What is the treatment for B-cell acute lymphoblastic leukemia (B-ALL) with anti-CD22 therapy?

From the Guidelines

Inotuzumab ozogamicin is the recommended anti-CD22 therapy for adults with relapsed and/or refractory CD22-positive B-cell precursor ALL, due to its high affinity for CD22 and ability to induce DNA strand cleavage and cell death. The treatment approach for B-cell acute lymphoblastic leukemia (B-ALL) has evolved with the introduction of targeted therapies, particularly anti-CD22 agents. Inotuzumab ozogamicin (InO) is a humanized anti-CD22 monoclonal antibody conjugated to a derivative of the cytotoxic agent calicheamicin, which is released intracellularly and induces DNA strand cleavage, leading to cell death mediated through calicheamicin-induced apoptosis 1. Some key points to consider when using InO include:

• The impact of CD22 inhibition on immunity is unclear, as CD22 regulates multiple B cell functions, but its role in protection against pathogens is not well established 1.
• In clinical trials, InO has been associated with a lower incidence of febrile neutropenia, sepsis, and septic shock compared to standard therapy 1.
• However, the combination of InO with low-intensity chemotherapy (mini-hyper-CVD) has been linked to a higher rate of infections 1.
• Monitoring of the QT interval is essential when using InO, as it can prolong the QT interval and increase the risk of Torsades de pointes 1. Overall, the use of InO as an anti-CD22 therapy for B-ALL offers a promising treatment approach, but it is crucial to carefully evaluate the benefits and risks, particularly in terms of infectious complications and cardiac effects 1.

From the FDA Drug Label

BESPONSA is a CD22-directed antibody and cytotoxic drug conjugate indicated for the treatment of relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older. BESPONSA is indicated for the treatment of relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older. BESPONSA is a CD22-directed antibody and cytotoxic drug conjugate indicated for the treatment of relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older.

Inotuzumab ozogamicin (IV) is used to treat relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older 2, 2, 2.

• The drug is a CD22-directed antibody and cytotoxic drug conjugate.
• It is indicated for patients with CD22-positive B-cell precursor ALL who have relapsed or are refractory to other treatments.

From the Research

Anti-CD22 B-ALL Treatment

• The treatment of B-cell acute lymphoblastic leukemia (B-ALL) has seen significant improvements in recent years, with the introduction of novel therapies such as inotuzumab ozogamicin (InO) 3.
• InO is an antibody-drug conjugate that targets CD22, a protein expressed on the surface of B-ALL cells, and has shown high response rates in clinical trials 4, 3.
• A phase 1 dose-escalation trial of InO in combination with dose-adjusted EPOCH (DA-EPOCH) chemotherapy in adults with relapsed or refractory B-ALL found that the combination was feasible and had high response rates, with a morphologic complete response rate of 84% 4.
• Another study found that InO was superior to standard of care regimens in patients with relapsed or refractory B-ALL, with a significantly improved complete remission rate of 80.7% compared to 29.4% for chemotherapy 3.

Patient Outcomes

• The overall survival rate for adults with B-ALL has improved significantly with the introduction of new therapies, with a median overall survival of 17.0 months in one study 4.
• However, the prognosis for patients who progress after CD19 chimeric antigen receptor (CAR) T-cell therapy is poor, with a median survival of 7.5 months after progression 5.
• A subset of patients who received salvage treatment after progressing after CAR T-cell therapy achieved sustained remissions, including those who received blinatumomab and/or InO 5.

Future Directions

• Ongoing trials are investigating the combination of InO with other agents in the relapse setting and the addition of InO to frontline therapy 3.
• Novel therapeutic strategies are needed to reduce the risk of progression after CAR T-cell therapy and improve outcomes for patients with B-ALL 5.
• Further research is also needed to understand the effects of specific disease and patient characteristics on long-term outcomes with each of the FDA-approved agents for B-ALL 6.