John Burke, MD, Rocky Mountain Cancer Centers, Aurora, Colorado, discusses the phase 3 POLARIX study on polatuzumab vedotin with rituximab, cytclophosphamide, doxorubicin, and prednisone (pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for patients with previously untreated diffuse large B-cell lymphoma (DLBCL). These data were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

Transcript

Hi, my name is John Burke at Rocky Mountain Cancer Centers in Aurora, Colorado. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard treatment for frontline therapy of DLBCL for decades now. Many trials have attempted to approve upon it without success.

This trial is looking at polatuzumab vedotin, which is an antibody-drug conjugate targeting CD79b. Preliminary data had shown that the combination of polatuzumab plus R-CHP (polatuzumab vedotin-piiq with rituximab, cyclophosphamide, doxorubicin, and prednisone) appears to have strong activity in DLBCL. This was a randomized phase 3 trial for previously untreated DLBCL. Patients, again, were randomized to R-CHOP or pola-R-CHP.

The primary endpoint of the study was progression-free survival (PFS). The key finding here was that pola-R-CHP significantly improved PFS as compared with R-CHOP. The response rates were a little bit higher with pola-R-CHP. So far, we have not seen an overall survival (OS) difference.

In terms of additional outcomes patients required less additional therapy after completion of treatment in the pola-R-CHP arm. For example, there was less need for additional radiation therapy, less need for additional systemic therapy, less need for salvage stem cell transplant. All of these were potential clinical benefits that we saw in the trial.

The toxicity profile was relatively comparable between the 2 arms. There's a little bit more neutropenia in the polatuzumab group. Interestingly, neuropathy was very similar between the 2 groups, even though neuropathy is a known toxicity of polatuzumab.

Overall, we feel that the balance here is that polatuzumab achieved a significant clinical benefit in terms of improving PFS and reducing the need for subsequent therapies at not much of a cost in terms of added toxicity profile.

This may position the pola-R-CHP regimen to be perhaps a new option for patients with previously untreated advanced DLBCL.

Many trials in frontline management of large cell lymphoma have failed. This has been a graveyard for drugs trying to beat R-CHOP. For the first time now, this is an improvement.

In one sense, no, it's not surprising because we've seen that polatuzumab is an effective drug and adding polatuzumab to bendamustine and rituximab improved OS in a randomized trial in relapsed (DLBCL) patients.

That has never been done before. In that sense, it's not surprising that this is a very effective drug, and it improved outcomes, but it's just this is a hard endpoint to achieve. This trial seemed to have succeeded where many others have failed before it, and so that's exciting for the field.

This is really a question of should this become a new standard for frontline management of DLBCL. This needs to go through peer review and regulatory authority review and the whole oncology community needs to digest these data and think about this moving forward.

As for next steps beyond this, probably not to my knowledge polatuzumab is being studied in many other areas, but as for this particular research, this is a phase 3 trial. This is the end of this particular investigation here other than long-term follow-up. We will be continuing to these patients long-term for OS.