EHA 2023 | Mini-hyper-CVD + InO followed by blina consolidation for R/R ALL

Yeah, so, the outcomes of patients with relapsed/refractory B-cell ALL have historically been very poor. But fortunately, now we have new treatments such as blinatumomab, inotuzumab ozogamicin, and several CD19 CAR-T cell therapies. And so what we’re doing in this study is we’re evaluating patients with relapsed/refractory B-cell ALL, treating them with low intensity chemotherapy, so a mini hyper-CVD regimen, in combination with inotuzumab and blinatumomab to see if we can increase response rates, deepen responses, and maybe even eventually overcome the need for transplant in some of these patients. So this study has gone over, has had several different iterations and amendments. Initially we started with chemotherapy and inotuzumab, then we introduced blinatumomab, and then now more recently we’re using what we call a dose-dense regimen, which is a combination of chemotherapy, inotuzumab and blinatumomab, all given starting as early as cycle one.

So we treated 125 patients, around 60 with the first, before we introduced blinatumomab and then about another 60 after adding blinatumomab. And we see very high rates of response. The response rate, particularly in salvage one, the response rate is 98%. We see the vast majority of patients becoming MRD negative. We have seen an improvement in outcomes after we’ve added blinatumomab suggesting that there is an additive benefit of introducing blinatumomab early for these patients. And we’ve seen some very encouraging data with the early iteration of the study, with the new amendment, with the dose-dense regimen – with the inotuzumab and blinatumomab being given beginning in cycle one, with very high rates of MRD negativity at the end of the first cycle.

Interestingly, we’ve also done an analysis looking at the impact of transplant. We don’t see a significant impact of transplant, which is very unique in the relapsed/refractory setting because historically, this has been the standard of care. And so further studies are needed to identify those patients who may or may not benefit from transplant. We’ve been very encouraged by the data so far, in first Salvage, we actually have a three-year survival of around 50%, which is much higher than we’ve seen with any of these drugs as single agents. So we really believe that this is how we should be treating patients with B-cell ALL, both in the frontline setting or relapsed refractory setting. We need to use all of our most effective agents as early as possible in the treatment course and ideally in combination.