Amitkumar Mehta, MD, UAB School of Medicine, Birmingham, AL, reports findings from the Phase II CITADEL-205 trial (NCT03235544) of parsaclisib, a phosphatidylinositol 3-kinase (PI3K) δ inhibitor, in patients with mantle cell lymphoma (MCL). Patients were initially stratified based on whether they were pre-treated with Bruton’s tyrosine kinase (BTK) inhibitors, but the arm containing pre-treated patients ceased treatment due to low efficacy. The 108 remaining patients received either a weekly or daily dose of parsaclisib and a promising objective response rate (ORR) and progression-free survival (PFS) were observed. An encouraging safety profile was additionally reported, with no grade 4 transaminitis occurring. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.
Transcript (edited for clarity)
The CITADEL-205 is a study of parsaclisib, which is a highly specific PI3Kδ inhibitor in mantle cell lymphoma. So in this meeting, parsaclisib activity in follicular, marginal, as well as mantle cell lymphoma was presented. I presented data on mantle cell lymphoma. It was a very interesting study in adult patients with mantle cell lymphoma who have at least seen one line of therapy. They were enrolled...
The CITADEL-205 is a study of parsaclisib, which is a highly specific PI3Kδ inhibitor in mantle cell lymphoma. So in this meeting, parsaclisib activity in follicular, marginal, as well as mantle cell lymphoma was presented. I presented data on mantle cell lymphoma. It was a very interesting study in adult patients with mantle cell lymphoma who have at least seen one line of therapy. They were enrolled. Initially the study had two arms, those patients who were BTK-naive, and those patients who had been exposed to BTK inhibitors, those were enrolled. But the arm with those patients who have been exposed to BTK inhibitors was terminated early because we saw not great activity of parsaclisib in this patients setting. That was presented in last ASH meeting. This ASH meeting, we focused on patients who have not been exposed to BTK inhibitors. So about 108 patients were enrolled and the majority of the patients were in daily group.
So we divided the patient into two groups: weekly and daily group. So the weekly group is those patients after eight weeks or 20 milligram of parsaclisib, they were so to speak on a maintenance dose of 20 milligram, weekly, or after eight weeks of 20 milligram, daily dose to 2.5 milligram daily dose. So those were the two arms. And after an interim analysis, we switched all the patients to daily group. So the data were presented at a total group or a daily group. And about 77 patients were enrolled in a daily group, in total 108 patients. And as you can see the response rate in this patient population is very impressive. About 70% and 20% complete response rate. Impressively also most of the patients responded within a month or two of starting parsaclisib.
Most of the patients [inaudible] The major side effect that we saw in this patient population was diarrhea or colitis and neutropenia. The PI3Kδ inhibitor parsaclisib is designed to avoid transaminitis and in our patient population, we did not see any grade 4 transaminitis. So that was kind of the whole goal of parsaclisib, to avoid transaminitis. The duration of response, as well as progression-free survival was impressive, about a year or a little bit more than a year in daily group. So parsaclisib now is another option for mantle cell lymphoma. As we all know that in mantle cell lymphoma, BTK inhibitors are kind of a backbone for the treatment. Parsaclisib offers similar activity with a different toxicity profile. We know that like ibrutinib and others, they have side effect and in a real-world population, many of the patients, they discontinue BTK inhibitors because of intolerance. So parsaclisib offers another option for those patients.