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Parsaclisib Monotherapy Well Tolerated in Patients With R/R MCL
Parsaclisib monotherapy showed rapid and durable response, an acceptable safety profile, and was generally well tolerated in BTK inhibitor-naïve patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL); these data were presented at the 2021 American Society of Hematology (ASH) Annual Meeting.
MCL is an aggressive type of non-Hodgkin lymphoma (NHL) and accounts for approximately 6% of all NHL cases in Western countries (Thandra KC. Med Sci. 2021;9:5). Available first line treatment options are not curative and most patients relapse (Wu H. Front Oncol. 2020:10:588314; Kumar A. Blood Cancer J. 2019;9:50). Second line and later lines of therapy are mostly targeted, such as Bruton’s tyrosine kinase (BTK) inhibitors, however treatment intolerances, failure, and poor survival outcomes are common (Epperla N. Hematol Oncol. 2017;35:528–35; Jain P. Br J Haematol. 2018;182:404–11).
With more novel therapies necessary for patients with R/R MCL, Amitkumar Mehta, MD, UAB School of Medicine, Birmingham, Alabama, and co-investigators, reported on the results of the open-label, phase 2 CITADEL-205 study on parsaclisib in BTK inhibitor-naïve patients with R/R MCL.
Patients who were ≥18 years old, had pathologically confirmed MCL with documented cyclin D1 overexpression or t(11;14) translocation, an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2, received 1 to 3 prior systemic therapies, and not had any prior treatment with a BTK and/or PI3K inhibitor, were enrolled in the study.
In all, 108 patients received parsaclisib 20mg once daily for 8 weeks followed by either 20 mg once weekly (WG, n=31) or 2.5 mg once daily (DG, n=77).
The primary endpoint was objective response rate (ORR) as determined by an independent review committee (IRC). The secondary endpoints included complete response rate (CRR), duration of response (DOR), overall survival (OS), progression-free survival (PFS), and safety and tolerability.
As of the data cutoff of January 15, 2021, the median age was 72 years, 92.6 percent had ECOG PS ≤ 1, and the median time from initial diagnosis was 3.6 years. Among all patients, 63.9 received 1 line and 25.9 percent received 2 lines of prior systemic therapy; 31.5 percent had prior hematopoietic stem cell transplant; 50 percent had relapsed; and 43.5 percent were refractory to their most recent therapy.
The “median treatment duration and follow-up from first dose to data cutoff were 8.3 months and 22.9 months for all patients, and 7.9 and 18.2 months for DG, respectively,” continued Dr Mehta and co-investigators.
The ORR was 58.5 percent (95% CI, 58.9-77.1) for all patients, and 70.1 percent (58.6-80) for DG. The CRR was 17.6 percent (10.9-26.1) for all patients and 15.6 percent (8.3-25.6) for DG. Among all patients with complete or partial response, 89.2 percent of responses occurred at the first disease assessment. The median DOR was 13.7 months for all patients and 12.1 months for the DG. The median PFS was 11.99 months and 13.6 months, respectively. The median OS was not met.
Treatment was halted by 78 patients (72.2%), primarily due to progressive disease in 49 (45.4%) and adverse events (AEs) in 25 (23.1%). Among all patients, treatment-emergent AEs (TEAEs) happened in 90.7 percent (n=98) patients, and grade ≥3 TEAEs occured in 62 percent (n=67). The most common TEAEs were diarrhea (34.3%), pyrexia (17.6%), and constipation (13%), and the most common grade ≥3 TEAEs included diarrhea (13.9%) and neutropenia (8.3%). TEAEs led to dose interruptions and reductions in 47.2 percent and 8.3 percent of all patients, respectively. They also led to treatment discontinuation in 25 percent of all patients, the most common being diarrhea (11.1%), colitis (4.6%), and hypokalemia (2.8%). Serious TEAEs were noted in 42.6 percent (n=46) of all patients, the most common being diarrhea (9.3%) and colitis (4.6%). Six patients (5.6%) had a fatal TEAE.
“Parsaclisib monotherapy demonstrated a rapid and durable response, had an acceptable safety profile, and was generally well tolerated in BTK inhibitor–naive pts with R/R MCL. These data suggest that parsaclisib could be a potential treatment option for pts with R/R MCL,” concluded Dr Mehta and co-investigators.—Emily Bader
Mehta A, Trněný M, Walewski J, et al. Efficacy and safety of parsaclisib in patients with relapsed or refractory mantle cell lymphoma not previously treated with a BTK inhibitor: Primary analysis from a phase 2 study (CITADEL-205). Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 382.
