MURANO trial: Venetoclax-rituximab shows sustained benefit in relapsed/refractory chronic lymphocytic leukaemia
Dr John Seymour - Peter MacCallum Cancer Centre, Melbourne, Australia
I presented here the four year analysis of the MURANO study. Previous analyses of earlier efficacy endpoints showing improved progression free survival and overall survival had previously been published. So the focus here was on what happens in the patients who cease therapy. The design of the study was a time-limited two-year treatment with venetoclax and rituximab and then in all patients ceasing therapy at that two year time-point.
We’ve now got a median of 22 months of follow-up in the 130 patients who got to that two year time-point. Overall 68% of those remain progression free, really reinforcing that the time-limited treatment approach provides good disease control and durable time off treatment for the majority of patients.
The main conclusions were that we were able to confirm the progression free survival benefit - at four years 57% compared to 5% remained progression free; strengthen the overall survival benefit – again at four years 85% compared to 57% with bendamustine rituximab treatment remain alive; and were able to now, for the first time, look at sensitivity to subsequent therapy after disease progression from venetoclax and rituximab. So there were two main groups that we looked at there, one was those who had been treated with a different class of drug, the BTK inhibitors such as ibrutinib. With ten evaluable patients at the moment all ten of those have obtained disease response.
The second group we looked at were those who were re-treated with venetoclax. So they’ve had initial venetoclax rituximab, achieved some degree of response and had treatment ceased, and in this group at a median of 17 months subsequently have had disease progression and retreatment. At the moment we only have eleven patients evaluable and it’s still fairly early in their retreatment but already six of those eleven have demonstrated disease response, showing that you have persistent sensitivity and can regain disease control with re-exposure.
The next step with this study is really to look in greater detail about the exact rate of disease response and how deep those responses are when you re-expose patients to venetoclax and rituximab - it could be that there is a subgroup, perhaps those with early progression, where we may not have maintained sensitivity; identifying which group are best retreated or which may be better treated with alternative agents and also in the very long term to look at the development of resistant mutations. Because we know that continuous therapy tends to select for these resistant clones and the ultimate aim of the concept of intermittent treatment is to delay or prevent the development of these resistant clones. So the hypothesis is that we will achieve that but it’s too early to know and we will need to look at serial samples in these patients to determine whether we are achieving that goal.
