A single-arm, multicenter phase II trial held in China analyzed the Bruton’s tyrosine kinase inhibitor zanubrutinib for treatment of patients with relapsed/refractory mantle cell lymphoma. Previously, the investigational BTK inhibitor gained a breakthrough designation from the FDA based on early results from the phase II trial that showed zanubrutinib to be highly active.<br />
Yuqin Song, MD, PhD,
A single-arm, multicenter phase II trial held in China analyzed the Bruton’s tyrosine kinase (BTK) inhibitor zanubrutinib (BGB-3111) for treatment of patients with relapsed/refractory (R/R) mantle cell lymphoma. Previously, the investigational BTK inhibitor gained abreakthrough designation from the FDAbased on early results from the phase II trial that showed zanubrutinib to be highly active.
Patients with R/R mantle cell lymphoma were enrolled from 13 different centers throughout China and were given zanubrutinib (160 mg twice daily). The 86 patients enrolled were treated until they had disease progression or severe toxicity. The primary endpoint was an independent review committee assessment of overall survival, and secondary endpoints included safety, progression-free survival (PFS), time to response, duration of response (DOR), and investigator-assessed overall response rate (ORR).
The most recent data were presented at the 15th International Conference on Malignant Lymphoma with a median of 13.9-months follow-up. The median PFS was 16.7 months and the median DOR was 14.0 months (range, 2.32-14.0). The ORR was 84.7% (95% CI, 75.3%-91.6%), consisting of complete responses in 76.5% of patients and partial responses in 8.2%. One additional patient had stable disease.
Treatment-emergent adverse events were observed in 96.5% of patients, with grade ≥3 events noted in 39.5%. Treatment was discontinued in 29 (33.7%) patients due to disease progression and adverse events, namely decreased white blood cell count, upper respiratory infection, decreased platelet county, diarrhea, and hypokalemia. From these data, the researchers were able to substantiate previous claims of high clinical activity with zanubrutinib for the treatment of patients with R/R mantle cell lymphoma.
In an interview withTargeted Oncology, Yuqin Song, MD, PhD, chief physician and deputy director of the Lymphoma Department at Peking University Cancer Hospital in Beijing, China, explains the need to analyze the response from zanubrutinib in patients with mantle cell lymphoma in China.
TARGETED ONCOLOGY: Can you discuss the rationale for the phase II trial of zanubrutinib in patients with relapsed/refractory mantle cell lymphoma?
Song: As we know zanubrutinib has achieved high efficacy in [patients with] relapsed and refractory mantle cell lymphoma. This new agent has moved forward as a frontline treatment in select patients with mantle cell lymphoma.
I'm not a research scientist, but I know that zanubrutinib [is a good] agent for BTK [inhibition]. It was designed to maximize the BTK target and minimize the off-target effects of TEC and EGFR family kinases. In preclinical studies, it showed very high efficacy in relapsed or refractory mantle cell lymphoma. It is [also] a highly potent, selective, and irreversible BTK inhibitor.
In China, the BeiGene company sponsored a pivotal phase II study of patients with relapsed and refractory mantle cell lymphoma. At the last American Society of Hematology Annual Meeting, I presented the data assessed by the independent review committee. Their cut-off date was March of last year. Now, in this meeting, I gave an oral presentation of the updated data assessed by the investigators.
The data surprised us. The median follow-up time was over 18 months and the overall response rate, by investigator assessment, was 84%, the complete response rate was 78%, and the progression-free survival rate at 15 months was about 72%. The duration of response at 15 months was about 67%. I think these are good data and the safety profile is also quite good.
TARGETED ONCOLOGY:How do you see this treatment fitting into the treatment landscape among existing options for mantle cell lymphoma?
Song: That’s a difficult question. Before the BTK inhibitors became commercial products, we preferred bortezomib (Velcade) in relapsed or refractory [patients with] mantle cell lymphoma in China. Now, BTK inhibitors are a preferred choice for [patients with] relapsed or refractory mantle cell lymphoma in most countries, and also in China. In our center, when patients relapsed from BTK inhibition, we gave intensified bortezomib-based chemotherapy.
TARGETED ONCOLOGY: Are there any other agents or combinations under investigation for mantle cell lymphoma?
Song: In China, we have bendamustine, [which] just got approved by the CDA. [We] also have lenalidomide (Revlimid), [which is a good choice for frail patients]. We also have several different CAR T-cell therapy products in our center.
Song Y, Zhou K, Zou D et al. Zanubrutinib in Patients with Relapsed/Refractory Mantle Cell Lymphoma. Presented at: 15th International Conference on Malignant Lymphoma Palazzo dei Congressi; Lugano, Switzerland; June 18-22, 2019.