Add-on polatuzumab vedotin boosts survival, responses in R/R DLBCL

All key survival and response endpoints are met in the phase III POLARGO trial evaluating polatuzumab vedotin (Pola) plus rituximab and gemcitabine and oxaliplatin (R-GemOx) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for stem cell transplant.

Incorporating the CD79b-targeted antibody-drug conjugate Pola into the R-GemOx regimen significantly improved overall survival (OS), with a 40-percent relative reduction in the risk of death  (stratified hazard ratio [HR], 0.60, 95 percent confidence interval [CI], 0.43–0.83; log-rank p=0.0017) compared with R-GemOx only. [EHA 2025, abstract S101]

“We did indeed achieve our primary endpoint of an improvement in OS with the addition of Pola to R-GemOx,” said Professor Matthew Matasar from the Rutgers Cancer Institute, New Brunswick, New Jersey, US. “The median OS [improved] from 12.5 to 19.5 months, and the likelihood of being alive at 2 years improved from 33.2 percent to 44 percent.”

These improvements were demonstrated at a median follow-up of 24.6 months.

PFS, response rates

There was also a significant improvement in progression-free survival (PFS), as well as higher complete response (CR) and overall response rates (ORR), with the experimental regimen vs R-GemOx.

After a median follow-up of 18.7 months, median PFS with Pola-R-GemOx was 7.4 months vs 2.7 months with R-GemOx (stratified HR, 0.37, 95 percent CI, 0.27–0.51; log-rank p<0.0001).

At the end of treatment with up to eight cycles, 40.3 percent of patients in the Pola-R-GemOx arm achieved a CR as assessed by an independent review committee (IRC) using PET-CT vs 19 percent in the R-GemOx arm. Including those with partial responses, the IRC-assessed ORR was 52.7 percent vs 24.6 percent, respectively.

Pola-R-GemOx vs Pola-BR

POLARGO was a two-phase trial consisting of a safety run-in (n=15) that assessed the safety and tolerability of Pola-R-GemOx, followed by a randomized phase (n=255) comparing Pola-R-GemOx vs R-GemOx for efficacy.

Pola had been approved as part of a regimen with bendamustine and rituximab (Pola-BR) for R/R DLBCL in over 90 countries worldwide. The evidence supporting approvals of Pola-BR was primarily from the phase Ib/II GO29365 trial evaluating Pola-BR vs BR, with CR rate as the primary endpoint. [J Clin Oncol 2020;38:155-165; Cancer Sci 2021;112:2845-2854]

“I think our results are quite comparable with those from GO29365 in terms of CR rate and ORR,” commented Matasar. “Particularly in subsets of patients such as those who were primary refractory and those who were refractory to the most recent line of therapy, we saw a tremendously prolonged PFS in GO29365, as well as a significantly prolonged OS in combination with R-GemOx in POLARGO.”

However, Matasar noted that patients in GO29365 were “slightly more heavily pretreated”, as they had a median of two prior lines of therapy vs one in POLARGO.

An alternative bendamustine-free regimen

“The POLARGO data reported herein reinforce the benefit of adding Pola to chemoimmunotherapy in a variety of clinical settings, now in combination with R-GemOx,” Matasar concluded.

“This gives clinicians a potentially new tool in the treatment of R/R disease, a different chemotherapy backbone other than bendamustine, and the ability to avoid bendamustine-related impacts on subsequent T cell-engaging therapies,” he added.