ASH 2020 | CITADEL-205: parsaclisib for R/R MCL

CITADEL-205 is a phase II study of parsaclisib, which is a highly specific PI3-delta inhibitor in patients with relapsed/refractory mantle cell lymphoma who have not been exposed to BTK inhibitor. Parsaclisib is like many other PI3-delta inhibitor, but it is very highly specific and it was designed to reduce the liver toxicities that were seen with other delta inhibitors and it does not impact much alpha or gamma subtype. It’s mainly focused on delta inhibition. These patients, we enrolled 108 patients on the study and we divided these patients into two groups. One group was weekly group and the other group was daily group. And one of the reason was we wanted to evaluate whether there is any impact on the efficacy and the side effect, especially the diarrhea.

The weekly group patients, they initially, both groups, actually, they got for eight weeks, they got daily 20 milligrams of parsaclisib and, after eight weeks, the patients were randomized as a weekly group when they get 20 milligrams every week or daily group where they get a lower dose, 2.5 milligrams daily. The patients were allowed to cross over to the daily group, and we decided they will continue with the daily group. So that’s why we have about 31 patients who were in both groups, who were on daily group, then they were crossed over to the weekly group to daily group. And we enrolled 108 patients on that, and that’s the data that we reported. The primary inclusion or eligibility criteria for those patients were they’re adult patients with relapsed/refractory mantle cell lymphoma who have not been exposed to any BTK inhibitor, that is ibrutinib or acalabrutinib. We have other abstract, which Dr. Zinzani presented, 2044, where the patients were allowed who were exposed to BTK inhibitor. So that was a part of the study, but we reported both the results differently.

The primary end point of the study was overall response rate. And the secondary end point of the study was exploring progression free survival, duration of response, and the toxicity profile of parsaclisib, and there were a few others. Overall, we noted that the response rate were very impressive, both by IRC, as well as the investigator assessment. We saw a 70 to 71% response rate or response rate with about 15% patient going in complete remission with this agent. So, the evaluation was mainly by the CT scans based on a Lugano 2014 criterias.

Impressively, also, in the weekly group, the duration of response was nine months and median progression free survival was about a year. The toxicity profile was much better, compared to other delta inhibitor. Still, we saw diarrhea and colitis as the top side effect of this agent. And that was one of the reasons that we wanted to change our strategy after eight weeks. On an average, the onset of diarrhea was four months. And if you detect it early and hold the agent and treat it, then on an average, about 10 days, it got resolved to less than grade two. So, overall, the safety profile was tolerable. Apart from diarrhea and colitis, we also seen neutropenia, but, otherwise, it was well handled agent.

So, in a way, we saw that this is a good option for patients who are intolerant or not exposed to BTK inhibitor. If there is a contraindication to go on ibrutinib or acalabrutinib, like atrial fibrillation or cardiovascular toxicities, and you know, they cannot go on a BTK inhibitor, then they can have a good option of PI3 kinase delta inhibitor.