In November 2019, the FDA approved the third Bruton tyrosine kinase (BTK) inhibitor, Brukinsa (zanubrutinib), for the treatment of mantle-cell lymphoma. BTK inhibitors represent a drug class that was initially approved for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
It is therefore not surprising that Brukinsa is also being investigated for CLL or SLL, and the results from 2 recent clinical trials were presented at the American Society of Hematology in December 2019. Treatment with Brukinsa led to a high overall response rate and durable responses, including patients with high-risk genetic abnormalities.
In the first study, 92.7% of patients with CLL or SLL and deletion 17p (or del 17p) who had not received previous treatment had a response to Brukinsa treatment. In the second study, 100% of patients who had not received treatment before had a response to Brukinsa, as well as 95% of patients with relapsed (coming back) or refractory (not responding to treatment) CLL.
“Zanubrutinib monotherapy was found to be well-tolerated and active in patients with CLL or SLL, irrespective of del 17p status, with very high response rates,” said lead investigator Constantine S. Tam, MBBS, MD, FRACP, FRCPA, of the Peter MacCallum Cancer Centre in Melbourne, Australia.
Imbruvica (ibrutinib) was the first BTK inhibitor to be approved by the FDA for CLL or SLL, followed by Calquence (acalabrutinib). Brukinsa became the third BTK inhibitor to be approved by the FDA. It has different pharmacologic qualities from the other 2 BTK inhibitors, but all 3 have led to impressive responses.
The first study included high-risk patients who were unfit for chemotherapy. Many patients had biologic abnormalities, such as del 17p, IGHV mutation, del 13q, del 11q, Trisomy 2, and bulky disease, all of which complicate the treatment and lead to poor prognosis.
After an average of 10 months of treatment with Brukinsa, the overall response rate was 92.7%, including 2 patients with complete responses, 86 with partial responses, and 13 patients with partial responses and lymphocytosis. Most (95%) patients had a response that lasted 6 months or longer.
The time from beginning of treatment to the response to treatment was quick, according to Dr. Tam. Furthermore, “All subgroups had high response rates, including poor prognostic groups,” he said.
After 10 months of treatment, 1 patient died despite treatment, and 4 patients still had progressive disease despite treatment.
The second study continued for a longer follow-up period, and patients continue to have high and durable responses to Brukinsa therapy.
“Zanubrutinib monotherapy is well-tolerated and is active in CLL or SLL, irrespective of del 17p,” Dr. Tam emphasized. “At the time of assessment, all patients continue to respond. Responses continue to mature over time, with a gradual reduction in lymphocytosis and a gradual rise in complete response rate,” Dr. Tam added.
Almost all (95%) of the patients who had not received previous therapy had no disease progression after 12 months of treatment with Brukinsa, which increased to 97% of patients after 24 months of treatment.
For patients with relapsed or refractory disease, 97% of the patients had no disease progression by 12 months, which was reduced to 91% by 24 months of treatment.
The most common side effects seen with Brukinsa were contusion, respiratory infection, diarrhea, cough, headache, and fatigue.
After an average of 2.5 years of treatment with Brukinsa, all patients had some side effects, and almost 47.2% had serious side effects.