For a number of years we and others have used blinatumomab for our patients with Ph ALL who have not achieved MRD negativity with approaches such as TKI plus steroid alone. In order to study this in a more structured manner, and given the fact that we had seen good efficacy in series that we and others have published to date, we decided to initiate a phase II study. This is an investigator initiated study, it has just started up at MSK, there was a little bit of a delay due to the COVID pandemic, and we are hoping to open at another site shortly.
Basically, this is a phase II study investigating TKI therapy followed by blinatumomab with some similarities to the D-ALBA study but some important differences. First of all, this study will allow investigators and patients to change TKI therapy as indicated, based on intolerance to dasatinib or other factors at the discretion of the investigator. It will also introduce blinatumomab as early as six weeks into treatment. Now, as we saw in the D-ALBA study, and as we ourselves have seen, resistance to TKI plus steroid can emerge in a handful of patients as soon as six weeks into treatment. In fact, in the D-ALBA study in the range of around nine weeks into treatment is when they started to see some of these resistant clones emerge. In order to try to suppress that we decided to introduce the CD19 targeted therapy as early as six weeks in in patients who had achieved a morphologic complete response.
The other difference of note is that we’ve built in a blinatumomab maintenance programme. Ph ALL affects older adults predominantly and for many of those patients transplant may not be a great option or they may decline transplant. As such, we decided to investigate a programme of blinatumomab maintenance for patients who achieve a complete molecular response within three cycles of consolidation but are not proceeding immediately to transplant. Those patients can receive one month on, one month off, of blinatumomab for up to four additional cycles. Of course, we’ll be interested to see how that works as well.
This is just a small study, this is just a 17 patient study that has a Simon’s two-stage minimax design where we’ll enrol ten patients and if we see three or more complete molecular responses we’ll enrol up to 17. We are hoping that that will actually provide some prospective data from within the United States, as opposed to just within Europe, and will also demonstrate some preliminary data regarding the safety and feasibility of blinatumomab consolidation in patients who are not proceeding directly to an allograft.
It’s going to be a while before we see the results of the ECOG 9181 study which I commented, which will be the forthcoming TKI plus steroid versus TKI plus chemo comparison. We’re hoping that our study will provide some information to the community while we’re awaiting the larger randomised trial and, in some ways, will allow us to explore some factors that were not investigated prospectively in the D-ALBA study.
Are there any recent updates on this study?
This is a trials in progress so we are not presenting the results at this meeting. The goal of the poster was to basically show the investigators in the New York area that if they have patients with newly diagnosed Ph ALL and they’re looking for a chemo-free approach that we have this study open and available and that we’re actively enrolling. But we are not sharing results at this meeting, this is essentially just a trials in progress to let folks know of the concept and the ongoing study.
Is there anything you would like to add?
That’s a great question. The results from this study will certainly help to solidify that across multiple centres and multiple approaches whether TKI plus blinatumomab consolidation is associated with the rates of deep and durable response that have been suggested by the small series to date and may firmly establish this as an alternative approach to TKI plus chemo consolidation which has become more standard of care. Then, of course, as the data mature from this study and from others we’ll have a better sense of what the natural history is for patients who do well with an approach like this but who do not proceed to transplant. That will be more important information as well as we help our patients navigate decisions such as whether or not to proceed to transplant in first remission. We hope that that will, again, be a significant help to physicians in this space who are having these conversations with their patients.