A More Targeted Approach to Leukemia: Less Chemotherapy, More Immunotherapy for Children and Adolescents with Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a form of blood cancer that affects lymphocytes, a subtype of white blood cells. It occurs most frequently in children and adolescents. In this condition, the bone marrow produces a large number of abnormal, immature lymphocytes that displace normal blood cells and weaken the immune system. The disease progresses rapidly and therefore requires immediate treatment. The standard treatment for ALL consists of intensive chemotherapy, followed by a stem cell transplant if necessary. Chemotherapy is administered according to well-established treatment protocols. However, advances in the ability to analyze ALL cells have shown that there are significant differences within ALL in terms of the characteristics of the ALL cells. Therefore, affected patients could benefit from more personalized therapy tailored to the specific characteristics of their own ALL cells.

The AIEOP-BFM ALL 2017 study specifically uses new drugs to improve the treatment of children and adolescents with acute lymphoblastic leukemia (ALL). One of these drugs is blinatumomab, a so-called bispecific antibody. It directly links certain immune cells (T cells) to the leukemia cells, enabling the body’s own immune system to specifically target and destroy the cancer cells—without the need for conventional chemotherapy. This immunotherapy is being tested particularly in patients who are at high risk of relapse or who respond poorly to standard therapy.

Another drug is bortezomib, which is used in certain cases in addition to chemotherapy. It blocks an important protein degradation pathway in leukemia cells, making them more susceptible to treatment—especially when they are resistant to conventional drugs. The goal of these approaches is to improve the chances of cure while reducing the side effects of therapy.

The goal of the AIEOP-BFM ALL 2017 study (Phase 3 study) is to investigate the efficacy and safety of the various treatment protocols based on individual relapse risk. The individual risk of ALL recurrence after treatment is determined as part of the study through a comprehensive initial evaluation. After initial treatment, patients are assigned to different risk groups based on genetic characteristics, their response to therapy, and minimal residual disease (MRD). These groups then receive specific treatment plans tailored to their risk of relapse.

Patients with a particularly high risk even in the early stages receive the drug bortezomib in addition to standard therapy; this is intended to make the cancer cells more sensitive to treatment. A new approach is being tested in the high-risk group: Instead of additional intensive chemotherapy cycles, immunotherapy with blinatumomab is used to reduce the burden of treatment and specifically target resistant leukemia cells. Children and adolescents with a moderate risk of relapse receive an additional cycle of blinatumomab following a more intensive phase of chemotherapy to further lower the risk of relapse. For T-cell ALL patients who do not belong to the high-risk group but do not respond optimally to the first line of therapy, the second phase of treatment is extended and the dosage increased to eliminate as many cancer cells as possible.

The goal of these differentiated treatment approaches is to make treatment more individualized and targeted: more aggressive for high-risk patients, gentler for those with a good prognosis—always with the aim of increasing the chances of a cure and reducing long-term side effects.

The treatments and follow-up examinations as part of the study will continue for up to 10 years, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be monitored. A key factor is whether or when the disease recurs during therapy.

Patients with previously untreated acute lymphoblastic leukemia (ALL) or MPAL (in which the cancer cells exhibit characteristic features of different cell types), diagnosed before the age of 18, are eligible to participate in this study.