Current Treatment Protocols for Ph+ ALL Treatment

We have to distinguish between assistential protocols and clinical trials. For assistential protocols in the real world, we are still using first- and second-generation TKI combined with low-intensity chemotherapy, and we follow these patients by [measurable residual disease (MRD)]. Then, the MRD level at 3 months after the initiation of therapy is the perfect moment to indicate the need for allogeneic stem cell transplantation.

Now, clinical trials use third-generation TKIs [and] use immunotherapy, and the panorama has completely changed. Outstanding responses, potent MRD negativity, deep MRD negativity—and then the indication for transplantation in these clinical trials remains marginal. It is important to distinguish what we are dealing with: clinical trials or assistential trials.

The benefit of TKIs and chemotherapy is to provide a high grade of response. The complete cytologic response is over 100%, and the molecular response is about 50% so this is an improvement. This limits the indication of transplantation to the patients who are MRD positive, but we can spare transplantation in those who are MRD negative. This is what occurs in real life.

Now, the advent of chemo[therapy]-free trials, immunotherapy-based trials, third–generation-based trials, improve the response and improve the quality of the response, and all of it is achieved with low-grade toxicity, so that they are feasible at all age groups. This is important for [older patients] in whom Ph-positive ALL is observed in half of ALL patients. It is important that now, the progress has been not only in efficacy, but also in tolerability and availability.