A groundbreaking study conducted by researchers at The Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC—James) has introduced a promising new treatment option for patients battling blood cancers. This novel targeted drug, known as nemtabrutinib, has shown remarkable efficacy in patients with chronic lymphocytic leukaemia (CLL) and Non-Hodgkin lymphoma (NHL) whose disease has become unresponsive to conventional treatments.
The results of the first clinical trial of nemtabrutinib in humans, published in the journal Cancer Discovery, reveal that this drug was effective in approximately 75% of the cancer patients tested and caused minimal severe side effects.Â
Lead investigator and haematologist, Dr. Jennifer Woyach, emphasizes the significance of this discovery. While several drugs are available for treating B-cell cancers like CLL and NHL, many patients eventually experience disease progression despite initially responding to these medications. Patients who have relapsed after initial treatments often face the challenge of limited treatment options, and nemtabrutinib offers hope in addressing this critical issue.Â
The mechanism of action of nemtabrutinib is pivotal to its success. When antigens, such as viruses or bacteria, enter the bloodstream, they trigger a series of signals in B-cells to produce antibodies. However, in some individuals, this process malfunctions, causing B-cells to divide uncontrollably, leading to cancer.
Drugs designed to combat B-cell cancers target a key enzyme called Bruton’s tyrosine kinase (BTK), which plays a crucial role in the signalling process. These drugs inhibit the action of the BTK enzyme, ultimately causing abnormal B-cells to die.Â
The researchers conducted their clinical trial with 47 patients who had undergone at least two previous therapies for their blood cancer. Over half of these patients had relapsed CLL, while the others had NHL. The trial involved administering different doses of nemtabrutinib to the patients and closely monitoring their responses and side effects.Â
The results were highly encouraging, with more than 75% of patients with relapsed CLL responding positively to the drug, particularly at an optimal dose of 65mg. This response also extended to patients with mutations in BTK. Importantly, most patients remained cancer-free for at least 16 months during the trial. While it is common for chemotherapeutic drugs to cause side effects, the majority of these were mild and manageable, underscoring the safety of nemtabrutinib.Â
The impact of blood cancers on public health in the United States is significant, with one person losing their life to these diseases every nine minutes, and a new diagnosis occurring every three minutes. The specific blood cancers studied in this trial primarily affect B lymphocytes, a type of white blood cell responsible for producing antibodies and fighting infections. CLL stands out as the most common leukemia among adults, accounting for a quarter of leukaemia cases, while NHL contributes to 4% of all cancer cases in the United States.Â
The research conducted at OSUCCC—James has uncovered a potential breakthrough in the treatment of blood cancers with the introduction of nemtabrutinib, a targeted drug that offers hope to patients who have exhausted standard treatment options.
Its unique mechanism of action and promising results in the clinical trial indicate that it could significantly improve the prognosis and quality of life for individuals battling these devastating diseases. Further research and larger-scale trials will play a pivotal role in confirming the drug’s efficacy and safety, offering renewed optimism for those affected by blood cancers in the United States and beyond.Â
Journal Reference Â
Jennifer A. Woyach et al, First in Human Study of the Reversible BTK Inhibitor Nemtabrutinib in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia and B-Cell Non-Hodgkin Lymphoma, Cancer Discovery (2023). DOI: 10.1158/2159-8290.CD-23-0670.Â
