Parsaclisib Plus Obinutuzumab and Bendamustine Demonstrates Preliminary Efficacy, Safety for Patients With R/R Follicular Lymphoma

Results from the Phase 1 CITADEL-102 Trial

According to findings of the CITADEL-102 trial recently published in Hematological Oncology, the combination of parsaclisib, an oral, highly selective PI3Kδ inhibitor, plus obinutuzumab and bendamustine demonstrated promising preliminary efficacy and a manageable safety profile among patients with relapsed/refractory (R/R) follicular lymphoma (FL) who had been previously treated with rituximab-containing regimens. 

Mehdi Hamadani, MD, Medical College of Wisconsin, Milwaukee, Wisconsin, and coauthors stated that although anti-CD20-based chemotherapy regimens have been approved for first-line systemic treatment of FL, “many patients with advanced FL who respond to these regimens relapse, and each subsequent relapse is associated with shorter durations of response to following treatments.”

Parsaclisib has shown promise as monotherapy in improving clinical outcomes in patients with R/R FL who had received ≥2 prior systemic therapies. The present study aimed to assess the safety and efficacy of parsaclisib in combination with bendamustine and anti-CD20 antibody obinutuzumab among patients with R/R FL. The primary endpoint was the safety and tolerability of the treatment combination, and a secondary endpoint was objective response rate, including overall response rate, percentage of patients with a complete response or complete metabolic response and partial response, and complete response rate as determined by the Lugano Classification criteria for lymphoma. Other secondary endpoints included duration of response, progression-free survival, and overall survival. 

The phase 1 CITADEL-102 trial enrolled 26 patients with histologically confirmed CD20-positive R/R FL into 2 study parts. Part 1, the safety run-in, determined the maximum tolerated dose of parsaclisib to combine with standard doses of obinutuzumab and bendamustine. Part 2 was dose expansion with an open-label, single-group design and assessed the safety, tolerability, and efficacy of this regimen. 

All patients were administered parsaclisib at 20 mg once daily for 8 weeks, followed by 20 mg once weekly, in combination with standard dosages of obinutuzumab and bendamustine. In terms of efficacy, 65.4% of patients (n = 17) achieved a complete response, while 11.5% (n = 3) achieved a partial response, making the objective response rate 76.9%. 

The combination treatment demonstrated manageable safety, with 1 patient experiencing dose-limiting toxicity of grade 4 QT interval prolongation, deemed related to parsaclisib. 30.8% of patients (n = 8) discontinued treatment due to treatment-emergent adverse events . The most common were pyrexia (53.8%), neutropenia (50.0%), and diarrhea (46.2%). There were 2 cases of colitis (7.7%), and 1 case each of alanine aminotransferase and aspartate aminotransferase increase (3.8%), tonsil cancer (3.8%), and maculopapular rash (3.8%), which led to treatment discontinuation. 

In conclusion, Dr Hamadani et al stated that the treatment “did not result in unexpected safety events, with little evidence of synergistic toxicity, and demonstrated preliminary efficacy.” 

They added, “Further studies are required to establish the role of PI3K inhibitors in the management of patients with R/R FL.”

Source:

Hamadani M, Coleman M, Boccia R, et al. Safety and efficacy of parsaclisib in combination with obinutuzumab and bendamustine in patients with relapsed or refractory follicular lymphoma (CITADEL-102): a phase 1 study. Hematol Oncol. 2023; 1- 10. doi:10.1002/hon.3209