Chemotherapy-free combination of ponatinib and blinatumomab results in high rates of CMR and NGS MRD negativity in Ph positive ALL

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Published: 16 Jun 2023
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Dr Nicholas Short - MD Anderson Cancer Center, Houston, USA

Dr Nicholas Short speaks to ecancer at EHA 2023 about a phase II study evaluating a chemotherapy-free combination of ponatinib and blinatumomab for patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia.

He reports that all patients responded and the combination saw very high rates of MRD negativity.

Dr Short explains that only 1 out of the 60 treated patients underwent a transplant meaning that it can also be a regimen that overcome the need for transplant.

So, this year we’re presenting updated data from our ongoing clinical trial of a chemotherapy-free regimen of ponatinib and blinatumomab in patients with newly diagnosed Philadelphia chromosome positive ALL. As background, the standard-of-care for these patients historically has been intensive chemotherapy with a tyrosine kinase inhibitor. We’ve shown very good results with hyper-CVAD chemotherapy with ponatinib, with very deep or high levels of MRD negativity and a long-term survival around 75%, with most patients not needing transplant in first remission. There’s also some data from the D-ALBA study from the group in Italy showing a chemotherapy-free combination of dasatinib and blinatumomab is also effective in this patient population; they reported a four-year survival of 78%. So we wanted to see if we can improve upon that using a more potent TKI, ponatinib, in combination with blinatumomab for another chemotherapy-free regimen.

For patients with newly diagnosed Philadelphia chromosome positive AL we gave five cycles of blinatumomab in combination with ponatinib, initially at 30mg daily, and then we decreased to 15mg daily once they achieved complete molecular response. We also gave 12 doses of intrathecal prophylaxis to prevent CNS relapse. We’ve seen very encouraging data so far, essentially all patients have responded. We see very high rates of MRD negativity. So if we look at PCR for BCR-ABL, the MRD negativity response rate is 87%. We now have even more sensitive MRD tests that are sensitive down to one out of a million cells, that a highly sensitive next-generation sequencing assay is negative in 89% of patients, and we see rapid clearance of the disease within just a week or two of the initial treatment.  

So, importantly, we’ve also only transplanted one out of the 60 patients that we’ve treated so far. So we also believe that this is not only a chemotherapy-free regimen but one that can overcome the need for transplant. 

The initial survival data is very encouraging, we have a two-year survival of 88%, which compares favourably to what we see with intensive chemotherapy, and also what was seen with the dasatinib and blinatumomab. We have seen a few relapses which have tended to be in the central nervous system, so what we’re doing is planning to increase the total number of doses of intrathecal prophylaxis to help prevent that in the future. 

With that said, we’re very encouraged by certainly the response rate, the depth of response, and the durability of these responses, and the study continues to accrue patients. We’re hoping that we can really change the paradigm of treating patients with pH positive ALL, to where we take it from one of the most aggressive subtypes of ALL historically, to now one that we can treat with a chemotherapy-free regimen and also without transplant in first remission.