My name is Juan Bergua, I am from the Hospital San Pedro de Alcántara of Cáceres and on behalf of the PETHEMA Study Group I presented yesterday the updated results of the VEN-A-QUI clinical trial. This is a phase I/II of the combination of a triplet of quirzatinib plus venetoclax, comparing two arms: low dose cytarabine and azacitidine. This is a clinical trial for older patients than 70 years or more than 65 years who are unfit patients. So it’s for the more difficult population in order to be treated.
The trial consisted of two phases. In the phase I we worked to see the quirzatinib dose for the phase II, and in the phase II we made two groups, one based on low dose cytarabine and the other for azacitidine and compared the complete remission of both arms and the overall survival between both arms. There are other secondary objectives in this study.
In the first phase we found that the dose of quirzatinib with low dose cytarabine was 40mg and the dose of quirzatinib in the dose with azacitidine plus venetoclax was 60mg. In the phase II we compared two groups of 31 and 30 patients and we obtained a composite complete remission of 56% of the patients in the azacitidine arm and 50% in the arm with low dose cytarabine. Both arms were comparable in terms of ECOG, previous myelodysplastic syndrome that was in around 50% of both arms, and previous use of hypomethylating agents.
It was worth noting that there were two things significant in the study. The first one: we achieved 36% of patients with minimal residual disease negative in the arm with azacitidine. And, secondly, we have a high toxicity in terms of early death in the arm with azacitidine. We obtained the same rates of composite complete remission comparing azacitidine and low dose cytarabine and the overall survival was similar in both arms.
In a post-hoc analysis we see that patients with FLT3-ITD mutations, it was mandatory to include 12 patients, achieved a median overall survival that was not reached, better than the patients with wildtype FLT3 mutations. It was a investigation group. The second is that the patients with no previous myelodysplastic syndrome or acute myeloid leukaemia of de novo in older patients have a median overall survival that was not reached in comparison with patients with previous interference of myelodysplastic or myeloproliferative disease.
In terms of security, this is a very toxic way of giving chemotherapy for older patients, with both an increased number of neutropenia, febrile neutropenia, sepsis and pneumonia. So we think that this triplet can be used in older patients but reducing the dose of venetoclax and quirzatinib.
We performed two administrative treatment, the first one after phase I was to reduce the number of days of venetoclax in the first cycle of induction to 14 days if we, in the 14 days, performed a bone marrow aspiration and no blasts were present in the assessment of bone marrow. The second that patients who had complete remission we give to the patients only seven days of venetoclax in the following cycles. This is the clinical trial in older patients with a triplet.
It's important for one principal reason – we have to treat, to add a new drug to the combination of low dose cytarabine plus venetoclax or azacitidine plus venetoclax. The terms of toxicity of the associated drugs can be very important and perhaps the regulatory agencies must be looking for giving 20 days of venetoclax or the complete dose of low dose cytarabine or the azacitidine dose. In the case of triplets we have to look for a reduced dose of venetoclax and the associated dose of the combination because, if not, the problems about toxicity and neutropenia can be very important.