ASH 2024 | The approval of Pola-R-CHP for DLBCL and subpopulations that benefit the most

Over the last year, the FDA has approved a combination of polatuzumab vedotin an antibody-drug conjugate targeting CD79B with R-CHP based on results of a very large randomized Phase III trial called the POLARIX trial where patients with previously untreated large B-cell lymphoma in advanced stage or stage 2 bulky received either frontline polatuzumab-R-CHP or R-CHOP. And patients have to have as a reminder an IPI of two or higher to be eligible for this trial, which is also reflected in the current label. In this study the primary endpoint was significantly longer progression-free survival was met, though the absolute difference was only around 7.5%, which has been a major criticism over the last few years. But what we have learned, thanks to very in-depth biological characterization performed by Dr Alizadeh at Stanford, is that for some sub-populations, such as patients who have non-GCB or ABC phenotype, consistently also what has been shown for polatuzumab in prior Phase I or Phase II single agent and combination trials, the benefit in terms of progression-free survival may be much higher, much higher than 7.5%, whereas there may be no much benefit for those who have GCB cell of origin. It makes sense, as we know that polatuzumab vedotin by targeting CD79B is very relevant to the B-cell receptor biology. Independently, though, from the cell of origin, those who have very high risk, large B-cell lymphoma with an IPI of four or five, may still maintain that benefit. In our practice, and this of course needs to be validated prospectively, we definitely like to select this regimen for patients who have non-GCB subtype with an IPI of two or higher or for those who have very high IPI independently from the cell of origin.

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