Abstract
Peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) are aggressive malignancies with limited effective treatment options in the relapsed or refractory (r/r) setting. Although targeting the PI3K pathway has shown potential by modulating T-cell signaling and eliciting antitumor activity, clinical application has been limited by significant immune-related toxicities. Linperlisib, a next-generation PI3Kδ inhibitor characterized by high potency and selectivity, with a reduced incidence of off-target toxicities compared to earlier compounds, is approved in China for follicular lymphoma, has demonstrated encouraging efficacy in Chinese patients with r/r PTCL, as evidenced by results from the open-label Phase II trial (NCT05274997) presented last year. Here, we report our single-center experience with linperlisib, including patients enrolled in the clinical trial as well as those who continued therapy through compassionate use as single patient IND.
Aims: To evaluate the clinical benefit, safety, and durability of responses to linperlisib in a single center cohort of r/r PTCL and CTCL patients, and to examine outcomes with a step-down maintenance dosing strategy . Pts received linperlisib 80mg QD for four 28-day cycles or achieved a complete response (CR) prior to a prespecified reduction to a 40mg QD continuous maintenance dose.
Method: We did analysis of 18 adults with r/r T-cell lymphomas (PTCL-NOS n=8, AITL n=8, ALCL n=1, CTCL n=1) treated at MD Anderson Cancer Center (Aug 2022–May 2025). Patients received therapy either through an open-label Phase II clinical trial (NCT05274997) or via compassionate use under single-patient IND protocols. Patients received linperlisib 80 mg QD for four 28-day cycles or until complete response (CR), followed by 40 mg QD maintenance. Tumor response was assessed every 2 treatment cycles per Lugano 2014 ( for PTCL) or Olsen criteria (for CTCL). Primary endpoint was investigator-assessed objective response rate (ORR). Pts with CR were eligible to proceed to consolidative transplant, if warranted by investigator review. Adverse events (AEs) were graded by CTCAE v5.0.
Results: The median patient age was 64 years with males (9) and females (9) ratio 1:1. ECOG 0 (50%) or 1 (50%), Caucasian 11 (61.1%), Black 6 (33.7%), or Hispanic 1 (5.6%). Patients had a median of 3 prior systemic therapies (range 1–7). ORR was 66% (CR 39%; PR 28%), with highest responses observed in AITL (ORR 75%). Responses most frequently occurred by the first assessment during the 80mg QD dose period. Median progression-free survival (mPFS) in the cohort was median PFS is 6.1 months (95% CI: 4.0 to 8.5 months), with a median overall survival (mOS) 29.7 months, (95% CI 22.4 to 37.1 months). Median response duration not reached. Among AITL cases, mPFS reached 6.25 months (95% CI 0, 18.9 months).
Two of the PTCL pts with CR subsequently received transplant and were censored from the PFS analysis. one CTCL pts achieved a PR and 4 pts had SD and further had PR, later progressed.
Adverse events (AEs) were predominantly mild to moderate. Grade 1–2 events included maculopapular rash (55.6%), diarrhea (50.0%), CMV reactivation (11.1%), nausea (22.2%), paresthesia (22.2%), constipation (16.7%), and peripheral neuropathy (11.1%). Severe AEs (Grade ≥3) affected 9 of 18 patients (50.0%), with lung infection being the most frequent (22.2%). Additional Grade 3 events included diarrhea (11.1%), colitis (5.6%), pancreatitis (5.6%), chest pain (5.6%), and peripheral motor neuropathy (5.6%).
Fourteen patients discontinued due to progression; three (on compassionate use) remain in remission at analysis cutoff. One patient who proceeded to allogeneic stem cell transplantation died from transplant-related complications.
Conclusions: In a heavily pretreated, with r/r PTCL/CTCL, linperlisib demonstrated robust activity with early and durable responses—especially in AITL—and a manageable safety profile, including with step-down dosing. These findings support further exploration of Linperlisib in US population and use of maintenance dosing strategy. Overall the safety profile was manageable, and treatment-related AEs were generally reversible or non-life-threatening.
