ] during the first 2, 3 years of the study, they tend to diverge favoring against POLA-R-CHP, so it's possible that with a longer follow up we might or we might not observe a difference.

We look at the subgroups of patient with different characteristics. These are exploratory analysis. They don't necessarily indicate which patient should be treated, but this is an indication that in patient, for instance with an International progressive index of more severe disease, the difference in term of progression-free survival at 5 years is 10% and in term of overall survival is 5%. Similar trend is sent for patient with high grade B-cell lymphoma or double of triple hit. And for patient swith a molecularly defined A, B, C subtype activated B-cell set time, the difference in term of PSFS is 25% and in term of overall survival, 15%. They should be taken with caution. These are exploratory analyses, but an indication that probably POLA-R-CHP benefit more the more difficult to treat patient overall.

In term of safety, there were no major differences. Slightly tiny, little bit more of hematological toxicity, no more peripheral neuropathy and slightly more infections. At five years we observed that there were no more cardiac events, probably slightly less and less second cancer in patients treated with POLA-R-CHOP.

Overall we were happy to see that the 5years result confirm the benefit in term of disease control of polar chip over our chop. Still no overall survival difference at though it's possible that the curve may separate in the future.

I think these are good results for our patients and for continuing to progress in the treatment of newly diagnosed diffuse large B-cell lymphoma. Thank you for your time.
 

Source:

Salles G, Morschhauser F, Sehn LH, et al. Five-Year Analysis of the POLARIX Study: Prolonged Follow-up Confirms Positive Impact of Polatuzumab Vedotin Plus Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) on Outcomes. Dec 7-10, 2024; San Diego, CA. Abstract: 469