A Multi-site Study to Evaluate the Persistence of Protective Immunity to Routine Childhood Vaccinations in Participants With B-ALL/Ly Who Have Received Blinatumomab

The most common form of malignancy in children is B-cell acute lymphoblastic leukemia (B-ALL). B-ALL is a type of blood cancer resulting from clonal expansion of an abnormal B-cell precursor known as a lymphoblast. Mature normal B-cells are white blood cells produced in the bone marrow that play a crucial role in fighting infections and in humoral immunity. Abnormal, immature B-cells begin to form and multiply quickly, crowding out healthy cells in the bone marrow. As these cancerous B-cells accumulate, they spill into the bloodstream and can spread (metastasize) throughout the body.

CD19 is the antigen expressed on the surface of nearly all B cells throughout all phases of maturation. CD19 expression plays a crucial role in the body's ability to mount an immune response against a pathogen. Through several studies, CD19 was found to be highly conserved among B-cell malignancies, making it an optimal target for B-ALL treatment. Blinatumomab is a bispecific T-cell engager (BiTE) that links the T-cell CD3 and B-cell CD19. This results in the activation, proliferation, and clonal expansion of T-cells resulting in destruction of the targeted CD19+ cells. Blinatumomab has been shown to improve outcomes among pediatric patients diagnosed with B-ALL significantly; and is now a part of the backbone of treatment for B-ALL.

A key concern for the pediatric population receiving blinatumomab is the potential loss of vaccine-induced immunity established before chemotherapy. Intensive chemotherapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) can impair humoral immunity, leading to the loss of antibodies generated by previous vaccinations due to the depletion of memory B cells. Currently, there is no established protocol for revaccination in B-ALL patients treated with blinatumomab. However, prior studies involving other immunotherapeutic agents, such as CAR T-cell therapy, have shown that patients often exhibit low post-treatment antibody titers, necessitating booster doses or even full revaccination. Because blinatumomab has shown to improve outcomes in the vast majority of children with B-ALL, it is critical to determine the unknown long-term effects on humoral immunity in these patients.

Clinical practice regarding revaccination post-chemotherapy in the B-ALL population is widely variable. Children with leukemia who have undergone chemotherapy often experience prolonged immunosuppression, making them particularly vulnerable to vaccine-preventable diseases. The disease itself, combined with its treatment, causes significant immunosuppression-especially in acute lymphoblastic leukemia (ALL)-when compared to solid tumors. While partial immune recovery may occur approximately three months after chemotherapy, full recovery can take longer and depends on factors such as the patient's age, type of cancer, and the intensity of treatment received. In immunocompromised patients, live vaccines are generally considered to be unsafe, putting patients at high risk of viral reactivation. However, non-live (inactivated) vaccines are considered safe and effective. Therefore, it is essential to establish a clear vaccination protocol to protect this vulnerable population from preventable infections.

While standard vaccination practices aim to establish long-term protection against vaccine-preventable diseases, the durability of this immunity following immunotherapy remains unclear. This study will assess whether pediatric patients (less than 21 years old) who have been treated with blinatumomab retain protective antibody titers from their primary childhood vaccinations and whether revaccination restores immune protection. Because the vast majority of B-ALL patients - including B-Lymphoblastic Lymphoma - will receive 2 cycles of blinatumomab during their treatment, understanding the long-term impact of this drug on vaccine-induced humoral immunity is imperative.

The investigators hypothesize that pediatric patients with B-cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (B-ALL/Ly) who have received blinatumomab will not retain protective immunity conferred by the routine childhood primary series of vaccinations and that revaccination will result in a robust serologic response.

Inclusion criteria

• Diagnosis of B-lineage acute lymphoblastic leukemia/lymphoma
• ≥1 year old and up to 21 years old at diagnosis
• Informed consent provided, and if applicable, child assent provided
• Must have received all vaccinations routinely administered during first year of life

Exclusion criteria

• Relapsed/refractory disease at any time
• Received or will require a bone marrow transplant and/or cellular therapy
• Pregnancy