Safety and antitumor activity of acalabrutinib for relapsed/refractory B‐cell malignancies: A Japanese phase I study

Izutsu, Koji; Ando, Kiyoshi; Ennishi, Daisuke; Shibayama, Hirohiko; Suzumiya, Junji; Yamamoto, Kazuhito; Ichikawa, Satoshi; Katô, Kôji; Kumagai, Kyoya; Patel, Priti; Iizumi, Sakura; Hayashi, Nobuya; Kawasumi, Hisashi; Murayama, Kazuro; Nagai, Hirokazu

doi:10.1111/cas.14886

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…Rash, diarrhea, headache, nausea, fatigue, and myalgia have been reported for other second-generation BTK inhibitors [32][33][34]. In earlier studies, rash, diarrhea, headache, nausea, fatigue, and myalgia were reported in up to 33%, 58%, 69%, 27%, 21%, and 38% of patients in clinical trials of acalabrutinib [35,36].…”

Section: Discussionmentioning

confidence: 86%

Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies

et al. 2022

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Tirabrutinib is a Bruton’s tyrosine kinase inhibitor for treating B-cell malignancies. We report the final results of a Phase I study of tirabrutinib in 17 Japanese patients with B-cell malignancies. Patients were administered tirabrutinib at a dose of 160 mg, 320 mg, or 480 mg once daily, or 300 mg twice daily (N = 3, 3, 4, and 7, respectively). Three patients continued tirabrutinib until study completion (November 30, 2020). Adverse events (AEs) occurred in all 17 patients, with Grade 3–4 AEs in 8 (47.1%), serious AEs in 7 (41.2%), drug-related AEs in 16 (94.1%), and Grade 3–4 drug-related AEs in 6 (35.3%). Drug-related AEs reported in 3 or more patients were rash, vomiting, neutropenia, arthralgia, and malaise. One additional serious AE (benign neoplasm of the lung, unrelated to tirabrutinib) occurred after the previous data cutoff (January 4, 2018). Tirabrutinib administration and response assessment were continued for over 4 years in 4 patients. The overall response rate was 76.5% (13/17 patients). The median (range) time to response and duration of response were 0.9 (0.9–5.9) months and 2.59 (0.08–5.45) years, respectively. These findings demonstrate the long-term safety and efficacy of tirabrutinib in Japanese patients with B-cell malignancies.Clinical trial registration: JapicCTI-142682 (http://www.clinicaltrials.jp/).

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Section: Discussionmentioning

confidence: 86%

Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies

et al. 2022

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“…However, we did identify six clinical trials that reported the occurrence of TLS while on acalabrutinib for management of CLL/SLL (Table 3). [58][59][60][61][62][63] Four of the six trials involved acalabrutinib monotherapy whereas two studies involved multitherapy with obinutuzumab or venetoclax. The mean age of patients was 65.1 years and 68% were male.…”

Section: Acalabrutinibmentioning

confidence: 99%

“…The dose of acalabrutinib ranged from 100 to 200 mg daily. Four nonfatal TLS cases were reported with two during monotherapy 58,62 and two on multiagent therapy. 59,63 None of these studies used TLS prophylaxis.…”

Section: Acalabrutinibmentioning

confidence: 99%

Tyrosine kinase inhibitors and tumor lysis syndrome in hematologic malignancies: A systemic review

Salter

Burns

Fuller

et al. 2022

European J of Haematology

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Background Effective treatments for hematologic malignancies include therapies that target tyrosine kinase (TK) signaling pathways. Tumor lysis syndrome (TLS) is an oncologic emergency that can occur due to rapid turnover following the initiation of treatments for hematologic malignancy. The incidence of TLS is under‐reported and it is unclear as to whether TK inhibitors (TKIs) are associated with TLS. Objective To conduct a systematic review to determine the incidence of TLS with TKIs. Methods A search was performed using EMBASE, MEDLINE, and Web of Science electronic databases, as well as a manual search of the American Society of Hematology and American Society of Clinical Oncology abstract databases. Keywords included: “tumor lysis syndrome,” “tyrosine kinase inhibitors,” “lymphoma,” and “leukemia.” Results We identified a total of 57 publications that commented on the incidence of TLS with TKIs for hematologic malignancy. Thirty‐nine of those publications reported TLS as an adverse event. TLS was described as an adverse event among essentially all the subclasses of TKIs that are used to manage hematologic malignancies. Conclusion The overall number of articles commenting on TLS as an adverse event is sparse and there needs to be more transparency regarding the incidence of TLS when employing newer targeted therapies. Physicians should consider the risk of TLS on an individual basis and the added risk of TLS when using TKIs to treat hematologic malignancy.

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Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial

Yang,

Huang,

Zhou

et al. 2024

Ann Hematol

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Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor approved in the United States and Europe for chronic lymphocytic leukemia (CLL) based on phase 3 trials with limited representation of Asian populations. This phase 1/2 trial evaluates acalabrutinib in Chinese adults with relapsed/refractory (R/R) CLL receiving acalabrutinib 100 mg twice daily in 28-day cycles until disease progression or treatment discontinuation due to adverse events (AEs) presenting substantial clinical risk. The primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). A total of 60 patients from 20 sites in China received acalabrutinib (median age 62 years; median 1 prior therapy line; 21.7% with del(17p) and/or TP53 mutation; 51.7% with unmutated IGHV). Median total treatment duration was 19.4 months (range 0.6–28.2) with 53 patients (88.3%) receiving acalabrutinib at data cutoff; median study follow-up was 20.2 months. BICR-assessed ORR was 85.0% (95% CI, 73.4–92.9). Median duration of response, progression-free survival (PFS), and overall survival (OS) were not reached. Estimated 12-month and 18-month PFS rates were 91.5% (95% CI, 80.9–96.4) and 78.8% (95% CI, 60.9–89.2); OS rates were both 96.7% (95% CI, 87.3–99.2). AEs of grade ≥ 3 occurred in 25 patients (41.7%), most commonly decreased neutrophil count (13.3%, n = 8), pneumonia (6.7%, n = 4), and upper respiratory tract infection (6.7%, n = 4). AEs led to treatment discontinuation in 2 patients (paraneoplastic pemphigus; rectal neoplasm). This study demonstrated high ORR in acalabrutinib-treated Chinese patients with R/R CLL with no unexpected safety concerns. This trial is registered on ClinicalTrials.gov (NCT03932331).

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Safety and antitumor activity of acalabrutinib for relapsed/refractory B‐cell malignancies: A Japanese phase I study

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 8 publications

References 24 publications

Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies

Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies

Tyrosine kinase inhibitors and tumor lysis syndrome in hematologic malignancies: A systemic review

Acalabrutinib in Chinese patients with relapsed/refractory chronic lymphocytic leukemia: Primary analysis from an open-label, multicenter phase 1/2 trial

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