Acute myeloid leukemia: We are moving from the era of standard chemotherapy to precision medicine

How big a therapeutic challenge is refractory and relapsed acute myeloid leukemia?

The treatment of refractory relapsed acute myeloid leukemia is an ongoing unresolved medical need, for the reason that the prognosis of relapsed patients is unfortunately poor. The prerequisite for prolonging survival is to achieve a second complete remission, which is already a hassle, and then qualify the patient for allogeneic transplantation. And even in spite of such aggressive treatment, long-term survival in these patients is in the 20-25 percent range (patients survive 4 to 5 years).

And how has the picture of diagnosing and treating acute myeloid leukemia changed over the past few years, including with FLT3 mutation?

We are living in very interesting times, when we are moving from the era of standard chemotherapy, where one type of treatment is used for all acute myeloid leukemia patients, to a highly personalized approach. We are talking about so-called precision medicine, personalized and tailored to the genetic profile of patients. The presence of FLT3 mutations in patients with acute leukemia is always associated with an unfavorable prognosis, both de novo, and in the case of relapse, treatment outcomes are very poor. In the last decade, there has undoubtedly been a huge breakthrough in the treatment of acute myeloid leukemia, especially after the introduction of new targeted therapies that can act on various signaling pathways leading to the development of acute myeloid leukemia. And here we should emphasize the great role of FLT3 kinase inhibitors. The addition of precisely these inhibitors both in the first line (such as midostaurin) and, for example, the use of these inhibitors in relapsed acute myeloid leukemia has dramatically improved the prognosis in this group of patients.

What is the therapeutic range in this group of patients today?

The choice of treatment and therapeutic options depend on two factors: the patient's age, general condition and comorbidities. Young patients in good general condition, so-called fit patients, are candidates for intensive and aggressive treatment with the intention of cure. For these patients, in induction treatment, i.e. first-line treatment to achieve remission, we use intensive chemotherapy in combination with an FLT3 inhibitor, precisely with midostaurin, which is registered and available under the drug program. On the other hand, for unfit patients, that is, those who are not eligible for standard chemotherapy, unfortunately we do not yet have a registered inhibitor that we can add to standard treatment. As a result, we only have the standard therapeutic option venetoclax with azacitidine. We already know that in these patients, also more often than in the average population, relapses follow this treatment. In contrast, for patients with refractory relapsed myeloid leukemia, we have a second-generation FLT3 inhibitor at our disposal. This is gilteritinib, a drug registered for the treatment of this group of patients, interestingly in both the fit and unfit populations. The results of a large randomized trial confirmed that monotherapy with the oral form of the inhibitor, just gilteritinib, is associated with a higher remission rate and longer overall survival, a higher percentage of patients we can qualify and offer them allogeneic transplantation, compared to these two standard therapeutic options, that is, chemotherapy both intensive and not. So we actually have a very good tool at the moment, and we are using it in clinical practice with great success.