ASH 2024 | The predictive value of cell-of-origin subtype in patients with DLBCL receiving polatuzumab vedotin

We looked at 740 patients with large B-cell lymphoma who received polatuzumab vedotin, an antibody drug conjugate targeting CD79. And people will know the POLARIX study, a randomized Phase III trial in upfront DLBCL that found that patients with ABC type DLBCL had better responses to polatuzumab-containing regimens or Pola-R-CHP than patients with GCB type DLBCL. But of course POLARIX used gene expression profiling to separate these two subtypes of DLBCL and in the real world most people only have access to immunohistochemistry they don’t have access to real-time gene expression profiling. So we conducted a retrospective multi-center observational study with two main aims the first aim was to use Hans’ algorithm immunohistochemistry to separate patients into GCB and non-GCB type DLBCL and to see if this same differential effect differential response to polatuzumab was seen when we used Hans’ algorithm. And the second main aim of the study was to look in the relapsed/refractory setting because previously there’s only been three small observational studies and we wanted to conduct a appropriately powered study in the relapsed/refractory setting because clinicians still use a lot of polatuzumab in the relapse refractory setting particularly as bridging to CAR T-cell therapy. And so we collected data across the US from multiple different centers on 740 patients with large B-cell lymphoma and our primary endpoint was looking at overall response rate in the relapse refractory setting and indeed the primary endpoint was positive finding a higher overall response rate of about 57% in non-GCB patients with relapsed/refractory large B cell lymphoma compared to about 37% in patients with GCB type relapsed/refractory large B cell lymphoma and indeed there was also an increased progression-free survival in the relapsed/refractory cohort. If we move to look at the frontline cohort of about 100 patients in each arm, we found that there was no difference in response rate and no difference in progression-free survival. And at first glance, you might think that, oh, well, that’s a negative study. But in fact, you have to remember that there was no R-CHOP arm in our study. Everyone received polatuzumab. And we know that historically, patients with ABC type DLBCL do worse with R-CHOP than those with GCB and so we think, we hypothesize that maybe the polatuzumab is overcoming that previous adverse prognostic impact of the ABC type DLBCL and so we would encourage clinicians to factor cell of origin by Hans’ algorithm into their decision making about when to include polatuzumab and when to choose polatuzumab for their patients.

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