Tycel J. Phillips, MD from Rogel Cancer Center, University of Michigan discusses the ASH 2020 abstract – 338 Phase 2 Study Evaluating the Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Marginal Zone Lymphoma (CITADEL-204).
Context:
Clinically heterogeneous, indolent, non-Hodgkin lymphoma (NHL) is a marginal zone lymphoma (MZL) with 3 subtypes known as extranodal, nodal, and splenic MZL. In a phase 1/2 study in patients with previously treated B-cell malignancies, Parsaclisib, an active, highly-selective, next-generation phosphatidylinositol 3 kinase (PI3K) δ inhibitor, has shown promising response rates. In patients with relapsed or refractory (R/R) MZL, CITADEL-204 (NCT03144674) is a multicenter, open-label phase 2 analysis of parsaclisib. Preliminary findings for patients not previously treated with Bruton’s Tyrosine Kinase Inhibitor (BTKi-naïve) are published here.
Methodology:
Almost 18 years of age with histologically confirmed MZL were qualifying patients who received around 1 prior systemic therapy line, including anti-CD20 therapy, but were BTKi-naïve. Patients indicated worsening of disease or lack of response to the most recent regimen, radiologically observable lymphadenopathy, or extranodal lymphoid malignancy (or histologically documented infiltration of the bone marrow in cases of splenic MZL), and performance status of the Eastern Cooperative Oncology Community (ECOG PS) ⇠2. It was important to have prophylaxis for Pneumocystis jirovecii pneumonia (PJP).
Patients were assigned to receive 20 mg once daily (QD) of parsaclisib for 8 weeks followed by either 20 mg once weekly (weekly dose group [WG]) or 2,5 mg QD for 8 weeks (daily-dosing group [DG]). The primary endpoint was objective response rate (ORR); the secondary endpoints were full response rate (CRR), response period (DOR), progression-free survival (PFS), overall survival (OS), and protection and tolerability. An independent evaluation committee evaluated all radiology-based endpoints (IRC). Protection was assessed in all treated patients, and efficacy was assessed in all treated patients who had a follow-up duration of ⇠9 weeks, had at least 1 post-baseline examination, or prematurely discontinued participation in the research.
Outcomes:
99 patients (WG, n = 28; DG, n = 71) were treated from December 2017 through January 17, 2020 (data cut-off). The median age was 71 years; 52.5% of the patients were male, 94.9% had ECOG PS alone and 31.3%, 33.3%, and 35.4% had nodal, extranodal, and splenic MZL, respectively. 2 was the median number of past systemic therapies. At cut-off, 40 (40.4 percent) patients, including 20 (20.2 percent) for disease progression, had discontinued care. Median exposure (range) to parsaclisib was 7.5 months (0.4−22.4).
At the data cut-off, 94 patients, including 66 in DG, were evaluable for response (Table). Median (range) follow-up for the efficacy evaluable population was 11.1 months (1.2−25.0) overall and 9.5 months (1.2−25.0) in DG. The ORR (95 percent confidence interval [CI]) was 54.3 percent (43.7-64.6) overall and 57.6 percent (44.8-69.7) in DG; for patients with nodal, extranodal, and splenic MZL, the ORR (95 percent CI) was 48.3 percent (29.4-67.5), 50.0 percent (31.9-68.1), and 63.6 percent (45.1-79.6) respectively (Table). The median response time was 8 weeks. The median DOR (95 percent CI) among all respondents was 9.3 months (6.2-not evaluable [NE]) and 9.4 months (6.0-NE) in DG. Overall, the median PFS (95% CI) was 13.8 months (8.8−NE) and 11.5 months (8.3-NE) in DG.
The most common treatment-emergent AEs (TEAEs) among the 99 patients treated were diarrhea (36.4 percent of patients), cough (18.2 percent), and rash (14.1 percent ). Neutropenia and diarrhea were the most popular grade-3 TEAEs (8.1 percent, each). Febrile neutropenia and pneumonia, the most popular severe TEAEs, were (5.1 percent, each). TEAEs leading to dose interruption or dose reduction occurred in 47.5% and 14.1%, respectively, of patients. In 15.2% of patients, TEAEs leading to discontinuation occurred; diarrhea (5.1 percent) and colitis were the most common cases (3.0 percent ). Four patients with 2 cases, febrile neutropenia (n = 1) and sepsis (n = 1), considered to be linked to treatment, had TEAEs leading to death. Increases in alanine/aspartate amino transferase (2.0 percent/1.0 percent of patients) and decreases in neutrophil count (13.1 percent), platelet count (3.0 percent), and hemoglobinin were included in new or deteriorating grade 3 laboratory test values of clinical significance (3.0 percent ).
The Conclusion:
Rapid and durable responses with single-agent parsaclisib were achieved by BTKi-naïve patients with R/R MZL. In patients diagnosed with nodal, extranodal, or splenic MZL, comparable efficacy was observed. Without unforeseen toxicities, treatment with parsaclisib was usually well tolerated. It will present updated data.