Novel research published in Blood has found that combining targeted B-cell lymphoma drug tazemetostat with DOT1L inhibitor pinometostat can benefit cancer patients significantly.
The paper also touts the benefits of combining tazemetostat with pinometostat in patients with the most common type of B-cell lymphoma, potentially impacting thousands of patients.
Tazemetostat is commonly prescribed to patients with follicular lymphoma, though responses vary dramatically, with some seeing their cancer return.
Diffuse large B-cell lymphoma is the most common type of B-cell lymphoma, though tazemetostat is not approved for patients with this indication.
To assess how healthcare can get the most of out tazemetostat in terms of patient responses and cancer management, researchers at the Institute of Cancer Research (ICL) London, worked in the SPECIFICANCER team, which was funded by Cancer Research UK and the Mark Foundation for Cancer Research.
Notably, the SPECIFICANCER team have previously shown that drugs such as tazemetostat can be more effective for other hard-to-treat cancers such as triple-negative breast cancer and colorectal cancer, when used in combination with other drugs.
Tazemetostat & pinometostat: a key combo?
To assess what should be combined with tazemetostat to get the best results, ICR researchers knocked out genes in B-cell lymphoma cells in the presence and absence of the therapeutic.
Through this, they found that DOT1L is needed to interact with the drug to block cell growth, meaning that combining the drug with a DOT1L inhibitor can shrink follicular lymphoma tumours in the lab — even if they've developed resistance to tazemetostat.
This combination also proved effective in DLBCL cells, stopping tumours from growing in this group of patients. There were also no major side effects from this treatment in mice.
The cells treated with the combination of drugs had more genes switched on linked to growth inhibition and cell death, as well as immune functions than those treated with one drug alone.
Pinometostat, the DOT1L inhibitor used in this research, is currently in clinical trials.
“Tazemetostat is a promising drug but unfortunately, many patients’ cancers either do not respond or they start growing again quickly. It’s exciting to see that combining it with a DOT1L inhibitor could allow thousands more people to benefit from the treatment,” noted Dr Van Nguyen, Postdoctoral Training Fellow at The Institute of Cancer Research, London, and study co-author.
“We need to have more treatment options available to patients that will keep their cancer at bay for longer – and overcome cancer’s ability to adapt, evolve, and become drug resistant. Combining drugs which have different mechanisms of action is an important tool in our arsenal to do this," added Professor Kristian Helin, Chief Executive at The Institute of Cancer Research, London, and study lead.
“For some types of blood cancer, we have shown that combining the targeted drug tazemetostat with an inhibitor of the DOT1L enzyme could shrink tumours that have stopped responding to tazemetostat treatment alone. We have also shown that the drug combination could work for patients with diffuse large B-cell lymphoma – which has not previously responded to tazemetostat treatment.
“Expanding the use of a drug which is already clinically approved will hopefully mean that more patients can benefit sooner, and I look forward to seeing clinical trials designed to test this combination in patients," he concluded.