The second abstract I presented is on pirtobrutinib in relapsed/refractory mantle cell lymphoma. Among 90 primary analysis patients with relapsed mantle cell lymphoma, the overall response rate was 58% and CR was very reasonable.
What is astonishing is that in BTK-naive patients, those with mantle cell lymphoma relapse, never received a prior covalent BTK inhibitor, the response rate among 15 patients was 85%...
The second abstract I presented is on pirtobrutinib in relapsed/refractory mantle cell lymphoma. Among 90 primary analysis patients with relapsed mantle cell lymphoma, the overall response rate was 58% and CR was very reasonable.
What is astonishing is that in BTK-naive patients, those with mantle cell lymphoma relapse, never received a prior covalent BTK inhibitor, the response rate among 15 patients was 85%. So, let me explain the significance of this: all the FDA approved covalent irreversible BTK binders and inhibitors, they cause around a similar overall response rate between 70 to 90%, the CR is about half of that, maybe a little more. But, because the three agents bind to the same epitope on the ATP binding site of the Bruton’s tyrosine kinase protein, and so if the patient is treated with one covalent BTK inhibitor and becomes resistant, this same patient will be resistant to the other two.
As we all know, the three approved agents, covalent BTK inhibitors include ibrutinib, acalabrutinib, and zanubrutinib. But pirtobrutinib binds very differently from the three covalent BTK inhibitors: it binds to the BTK protein also in the HP binding site, but in a non-covalent, reversible fashion. So even new proteins, new BTK proteins, are made, and because it’s constantly binding on and off, it can inhibit the newly formed BTK proteins. So this way, the effect of pirtobrutinib is very impressive and it can overcome prior covalent BTK inhibitor resistance and it is even more effective in prior BTK now exposed to patients with mantle cell lymphoma.