16 March 2018

People being treated for lymphoma could benefit from a new epigenetics therapy, a European conference has heard.

Data presented to delegates at the TAT (Targeted Anticancer Therapies) International Congress 2018 in Paris, France, has demonstrated that new compounds targeting epigenetic regulation have shown “remarkable” early activity.

The European Society for Medical Oncology’s phase-I oncology meeting featured early clinical studies with BET inhibitors and EZH2 inhibitors.

Dr Anastasios Stathis, head of the New Drugs Development Unit of the Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland, one of the first oncologists to research this field, said BET inhibitors have shown some activity in leukaemia and lymphoma, as well as NUT carcinoma.

His previous phase I research on the first-in-class BET inhibitor birabresib (OTX015/MK-8628) showed some activity in diffuse large B-cell lymphoma.

In clinical trials, preliminary results have confirmed that BET inhibitors may be effective in patients with diffuse large B-cell lymphoma and NUT carcinoma, although some side effects have been observed that may limit treatment compliance, such as thrombocytopaenia, fatigue and gastrointestinal symptoms.

Dr Stathis said: “It’s not clear what the real clinical impact of BET inhibitors could be. Compounds approved for lymphoma in the last five years had single-agent phase-I response rates above 30%, but activity with BET inhibitors is less than 30%.

“The hope is to identify the patients that would benefit most and test BET inhibitors in combination with other compounds. In addition, there are new classes of BET inhibitors in preclinical studies and we need to wait to see if they have better activity.”

Clinical data on EZH2 inhibitors was also being presented at TAT 2018. A study in patients with B-cell lymphoma showed evidence of anti-tumour activity with an EZH2 inhibitor, which was well-tolerated and had manageable level of toxicity.

Study author Dr Adrian Senderowicz, of Constellation Pharmaceuticals, Cambridge, USA, said: “If approved by health authorities, EZH2 inhibition may become a new treatment paradigm in relapse or refractory EZH2 mutant follicular lymphoma patients.”

A previous study showed that another EZH2 inhibitor, tazemetostat, induced objective response rates of 92% in patients with EZH2 mutant follicular lymphoma and 26% in those with the wild-type.


Source: European Society for Medical Oncology


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