Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma

Abstract

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1–24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Keywords:

• Tyrosine protein kinase inhibitors
• leukemia, lymphocytic, chronic, B-cell protein
• survival analysis

Acknowledgments

We thank the investigators and coordinators at each of the clinical sites; the patients who participated in this trial and their families; employees of AstraZeneca who contributed to this trial, including Roser Calvo, Paulo Miranda, Simon Rule, and Jack Roos for reviewing the manuscript. The study was funded by AstraZeneca. Medical writing assistance, funded by AstraZeneca, was provided by Maria Ali, PhD, of Peloton Advantage, LLC, an OPEN Health company, under the direction of the authors.

Contribution

JZ designed the study, was a study investigator, and collected and assembled data. YS, JL, KZ, XK, ZC, and HZ were study investigators, provided patients and study materials, and collected and assembled data. TY, ZX, YW, PL, and XL performed data analysis. All authors interpreted data, prepared the manuscript, and participated in the critical review and revision of this manuscript and provided approval of the manuscript for submission.

Disclosure statement

YS, JL, KZ, XE, ZC, HZ, JZ: No conflict of interest to declare.

TY, ZX, YW, PL, and XL: Employees of AstraZeneca.

Data sharing statement

Data underlying the findings described in this article may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Data for studies directly listed on Vivli can be requested through Vivli at www.vivli.org. Data for studies not listed on Vivli can be requested through Vivli at https://vivli.org/members/enquiries-about-studies-not-listed-on-the-vivli-platform/. AstraZeneca Vivli member page is also available outlining further details: https://vivli.org/ourmember/astrazeneca/.