ASH 2024 | Valemetostat monotherapy in patients with R/R LBCL: primary results of the VALYM trial

Well, I have the privilege today to present on behalf of my co-authors the results from the VALYM study. The VALYM study is a Phase II study regarding the use of valemetostat tosylate, an EZH1 and 2 dual inhibitor that is already approved in Japan for PTCL and ATLL, and the study was about B-cell non-Hodgkin lymphoma. And here we report the results of a sub-cohort of this trial regarding large B-cell lymphoma. 

So 41 patients were involved. They needed to have received at least two previous lines of treatment. The treatment was given orally, 200 mg per day, with continuous cycles of 28 days until progression. and the patient characteristics show that this is a very elderly patient population. The median age is 75 and the oldest patient is 91, showing that it’s quite well tolerated in fact. The patients were heavily pretreated, median line of pretreatment was four, and half of the patient’s population had received CAR T-cell, and one patient out of four had received a previous CD3/CD19 bispecific antibodies. 

So regarding the results, the overall response rate is 37%. So it’s above the 30% threshold that was in the statistical hypothesis. So the trial is positive. The complete response rate is quite low, it’s 12%, but behind this proportion, there is a high variability depending on the biological feature of the large B-cell lymphoma. What we’ve seen is that also the numbers are quite small, among the patients with EZH2 mutation, the complete response rate is 25%, and among the patients with EZB subtype, a patient with either EZH2 mutation or BCL2 translocation, the complete response rate is 50%. 

So the safety profile shows that it’s quite well tolerated. There are 25% of patients that have Grade 3 or 4 thrombocytopenia, but it’s a safety profile that is known for the drug based on PTCL studies. And there are some GI tract safety concerns, but very low grade, Grade one or two GI toxicity. 

So in conclusion, the trial showed encouraging overall response rate and complete response rate in specific biomolecular subtypes. Much more encouraging than what we’ve seen with tazemetostat so far, and the studies are ongoing in combination with this drug in large B-cell lymphoma.

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