ASH 2024 | A Phase Ib study of venetoclax plus Pola-R-CHP in the frontline for patients with DLBCL

Hi, I’m Dr Catherine Diefenbach from the Perlmutter Cancer Center, and I’m here to talk to you today about some of the research that we’re presenting at the ASH annual meeting. So the first study I want to tell you about is a study for first-line BCL2 overexpressing diffuse large B-cell lymphoma, and this study combined the BCL2 inhibitor, venetoclax, with standard backbone of R-CHOP where polatuzumab has been substituted for vincristine, so R-CHP-POLA based on the POLARIX data. So this was R-CHP-POLA with venetoclax for patients who were overexpressing BCL2. They could also have a BCL2 translocation, and we took patients with translocations or overexpression of BCL6 and MYC as well, so both overexpressor and double and triple hit patients were included. All patients got six cycles of R-CHP-POLA plus venetoclax for five days in each cycle. Patients tolerated the therapy well and with this one year follow-up we saw no new safety signals. We had high response rates across the board and the exciting thing is particularly in this study that we had a hundred percent response rate in our double and triple hit patients which is really unusual as most of these patients are very insensitive to chemotherapy, and their response rate to standard R-CHOP is really suboptimal. So to see that this precision medicine approach resulted in 100% response rate, even in a small patient group, is really exciting. With one year of follow-up, we saw that the responses were quite durable, with an excellent progression-free survival and a median PFS that has not been reached. For our double and triple hit patients, which is the group that tends to have primary refractory disease or relapse early, what we found was that at one year of follow-up, there were two out of the seven patients who relapsed. Five patients did not relapse. Of those five, one died from COVID. So we have a one-year PFS of 66% in that patient population, which is extremely exciting as this is really an unmet need population. And I think the fact that we don’t have a two-year PFS follow-up in this study is a little bit disappointing. But I mean, I think particularly for patients with aggressive lymphoma, the one-year follow-up is a, you know, not perfect, but a good surrogate endpoint to show that we have durable responses. And this study is really a proof-of-concept study to show that particularly with later-generation BCL2 inhibitors, the combination, particularly for double and triple hit patients who have an unmet medical need is a rational combination that’s worthy of exploration.

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