CITADEL-205: Durable Response to Parsaclisib in Relapsed/Refractory MCL

In the phase II CITADEL-205 study, roughly two-thirds of patients with relapsed/refractory and Bruton tyrosine kinase (BTK) inhibitor–naïve mantle cell lymphoma (MCL) responded to parsaclisib monotherapy. These findings were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.

CITADEL-205: Parsaclisib for MCL

Parsaclisib is an oral phosphatidylinositol 3-kinase (PI3K) inhibitor. In the open-label CITADEL-205 study, parsaclisib was evaluated in a cohort of adults with relapsed/refractory MCL with documented cyclin D1 overexpression or t(11;14) translocation and an Eastern Cooperative Oncology Group performance status of at least 2. Eligible patients had received one to three previous lines of systemic therapies, with no history of BTK or PI3K inhibitor use.

In total, 108 patients received an initial regimen of parsaclisib 20 mg once daily for eight weeks, followed by parsaclisib at either 20 mg weekly (n = 31) or 2.5 mg daily (n = 77). Participants’ median age was 72 years and around 80% of patients were male. The primary endpoint was objective response rate (ORR) and secondary endpoints included complete response (CR) rates, duration of response (DOR) overall survival (OS), progression-free survival (PFS), safety, and tolerability.

Treatment Response and Safety Profile

In the overall cohort, 72.2% of patients (n = 78) had discontinued parsaclisib as of data cut-off, after a median treatment duration of 8.3 months. Discontinuation was primarily due to progressive disease (45.5%) and adverse events (AEs; 23.1%). Median follow-up from first dose for the entire cohort was 22.9 months. In the daily-dosing group, median treatment duration was 7.9 months.

In the overall cohort, the ORR was 68.5%. In the daily-dosing group, ORR was 70.1%, while ORR was 64.5% in the weekly-dosing group. Twelve patients in the daily-dosing group achieved a CR, compared to seven patients in the weekly group (15.6% vs. 22.6%). Rates of partial response were 54.5% in the daily-dosing group and 41.9% in the weekly-dosing group.

Among all patients who responded to parsaclisib, 89.2% had responded by first disease assessment, suggesting a rapid onset of response. The median DOR was 13.7 months overall, and 12.1 months in the daily-dosing group specifically. The median PFS was 11.99 months in the overall cohort, and 13.6 months in the daily-dosing group. At cut-off, median OS had not been reached in the study population.

Treatment-emergent AEs were common, the authors noted, and were reported in 90.7% of patients. These AEs were grade ≥3 in 62.0% of patients. The most common AEs were diarrhea (any-grade, 34.3%; grade ≥3, 13.9%), pyrexia (17.6%), and constipation (13.0%). Grade ≥3 neutropenia occurred in 8.3%. Nearly half of patients required dose interruptions due to treatment-emergent AEs and 8.3% required dose reductions. Six patients (5.6%) experienced fatal treatment-emergent AEs.

“Parsaclisib monotherapy demonstrated a rapid and durable response, had an acceptable safety profile, and was generally well tolerated in BTK inhibitor–naive patients with relapsed/refractory MCL,” the authors concluded. “These data suggest that parsaclisib could be a potential treatment option for patients with relapsed/refractory MCL.”