One of the studies that I’m presenting at EHA is about the use of blinatumomab in the frontline setting in a chemo-replacement strategy. What we were doing is looking at risk factors in that particular scenario.
What was the study design?
The study design is a real-world cohort, so patients received blinatumomab at the clinician’s discretion, either because they had high-risk disease or they had existing comorbidity or they had toxicity to chemotherapy that prevented them from carrying on that standard chemotherapy pathway. So patients received blinatumomab at different timepoints and for different reasons. So that heterogeneity is a key aspect of the cohort, which is both a strength in the sense that it’s real world but it’s also a limitation in the sense that it’s quite heterogeneous in the way that the patients were treated. So it’s not like a clinical trial.
What were the key results?
The key result of this study is that in this particular scenario of treating patients with blinatumomab frontline in a chemo-replacement strategy, the risk factors for blinatumomab response and relapse after blinatumomab are quite different from the traditional risk factors that are usually used within paediatric ALL. So MRD, or minimal residual disease, after blinatumomab is very important, particularly after the first cycle. But the MRD level prior to blinatumomab is not predictive of relapse.
In terms of genetics, the traditional high-risk genetic risk factors don’t seem to play a major role in the risk of relapse after blinatumomab. Instead, DUX4 rearrangement seems to have a higher than expected relapse rate and also a slower response to blinatumomab and also patients with the Ikaros+ profile also have a high risk of relapse after frontline blinatumomab.
What could be the clinical significance of these results?
The clinical significance of these results are that if we are going to introduce blinatumomab into frontline therapy we need to be very cautious about exactly how we do it for different types of patient. So our results need to be validated in a larger cohort and with longer follow-up. But they certainly indicate that not all patients will respond equally to blinatumomab, especially when given with reduced chemotherapy. It might be that different patients require different strategies depending on their genetic background and their initial response to blinatumomab.
What’s next for the study?
What we’d really like to do is validate our findings in a larger cohort. We are struggling at the moment to find such a cohort because, of course, not that many patients are being treated with blinatumomab in a frontline setting and also have comprehensive genomic workup. So that’s our first step is to try and do that. In the UK we are also altering the guidelines on use of blinatumomab in the frontline setting depending on the genetic background of the patient.
