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1677 PI3Kδ Inhibitor Linperlisib As a ≥ 3-Line Treatment for Relapsed or Refractory Follicular Lymphoma: A Subgroup Analysis of a Phase II, Single-Arm, Open-Label Trial

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, health outcomes research
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Hang Su1*, Tingyu Wang2*, Xiuhua Sun3*, Lihua Qiu4*, Junning Cao5, Zhiming Li6*, Yuqin Song, MD7, Li Zhang8*, Dengju Li9*, Huijing Wu, MD10*, Wei Zhang11*, Junmin Li12*, Keshu Zhou, MD13*, Hui Zhou14*, Yu Yang15*, Zhifeng Li16*, Hong Cen17*, Zhen Cai18*, Zhihui Zhang, MD19*, Weijun Fu20*, Jie Jin IV21*, Fei Li22*, Weixin Wu23*, Xuekui Gu24*, Weiliang Zhu25*, Lihong Liu26*, Zengjun Li27*, Shuhua Yi28*, Hanying Bao29*, Zusheng Xu29* and Lugui Qiu2

1307 Hospital Affiliated To the Academy of Military Medical Sciences, Beijing, China
2State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology& Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
3The Second Hospital of Dalian Medical University, Dalian, China
4Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
5Department of Lymphoma, Fudan University Shanghai Cancer Center, Shanghai, China
6Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
7Department of Lymphoma, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, BEIJING, China
8West China Hospital, Sichuan University, Chengdu, China
9Department of Hematology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
10Hubei Cancer Hospital, Wuhan, China
11Chinese Academy of Medical Sciences & Peking Union Medical College, Department of Hematology, Beijing, China
12Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
13Department of Hematology, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
14Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
15Fujian Provincial Cancer Hospital, The Affiliated Tumor Hospital of Fujian Medical University, Fuzhou, China
16Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Xiamen, China
17Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
18Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
19Sichuan Cancer Hospital and Institute, Chengdu, China
20Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
21The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
22The First Affiliated Hospital of Nanchang University, Nanchang, China
23Zhongshan Hospital, Xiamen University, Xiamen, China
24Department of Hematology, , The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
25Zhujiang Hospital of Southern Medical University, Guangzhou, China
26The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
27State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical Colleg, Tianjin, China
28Tianjin Institutes of Health Science, Tianjin, China
29Shanghai Yingli Pharmaceutical Co., Ltd., Shanghai, China


Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma (NHL), originating in follicular central B cells, and accounts for approximately 22% of all newly diagnosed cases of NHL. Chemo-immunotherapy is the standard treatment option for FL. Unfortunately, the progression of the disease to relapsed or refractory FL (r/r FL) is still inevitable, which raised concern about subsequent effective treatments. Several δ isoform of phosphatidylinositol 3-kinase (PI3K-δ) inhibitors have ever been approved for r/r FL after ≥2 lines of prior therapies. However, most of their indications for r/r FL were withdrawal for increased risk of death and serious side effects. The latest data from the Chinese phase II clinical trial of linperlisib (Trial registration ID: NCT04370405), a novel oral PI3Kδ-selective inhibitor, in patients with r/r FL who had received at least two systemic therapies were presented. In this trial, linperlisib demonstrated compelling efficacy and was generally well-tolerated in the treatment of r/r FL patients after ≥2 prior systemic therapies. Linperlisib was approved by China National Medical Products Administration (NMPA) for adult r/r FL previously treated with at least two system therapies in November 2022. The ≥3 lines of treatment options are still unmet for the r/r FL. In this setting, this subgroup analysis of the linperlisib phase II trial aimed to evaluate outcomes of linperlisib in later-line treatment of r/r FL.


This study included all the patients with r/r FL who had received at least two systemic therapies previously enrolled in the open-label, single-arm, phase II trial (linperlisib, 80mg, po, q.d., in a 28-day cycle), with overall response rate (ORR) as the primary endpoint. In this subgroup analysis, the patients were divided into two groups according to the treatment lines they received: >3 prior lines of treatment and ≤3 prior lines of treatment. All of the statistical analyses were descriptive.


A total of 84 r/r FL patients from 25 sites in China from April 2019 to September 2020 were enrolled in this trial, with a cutoff date of September 30, 2021. The ORR was 79.8%, with statistical significance in a heavily pretreated FL patient population with a median of 4 prior therapies, with a well-tolerated safety profile. A total of 43 patients received >3 prior lines of treatment, while 41 patients received ≤3 prior lines of treatment.

The median age between the two groups was similar (range: 29.0 – 78.0, 52.0 years for >3 prior lines vs. 48.0 years for ≤3 prior lines). The majority of patients had Ann Arbor staging III-IV (40 for >3 prior lines vs. 34 for ≤3 prior lines). The median number of prior regimens was 4 for >3 prior lines and 3 for ≤3 prior lines.

Overall, there were 67 patients achieved responses, with ORR of 83.7% (36, 95%CI:69.3, 93.2) for >3 prior lines vs. 75.6% (31, 95% CI: 59.7, 87.6) for ≤3 prior lines based on independent review committee assessment. Compared with patients who received ≤3 prior lines, patients received ≤3 prior lines achieved higher disease control rate (41[95.3] vs. 37 [90.2%]). The median DOR was 12 months (95% CI: 7.3, 15.9) for >3 prior lines vs. 13 months (95% CI: 9.2, NE). The median PFS was 11.9 months (95% CI: 9.1,19.4) for >3 prior lines vs. 13.3 months (95% CI: 8.2, NE) for ≤3 prior lines. The OS of both groups was not reached.

The most common treatment-related adverse events (≥20%, TRAEs) were neutropenia (21 [48.8%] for >3 prior lines vs. 18 [43.9%] for ≤3 prior lines), leukocyte count decreased (15 [34.9%] vs. 15 [36.6%]), alanine aminotransferase increased (10 [23.3%] vs. 9 [22.0%]), lymphocyte count decreased (9 [20.9%] vs. 5 [12.2%]), hypertriglyceridemia (9 [20.9%] vs. 11 [26.8%]), and hypercholesteremia (6 [24.0%] vs. 7 [11.9%]). The most common grade ≥3 TRAEs (≥10%) were neutropenia (9 [20.9%] vs. 4 [9.8%]), pulmonary inflammation (3 [7.0%] vs. 6 [14.6%]), infectious pneumonia (2 [4.7%] vs. 5 [12.2%]).


This subgroup analysis revealed that linperlisib could achieve benefit in r/r FL patients who received at least 2 prior system therapies regardless of treatment lines. The AEs were well-tolerated. Further trials with large-scale samples were warranted.

Disclosures: Fu: Shanghai Changzheng Hospital: Other: WJF is a former staff of Shanghai Changzheng Hospital and now is a staff of Shanghai Fourth People's Hospital affiliated to Tongji University. ; Takeda Pharmaceutical Company Limited.: Research Funding.

*signifies non-member of ASH