Frontline ponatinib plus blinatumomab for Ph+ ALL

In this video, Prof Robin Foà, emeritus professor of haematology at the Sapienza University of Rome discusses two abstracts presented at ASH zooming in on the use of ponatinib plus blinatumomab as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL).

Over the last decade, the development of next generation tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL fusion gene revolutionized the treatment of Ph+ ALL. More recently, also the introduction of blinatumomab in the treatment paradigm for these patients has led to improved outcomes. Building on these two success stories, several studies are currently exploring combinations of a BCR-ABL TKI and blinatumomab. 

In the Gimema ALL2820 study, 133 newly diagnosed adult Ph+ ALL patients were treated with a steroid pre-phase followed by a 70-day induction with ponatinib followed by at least 2 cycles (maximum 5) of blinatumomab. By the end of the induction phase, 96% of these patients had obtained a complete hematologic remission (CHR). After 2 cycles of blinatumomab, an overall molecular response rate of 74% was reported. At the 1-year landmark, 94.6% of patients was still alive, with a corresponding 1-year disease-free survival (DFS) rate of 95.6%. Importantly, these high response rates did not come at the cost of excessive toxicity, with a low rate of treatment discontinuation across the age spectrum. Allogenic stem cell transplant (alloSCT) allocation was based on the IKZFplus profile at presentation and the persistence of minimal residual disease (MRD). At the time of the analysis, this approach led to an alloSCT in only 14.5% of patients. This indicates that the ponatinib-blinatumomab regimen can effectively spare Ph+ ALL patients from the burden of chemotherapy and an alloSCT.1 

A second presentation that was discussed by Dr Foà looked at the immunomodulatory effects of dasatinib and ponatinib when used in combination with blinatumomab. This analysis revealed that a frontline treatment with dasatinib and blinatumomab induces a more profound NK, T-NK and Treg immune modulation than what was seen with ponatinib plus blinatumomab.2 However, whether these differences in immunomodulation also lead to a different disease control with both regimens remains unclear and requires longer follow-up.