A clinical trial for the drug zanubrutinib shrunk tumours in 80% of patients suffering from difficult-to-treat lymphoma cancer.
A team of researchers at the University of Michigan Health Rogel Cancer Center conducted a clinical trial for the drug zanubrutinib. The existing drug was used for treating follicular and marginal zone lymphoma. According to the study published in the journal Blood Advances, the researchers recruited 33 people with follicular lymphoma and 20 with marginal zone lymphoma. All patients had relapsed/refractory lymphoma.
Lymphoma is a type of cancer that begins in the lymphatic system. This is responsible for producing infection-fighting lymphocytes which are present in the lymph nodes, spleen, bone marrow, thymus gland, and other parts of the body. When cancer cells grow in these areas, people may experience painless and swollen lymph nodes, fever, fatigue, fever, and night sweats.
There are two main types of lymphoma – Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is the most commonly diagnosed cancer in children aged 15 to 19 years. In 2020, more than 80,000 people worldwide developed Hodgkin Lymphoma. On the other hand, non-Hodgkin lymphoma is more common in older adults, mostly 75 years or older.
Although lymphomas are treatable, certain subtypes are highly resistant to current treatments. The marginal zone and follicular lymphoma are two subtypes that are considered incurable due to their unresponsiveness to standard chemoimmunotherapy regimens. In both follicular and marginal zone lymphoma, B cells of the immune system become damaged and start to divide uncontrollably. Thus, forming a tumour.
Due to the limited treatment options for these cancers, researchers from the University of Michigan aimed to find better and safer treatments. Therefore, they turned their attention to zanubrutinib, an existing drug currently used for treating other types of lymphomas.
How Does Zanubrutinib Work?
Sold under the brand name Brukinsa, zanubrutinib is a second-generation Bruton’s tyrosine kinase (BTK) inhibitor. The BTK protein is a signalling enzyme that helps B cells communicate and develop. Inhibiting the signalling enzyme then prevents the uncontrollable division of the tumour cells in patients. The oral drug is currently approved for the treatment of mantle cell lymphoma (MCL), Waldenström’s macroglobulinemia (WM), and marginal zone lymphoma (MZL).
As part of the trial, each patient received a phase 2 dose of zanubrutinib. According to the results, 80% of the 20 patients with marginal zone lymphoma saw shrinkage in their tumours. However, those with follicular lymphoma lower response had a significantly lower response. Only 36.4% of them showed a response to treatment.
Furthermore, about one-fifth of marginal zone lymphoma patients and 18% of follicular zone lymphoma patients showed no sign of cancer at the follow-up appointment. Thus, revealing that they had gone into remission. Imaging tests showed no tumour in these patients.
Regardless, the drug had a favourable safety and tolerability profile. The researchers did not report any serious adverse effects among the study participants. Rashes, diarrhoea, fever, lower white blood cell counts, and bruising were the most frequent side effects among the group.
20% of Lymphoma Patients Go into Remission
The results of the study reveal the effectiveness of the drug against hard-to-treat lymphomas, especially marginal zone lymphoma. The US Food and Drug Administration (FDA) has now approved zanubrutinib on a contingent basis for adults with refractory or relapses marginal zone lymphoma. Study authors now call for a larger trial to assess the drug’s efficacy for these and other hard-to-treat cancers.
Despite the study’s limitation, the researchers are hopeful that zanubrutinib can serve as an important option, especially in addition to other therapies.
Recently, another drug trial revealed ground-breaking results for treatment-resistant cancer. The team at Memorial Sloan Kettering Cancer Center trialed an experimental therapy in patients with early-stage rectal cancer. All patients had mismatch repair-deficient rectal cancer which respond poorly to chemotherapy drugs. The researchers administered dostarlimab, a PD-1 inhibitor, to the patients. As a result, all 12 trial participants saw a complete disappearance of their tumours. At their 6-month follow-up, researchers conducted MRI scans, digital rectal examination, and visual endoscopic inspection. All of which showed a clinical complete response. PET scans and biopsies further confirmed their remission status.
Moreover, none of the patients required chemotherapy, radiation, or surgical resection after the treatment. Nor did any patients have a recurrence or tumour progression. The trial is currently ongoing.
Tycel Phillips, Henry Chan, Constantine S. Tam, Alessandra Tedeschi, Patrick Johnston, Sung Yong Oh, Stephen Opat, Hyeon-Seok Eom, Heather Allewelt, Jennifer C. Stern, Ziwen Tan, William Novotny, Jane Huang, Judith Trotman; Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv 2022; 6 (11): 3472–3479. doi: https://doi.org/10.1182/bloodadvances.2021006083