Clinical Report: Zanubrutinib Alone in CD79B-Mutated R/R DLBCL
Overview
In this open-label, single-arm phase 2 trial, 65 Chinese patients with CD79B-mutated relapsed or refractory diffuse large B-cell lymphoma (DLBCL) received zanubrutinib monotherapy. At a median follow-up of 13.9 months, the investigator-determined overall response rate was 46.2% (95% CI, 33.7–59.0), including complete responses in 29.2%; the response rate exceeded the prespecified 30% historical control.
Background
DLBCL is clinically and molecularly heterogeneous, and approximately one in three patients experiences relapsed or refractory disease after frontline immunochemotherapy. CD79B mutations occur in an estimated 5%–25% of DLBCL cases and are associated with chronic active B-cell receptor signaling and constitutive NF-κB pathway activation. These mutations are enriched in the activated B-cell–like/non-germinal center B-cell subgroup. Because BTK mediates B-cell receptor signaling, its inhibition provides a biological rationale for study in CD79B-mutated DLBCL, although prospective evidence for BTK-inhibitor monotherapy in this population has been limited.
Data Highlights
Measure
Result
Patients enrolled and treated
65
Median age (range)
66 years (42–92)
Median prior treatment lines (range)
1 (1–6)
Non-GCB disease
86.2%
Median observation (range)
13.9 months (0.5–36.4)
Overall response rate (95% CI)
46.2% (33.7–59.0)
Complete response rate
29.2%
Comparison with prespecified 30% historical control
P = 0.0044; one-sided binomial exact test
Key Findings
The trial was an open-label, single-arm, multicenter phase 2 study in Chinese adults with histologically confirmed R/R DLBCL and a CD79B mutation identified by a validated PCR assay.
Zanubrutinib was administered orally at 160 mg twice daily in uninterrupted 28-day cycles until disease progression, unacceptable toxicity, or study discontinuation.
Of 65 treated patients, 63.1% had relapsed disease and 36.9% had disease refractory to their most recent treatment; 81.5% had stage III–IV disease.
After a median observation of 13.9 months, the investigator-determined ORR was 46.2% (95% CI, 33.7–59.0), with a CR rate of 29.2%.
The ORR exceeded the prespecified 30% historical control (P = 0.0044) using a one-sided binomial exact test with a Type I error rate of 0.025.
The supplied article excerpt does not report the remaining time-to-event outcomes, detailed safety results, or exploratory biomarker findings; these results therefore cannot be summarized here.
Clinical Implications
The reported response results provide prospective evidence of antitumor activity for zanubrutinib monotherapy in this molecularly selected cohort. The study was single-arm and compared its response rate with a historical control; the supplied excerpt does not provide comparative efficacy, detailed safety outcomes, or enough information to establish a treatment recommendation.
Conclusion
In this phase 2 study of CD79B-mutated R/R DLBCL, zanubrutinib monotherapy produced an ORR of 46.2% and a CR rate of 29.2% at a median observation of 13.9 months. Further interpretation is limited by the single-arm design and the outcome details absent from the supplied excerpt.
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