VIDEO: Approaching high-risk subtypes in DLBCL

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The highest risk subtype would be the double hit lymphoma patients, as we discussed. These patients, again, with the FISH translocation of C-MYC BCL2. In this discussion, obviously, it is just mentioned, typically we'll try to break apart large cell lymphoma into four cohorts: germinal center, non-germinal center, and then we look at non-germinal center with IHC expression of C-MYC and BCL2, which we consider to be double expressors, and then we have the double hits. The first two, generally I would just assume patients, and discuss with them, that they generally have a very good outcome, typically respond very well to treatment, especially like I say with the non-germinal center with the POLARIX data, that support maybe using that in that patient population. The double expressors are generally thought to be the bad actors in the non-germinal center EPOCH B-cell subtype. We don't have a lot of clinical trials, per se, that show a distinctive advantage of one thing over another with these double expressors.

I mean, so in this conversation, historically, before the approval of the POLARIX and R-CHP-pola, I would literally go over this sort of scenario with patients and say, "We expect that this will do worse. But, unfortunately, we don't have anything better to offer." I can't say for sure that R-CHP-pola would generate better outcomes, but that would likely be my treatment choice in this patient population to date. With the double hit patients, obviously we discussed just the very bad outcomes with double hit lymphoma, and the need to hopefully get a remission with initial therapy, because these patients tend to do very poorly with early relapse or refractory disease. We know historically these patients did not respond very well to salvage chemotherapy and an autologous stem cell transplant. There is some improvement with CAR T, but with CAR T, obviously, it's still not a slam dunk, because up to 50 to 60% of these patients won't respond to the CAR T product, and sort of put them on a very, sort of, unfortunate road, where we likely will not be able to cure these patients. So a lot of these patients, like I said, the discussion is had upfront, at least to give them some realistic expectation of my intent with the initial therapy.

For these ones with the sort of bad characteristics, obviously, just put it in perspective how they fare compared to those who don't have these, sort of, higher risk features, and, sort of, what we can expect with initial treatment, and, sort of, what happens if we don't necessarily have a good response to initial treatment. And, these two high-risk subsets that we discussed, the use of CAR T very early in these patients, and then thereafter, obviously, discussion of whatever we have left, which is likely just bispecifics, and other sort of targeted treatments. But, just making them aware that more than likely if we don't necessarily get a remission the first time, very unlikely to get a remission with subsequent lines of therapy, even though CAR T has, sort of, improved that outcome a bit, compared to historical results.