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Clinical Trial
. 2023 Aug 22;7(16):4349-4357.
doi: 10.1182/bloodadvances.2022009168.

Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study

Li-Juan Deng  1 , Ke-Shu Zhou  2 , Li-Hong Liu  3 , Ming-Zhi Zhang  4 , Zhi-Ming Li  5 , Chun-Yan Ji  6 , Wei Xu  7 , Ting Liu  8 , Bing Xu  9 , Xin Wang  10 , Su-Jun Gao  11 , Hui-Lai Zhang  12 , Yu Hu  13 , Yan Li  14 , Ying Cheng  15 , Hai-Yan Yang  16 , Jun-Ning Cao  17 , Zun-Min Zhu  18 , Jian-Da Hu  19 , Wei Zhang  20 , Hong-Mei Jing  21 , Kai-Yang Ding  22 , Xiang-Yang Zhang  23 , Ren-Bin Zhao  23 , Bin Zhang  23 , Ya-Min Tian  23 , Yong-Ping Song  2 , Yu-Qin Song  1 , Jun Zhu  1
Affiliations
Clinical Trial

Orelabrutinib for the treatment of relapsed or refractory MCL: a phase 1/2, open-label, multicenter, single-arm study

Li-Juan Deng et al. Blood Adv. .

Abstract

Relapsed or refractory (r/r) mantle cell lymphoma (MCL) is an aggressive B-cell malignancy with a poor prognosis. Bruton tyrosine kinase (BTK) is a mediator of B-cell receptor signaling and is associated with the development of B-cell lymphomas. Patients with r/r MCL were enrolled in this phase 1/2 study and treated with orelabrutinib, a novel, highly selective BTK inhibitor. The median number of prior regimens was 2 (range, 1-4). The median age was 62 years (range, 37-73 years). Eligible patients received oral orelabrutinib 150 mg once daily (n = 86) or 100 mg twice daily (n = 20) until disease progression or unacceptable toxicity. A dose of 150 mg once daily was chosen as the preferred recommended phase 2 dose. After a median follow-up duration of 23.8 months, the overall response rate was 81.1%, with 27.4% achieving a complete response and 53.8% achieving a partial response. The median duration of response and progression-free survival were 22.9 and 22.0 months, respectively. The median overall survival (OS) was not reached, and the rate of OS at 24 months was 74.3%. Adverse events (AEs) occurring in >20% of patients were thrombocytopenia (34.0%), upper respiratory tract infection (27.4%), and neutropenia (24.5%). Grade ≥3 AEs were infrequent and most commonly included thrombocytopenia (13.2%), neutropenia (8.5%), and anemia (7.5%). Three patients discontinued treatment because of treatment-related adverse events (TRAEs), but no fatal TRAEs were reported. Orelabrutinib showed substantial efficacy and was well tolerated in patients with r/r MCL. This trial was registered at www.clinicaltrials.gov as #NCT03494179.

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Conflict of interest statement

Conflict-of-interest disclosure: X.-Y.Z., R.-B.Z., B.Z., and Y.-M.T. are employees of InnoCare Pharma Limited. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Best percentage change from baseline in the SPD of target lesions for all 106 patients treated with orelabrutinib.
Figure 2.
Figure 2.
Duration of response, progression-free survival, and overall survival in full analysis set population. (A) IRC-assessed DOR, (B) PFS, and (C) overall survival in full analysis set population. NR, not reached.
Figure 3.
Figure 3.
Duration of response, progression-free survival, and overall survival in patients achieving CR, PR, or who were non-responders (SD/PD). (A) IRC-assessed DOR, (B) PFS, and (C) overall survival.
Figure 4.
Figure 4.
Subgroup analysis of ORR assessed by the IRC based on baseline demographic and clinical characteristics.
See this image and copyright information in PMC

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