Inotuzumab-ozogamicin (drug) for the treatment of acute lymphoblastic leukemia (ALL) in patients aged 56 and older

Acute lymphoblastic leukemia (ALL) is a form of blood cancer characterized by the excessive production of abnormal white blood cells (blasts) in the bone marrow. These immature cells displace normal blood cells, which can lead to a variety of health problems, including infections, anemia, and increased bleeding. ALL is common in children, but older adults can also be affected. The prognosis for older patients is often poorer than for younger patients. The standard treatment for older patients with ALL often consists of intensive chemotherapy; however, due to side effects and comorbidities, this treatment is not always suitable and often must be discontinued.

The goal of the INITIAL-1 study is to test the efficacy of inotuzumab ozogamicin. This is an antibody that is conjugated to a targeted chemotherapeutic agent (calicheamicin) (antibody-drug conjugate) and is directed against a surface receptor (CD22) on the leukemia cells. Calicheamicin is a highly effective drug that destroys cancer cells. It is already approved for the treatment of ALL in certain situations. All patients receive the same treatment (a single study arm) and are aware of it (open-label). As with all ALL patients, they will first receive pretreatment to prevent side effects; however, no standard chemotherapy is administered before the start of the study. This is followed by three cycles of inotuzumab ozogamicin and a single intrathecal administration. Intrathecal therapy involves the direct treatment of the central nervous system; for this, the medication is injected with a needle into the cerebrospinal fluid space at the base of the spinal canal, which is technically equivalent to a lumbar puncture. Conventional chemotherapy drugs are then used to maintain the treatment’s success (maintenance therapy). The study primarily evaluates event-free survival after one year; this is the time without a disease-related event (e.g., recurrence of blasts in the bone marrow).

Eligible participants are patients who are at least 56 years old and have a new diagnosis of acute lymphoblastic leukemia with a blast count of > 25% in the bone marrow. Patients must not have received any prior specific ALL therapy, and they must be ineligible for conventional intensive therapy due to their age (> 75 years) or other medical conditions (in which case, age > 56 years). The CD22 receptor, which is specifically targeted by the study drug, must be present on at least 20% of the leukemia cells. The study will run for several years, during which patients will be monitored regularly for treatment response and any side effects.