# Therapeutic Antibodies in Hematology: Advances in Malignant and Non-Malignant Disorders

## TL;DR

Therapeutic antibodies have transformed the treatment of blood disorders, offering new options for both cancers and non-cancer conditions, but challenges like toxicity and resistance remain.

## Contribution

The paper reviews recent advances in therapeutic antibody formats and engineering strategies for hematological disorders, highlighting new formats like T-cell–redirecting bispecific antibodies.

## Key findings

- Therapeutic antibodies have improved survival in hematologic malignancies through targets like CD20, CD19, CD38, and BCMA.
- Complement inhibitors like eculizumab and bispecific antibodies like emicizumab have redefined treatment for non-malignant disorders.
- Trifunctional antibodies like Tri-31C2 show enhanced anti-myeloma activity compared to traditional CD38 antibodies.

## Abstract

What are the main findings?
Therapeutic antibodies, including monoclonal antibodies, antibody–drug conjugates, and bispecific antibodies, have fundamentally transformed the treatment of both malignant and non-malignant hematologic disorders.Advances in antibody engineering, such as T-cell–redirecting bispecific antibodies and structure-guided optimization, have expanded therapeutic efficacy but also revealed new challenges, including treatment-related toxicity and antigen escape.

Therapeutic antibodies, including monoclonal antibodies, antibody–drug conjugates, and bispecific antibodies, have fundamentally transformed the treatment of both malignant and non-malignant hematologic disorders.

Advances in antibody engineering, such as T-cell–redirecting bispecific antibodies and structure-guided optimization, have expanded therapeutic efficacy but also revealed new challenges, including treatment-related toxicity and antigen escape.

What is the implication of the main finding?
Future antibody-based therapies in hematology will require integrated strategies that balance efficacy and safety by addressing cytokine-related toxicities, off-target effects, and resistance mechanisms.Rational multi-antigen targeting, supported by structural prediction and molecular profiling, is expected to enhance the durability and precision of next-generation immunotherapies.

Future antibody-based therapies in hematology will require integrated strategies that balance efficacy and safety by addressing cytokine-related toxicities, off-target effects, and resistance mechanisms.

Rational multi-antigen targeting, supported by structural prediction and molecular profiling, is expected to enhance the durability and precision of next-generation immunotherapies.

Therapeutic antibodies have revolutionized hematology, offering targeted and effective treatments for both malignant and non-malignant diseases. In hematologic malignancies, anti-CD20, anti-CD19, anti-CD38, and anti–B-cell maturation antigen (BCMA) antibodies have markedly improved survival outcomes, whereas antibody–drug conjugates and bispecific antibodies continue to expand therapeutic possibilities. Besides cancer, complement inhibitors such as eculizumab, ravulizumab, and the recently approved crovalimab have redefined paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome management, and the bispecific antibody emicizumab has transformed prophylaxis in hemophilia A. Furthermore, novel antibody formats such as the trifunctional anti-CD38 × CD3 antibody (Tri-31C2) exhibit enhanced anti-myeloma activity compared to chimeric CD38 antibodies, underscoring the future potential of T-cell–redirecting designs. This review summarizes key developments in therapeutic antibodies for hematological disorders, their action mechanisms, and emerging strategies to further optimize their efficacy and safety.