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EHA 2024 | The real-world comparative effectiveness of covalent BTKis in R/R MCL
Tycel Phillips, MD, City of Hope, Duarte, CA, discusses the real-world comparative effectiveness of covalent BTK inhibitors (BTKis) among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). While the efficacy of these BTKis has traditionally been considered equivalent, second-generation BTKis acalabrutinib and zanubrutinib show an improved toxicity profile compared to the first-generation ibrutinib. Real-world data indicate that zanubrutinib improves overall response rate (ORR) and duration of response (DOR) compared to ibrutinib, possibly due to fewer treatment discontinuations from toxicity. This interview took place at the 29th Congress of the European Hematology Association (EHA) in Madrid, Spain.
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Transcript
Historically, we had three covalent BTK inhibitors improved. There was a ibrutinib, acalabrutinib, and zanubrutinib. More recently, ibrutinib has lost its approval in indication within the United States, but is still available worldwide. As a whole, efficacy of these three covalent BTK inhibitors has always been presumed to be equivalent. Obviously, the difference being of these drugs, ibrutinib being the first generation, acalabrutinib and zanubrutinib being second generation drugs, has been in the toxicity profiles, with the two second generation drugs having an improved toxicity profile as compared to ibrutinib...
Historically, we had three covalent BTK inhibitors improved. There was a ibrutinib, acalabrutinib, and zanubrutinib. More recently, ibrutinib has lost its approval in indication within the United States, but is still available worldwide. As a whole, efficacy of these three covalent BTK inhibitors has always been presumed to be equivalent. Obviously, the difference being of these drugs, ibrutinib being the first generation, acalabrutinib and zanubrutinib being second generation drugs, has been in the toxicity profiles, with the two second generation drugs having an improved toxicity profile as compared to ibrutinib.
And so what we took in this situation is look at a real world data set to try to compare sort of time to start efficacy of some of these covalent BTK inhibitors. Surprisingly, what we saw was that it did appear to be an improvement in overall response rate and duration of response with zanubrutinib versus ibrutinib. Some of this could be confounding because of the situation with ibrutinib because of toxicity, sometimes patients will stop, start or be discontinued on this medication and switch to another medication. So that could account for some of the differences. And there was a hint of a trend toward a benefit between acalabrutinib and zanubrutinib. But that wholeheartedly was probably explained by the low numbers of patients in the zanubrutinib arm as compared to what we saw with acalabrutinib as a whole. Because, again, there is no real rational reason to necessarily notice a difference between these two sort of classes of second generation covalent BTK inhibitor drugs.
As we move along and get more real world data sets and more real world information, we will be able to tease out some subtle differences between the two drugs. But as a whole, from what we’ve discovered, is that again, because of the sort of complex picture and what we take as a whole, Zanubrutinib appears to be probably a better BTK inhibitor than ibrutinib mainly, I suspect, because of toxicity and sort of discontinuations. And it seems to be, again, as we suspect it, to be equivalent as a second generation BTK inhibitor to acalabrutinib in this patient population.
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