What Patients With Mantle Cell Lymphoma Should Know About the FDA's Approval of Brukinsa

Patients with mantle cell lymphoma (MCL) whose disease has relapsed or become resistant to other medications now have a new treatment option after the Food and Drug Administration (FDA) approved Brukinsa (zanubrutinib) for use in adult patients who have received at least one prior therapy for their cancer.

MCL is a type of non-Hodgkin lymphoma (NHL) that represents about 3% to 10% of all NHL cases in the United States, affecting approximately 15,000 patients.

“The issue with MCL is that it is an aggressive lymphoma, the five-year median overall survival is about five years, and it is regarded, as for most patients, incurable,” Dr. Lee Greenberger, chief scientific officer of The Leukemia & Lymphoma Society (LLS), said in an interview with CURE®. “Therefore, most patients given initial therapy with MCL are expected to relapse and need additional therapy. Hence, new therapies are critically needed.”

How Brukinsa Works

The FDA’s approval of Brukinsa is based on the results of two clinical trials. The first included 86 patients with MCL and examined how many patients had complete or partial shrinkage of their tumors after they received the therapy. The findings showed that 84% of patients had their tumors shrink and the time between the initial response to therapy and disease progression or relapse, also known as median duration of response, was 19.5 months. The second trial, which included 32 patients, also showed tumor shrinkage in 84% of patients and median duration of response was 18.5 months.

Brukinsa is an oral drug known as a Bruton’s tyrosine kinase (BTK) inhibitor. BTK inhibitors, such as Imbruvica (ibrutinib) and Calquence (acalabrutinib), block the BTK protein which may prevent malignant B cells from growing, and these types of medications have already proven to be effective in treating patients with MCL.

“The efficacy of these three agents is roughly similar, although the overall response rate and complete response rate is numerically higher with Brukinsa ... it is not clear that these differences are statistically distinct,” Greenberger said. “(This approval) gives patients another option that might be useful if intolerance to ibrutinib or acalabrutinib occurs. It is possible that Brukinsa will have a superior safety profile compared to ibrutinib.”

Side effects experienced while taking Brukinsa included decreased white blood cells that fight against infection, decreased platelet count, upper respiratory tract infection, decreased hemoglobin (oxygen-carrying protein in red blood cells), rash, bruising, diarrhea and cough.

While taking the medication, patients should use sun protection because there is risk of other malignancies including skin cancers, according to the FDA.

“On the safety side, the frequency of serious atrial fibrillation (irregular heartbeat) is less common with Brukinsa (2%) versus ibrutinib (approximately 6%) versus acalabrutinib (1%),” Greenberger said. “(However), these comparisons need to be made with caution because no side-by-side comparison are available.”

The Future of Mantle Cell Lymphoma

Patients with relapsed MCL tend to develop resistance to Imbruvica — roughly 30% of patients in initial therapy and 20% to 50% of patients after responding to therapy. “It is not clear why resistance to (Imbruvica) is so common (in MCL) compared to other diseases treated with (Imbruvica), such as chronic lymphocytic leukemia,” Greenberger said.

Therefore, it is important to develop new therapies for patients to try once their disease becomes resistant, he explained. “… resistance mechanism could also be distinct and perhaps less frequent with Brukinsa, especially if a patient can tolerate the medicine better than other agents and do not reduce the dose of Brukinsa while on therapy.”

Researchers working on current clinical trials are investigating combination therapies, including those that combine Imbruvica, Calquence and Brukinsa with chemotherapy agents, in several blood cancers. The LLS is funding some work on this in the MCL space and is conducting additional research with chimeric antigen receptor T cell therapy, a type of immunotherapy, in these patients. “The goal is to further decrease cancer burden and increase the time patients are disease-free,” Greenberger said.

Read CURE’s original coverage of the FDA’s approval of Brukinsa for patients with mantle cell lymphoma.